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BACKGROUND: The etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. OBJECTIVE: The aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. METHODS: Standardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. RESULTS: In the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. CONCLUSION: Our results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.

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Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ovalbúmina , ARN Ribosómico 16S , Sistema Respiratorio , Rinitis Alérgica , Linfocitos T Reguladores , Células TH1 , Células Th2 , Animales , Ratones , Microbioma Gastrointestinal/inmunología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Rinitis Alérgica/inmunología , Rinitis Alérgica/microbiología , Células TH1/inmunología , Ovalbúmina/inmunología , ARN Ribosómico 16S/genética , Sistema Respiratorio/microbiología , Sistema Respiratorio/inmunología , Femenino , Ratones Endogámicos BALB C , Citocinas/metabolismo , Interleucina-10/genética , Inmunoglobulina E/sangre , Heces/microbiología , Líquido del Lavado Nasal/inmunología , Líquido del Lavado Nasal/microbiología , Interferón gamma/genética , Interleucina-4

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BACKGROUND: Posterior fossa malformation (PFM) is a relatively uncommon prenatal brain malformation. Genetic diagnostic approaches, including chromosome karyotyping, copy number variant (CNV) testing, and whole-exome sequencing (WES), have been applied in several cases of fetal structural malformations. However, the clinical value of appropriate genetic diagnostic approaches for different types of PFMs has not been confirmed. Therefore, in this study, we aimed to analyze the value of different combined genetic diagnostic approaches for various types of fetal PFMs. METHODS: This retrospective study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital. Fifty-one pregnant women diagnosed with fetal PFMs who underwent genetic testing in our hospital from January 1, 2017 to December 31, 2022 were enrolled; women with an isolated enlarged cisterna magna were excluded. All participants were categorized into two groups according to the presence of other abnormalities: isolated and non-isolated PFMs groups. Different combined approaches, including karyotype analysis, CNV testing, and trio-based WES, were used for genetic analysis. The detection rates of karyotype analysis, CNV testing, and WES were measured in the isolated and non-isolated groups. RESULTS: In isolated PFMs, pathogenic/likely pathogenic (P/LP) CNVs were detected in four cases (36.36%, 4/11), whereas G-banding karyotyping and WES showed negative results. In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); karyotyping revealed aneuploidies in five cases (16.67%, 5/30), CNV testing showed P/LP CNVs in five cases (16.13%, 5/31), and WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22). WES showed a detection rate of 83.33% (5/6) in fetuses with Joubert syndrome. Only six patients (five with Blake's pouch cyst and one with unilateral cerebellar hemisphere dysplasia) survived. CONCLUSIONS: We recommend CNV testing for fetuses with isolated PFMs. A sequential genetic approach (karyotyping, CNV testing, and WES) may be beneficial in fetuses with non-isolated PFMs. Particularly, we recommend WES as the first-line genetic diagnostic tool for Joubert syndrome.

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Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Cariotipificación , Diagnóstico Prenatal , Humanos , Femenino , Variaciones en el Número de Copia de ADN/genética , Embarazo , Cariotipificación/métodos , Secuenciación del Exoma/métodos , Diagnóstico Prenatal/métodos , Adulto , Estudios Retrospectivos , Pruebas Genéticas/métodos , Fosa Craneal Posterior/anomalías

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Objective: Based on machine learning method, four types of early postoperative frailty risk prediction model of enterostomy patients were constructed to compare the performance of each model and provide the basis for preventing early postoperative frailty of elderly patients with enterostomy. Methods: The prospective convenience sampling method was conducted and 362 early postoperative enterostomy patients were selected in three hospitals from July 2020 to November 2023 in Shanghai, four different prediction models of Support Vector Machine (SVM), Bayes, XG Boost, and Logistic regression were used and compared the test effects of the four models (MCC, F1, AUC, and Brier index) to judge the classification performance of the four models in the data of this study. Results: A total of 21 variables were included in this study, and the predictors mainly covered demographic information, stoma-related information, quality of life, anxiety and depression, and frailty. The validated models on the test set are XGBoost, Logistic regression, SVM prediction model, and Bayes on the MCC and F1 scores; on the AUC, XGBoost, Logistic regression, Bayes, and SVM prediction model; on the Brier scores, Bayes, Logistic regression, and XGBoost. Conclusion: XGBoost based on machine learning method is better than SVM prediction model, Logistic regression model and Bayes in sensitivity and accuracy. Quality of life in the early postoperative period can help guide clinical patients to identify patients at high risk of frailty and reduce the incidence of early postoperative frailty in elderly patients with enterostomy.

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Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.

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Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.

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Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

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Objective To investigate the diagnostic value of diffusion weighted imaging(DWI)-based radiomics model to identify small hepatocellular carcinoma(＜2 cm)(SHCC)and dysplastic nodule(DN)in the background of hepatitis cirrhosis.Methods A total of 93 cases SHCC and 25 cases with DN with complete enhanced MRI images and surgically pathologically confirmed were collected retrospectively.Chi-square test was performed to analyze the signal characteristics of DWI and enhanced triphasic MRI images between the two groups.ITK-SNAP was used to draw the region of interest(ROI)on DWI,and FAE software was applied for extraction,selec-tion,and construction of support vector machine(SVM)models(dividing into training set and test set according to the ratio of 7∶3).The diagnostic performance of model was evaluated by receiver operating characteristic(ROC)curve.Results There were statisti-cally significant differences in enhanced triphasic MRI and DWI between SHCC and DN(P＜0.05).The area under the curve(AUC)of the DWI-SVM model training set was 0.936,and sensitivity,specificity and accuracy was 95.4％,88.2％and 93.9％,respec-tively,and the AUC of the test set was 0.911,and sensitivity,specificity and accuracy was 85.7％,87.5％and 86.1％,respectively,which were all significantly better than the diagnostic efficacy of DWI(AUC=0.720).Conclusion DWI-SVM model with signifi-cantly higher AUC and specificity can effectively differentiate SHCC from DN in the background of hepatitis cirrhosis.

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Objective:To select and obtain relevant evidence on the prevention and management of gastric retention in premature infants, so as to form the best summary of evidence.Methods:According to the "6S" evidence model system, we searched the domestic and foreign evidence-based databases, relevant guide websites, and association websites for all literature on the prevention and management of gastric retention in premature infants, including clinical decisions, guidelines, best practice information books, evidence summaries, systematic evaluations, and expert consensus. The search period was from January 1, 2013 to June 8, 2023.Results:A total of 12 articles were included, including 5 guidelines, 1 recommended practice, 5 systematic reviews, 1 expert consensuses. A total of 20 pieces of best evidence were collected, mainly involving 6 aspects of feeding management, placement of gastric tube, position management, gastric residue monitoring, gastric residue treatment, intervening measure.Conclusions:This study summarized the best evidence for the prevention and management of gastric retention in premature infants, so as to provide theoretical basis for clinical management of gastric retention and promote the establishment of enteral nutrition in premature infants.

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ObjectiveTo investigate the clinical effect and possible mechanism of modified Shenling Baizhu Powder （参苓白术散） and Xiaoluo Pill （消瘰丸） in the treatment of children with adenoid hypertrophy due to spleen deficiency and phlegm accumulation. MethodsOne hundred and thirty children with adenoid hyperplasia due to spleen deficiency and phlegm accumulation were randomly divided into 65 cases each in the observation group and control group. The control group was given mometasone furoate nasal spray， one spray into each nostril， once a day， while the observation group was given modified Shenling Baizhu Powder and Xiaoluo Pill orally， one dose per day， and both groups were treated for 8 months. The pre- and after-treatment electronic nasopharyngoscope scores， specific quality of life survey scale （OSA-18） scores， total TCM symptom scores， serum cysteine leukotrienes （CysLTs）， interleukin 2 （IL-2）， tumor necrosis factor α （TNF-α）， and interleukin 10 （IL-10） levels were compared to determine the clinical efficacy after treatment. ResultsAfter treatment， the electronic nasopharyngoscope scores， OSA-18 scores， total TCM symptom scores， serum CysLTs， IL-2 and TNF-α levels significantly decreased， while IL-10 levels increased in both groups （P＜0.01）. Compared between the two groups after treatment， the electronic nasopharyngoscope score， OSA-18 score， total TCM symptom score， serum CysLTs， IL-2 and TNF-α levels were significantly lower， and the IL-10 level was higher in the observation group than in the control group （P＜0.01）. The total effective rate of the observation group was 95.38% （62/65）， superior to 81.54% （53/65） of the control group （P＜0.05）. ConclusionFor children with adenoid hypertrophy due to spleen deficiency and phlegm accumulation， modified Shenling Baizhu Powder and Xiaoluo Pill can help to improve symptoms， increase quality of life and clinical efficacy， and its mechanism may be related to reducing the inflammatory response.

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AIM: To analyze the changes of the dominant eye in myopic patients after small incision lenticule extraction(SMILE)and its effect on visual quality.METHODS: Prospective clinical study. A total of 140 patients(280 eyes)who underwent SMILE operation to correct myopia in the First Affiliated Hospital of Xinjiang Medical University from June to December 2022 were selected. They were divided into dominant eye transformation group(46 cases, 92 eyes)and non-transformation group(94 cases, 188 eyes)according to whether the dominant eye transformation occurred during the follow-up in postoperative 3 mo. The uncorrected visual acuity(UCVA)of the two groups was evaluated, the subjective visual quality was evaluated by the quality of life impact of refractive correction(QIRC)scale, and the objective visual quality was evaluated by measuring the high-order aberrations of the whole eye before and at 1 and 3 mo after surgery.RESULTS: Before SMILE, the right type of dominant eye was 105 cases, left-type was 35 cases. There were 46 cases had change at 1 mo postoperatively, and there was no new change at 3 mo after operation than 1 mo after operation. There was no significant difference in UCVA and QIRC scale score between the two groups preoperatively and at 1 and 3 mo postoperatively(P&#x003E;0.05). Comparison of the dominant eye between the two groups: the total higher-order aberrations and spherical aberrations at 3 mo postoperatively were significantly higher than those in the non-transformed group(P=0.030, 0.046); Comparison of the non-dominant eye between the two groups: trefoil in the transformed group at 1 mo postoperatively was significantly higher than that in the non-transformed group(P=0.008). The binocular difference of trefoil in the transition group was significantly higher than that in the non-transition group at 1 mo after surgery(P=0.022), with no differences in the rest parameters.CONCLUSION: Some patients may experience a change in the dominant eye after SMILE surgery, with no significant impact on subjective visual quality. The decrease of objective visual quality in the early postoperative period may be an associated factor in the dominant eye transformation.

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AIM:To measure the superficial capillary plexus(SCP)vessel density(VD), deep capillary plexus(DCP)VD, and the area, circumference, and roundness index of the foveal avascular zone(FAZ)in healthy individuals of four ethnic groups, namely, Uyghur, Han, Kazakh, and Hui by optical coherence tomography angiography(OCTA), and to investigate the differences of blood flow parameters in macular area of healthy individuals among different ethnic groups in China.METHODS: A total of 80 cases(80 eyes)of healthy subjects if each of the four ethnic groups who went to the Eye Center of the Friendship Hospital of Ili Kazak autonomous Prefecture from December 2022 to March 2023 and met the criteria were selected for the study, with 320 eyes totally. The patients were grouped and numbered according to their ethnicity, and the spherical equivalent and axial length were obtained by using an autorefractor and IOL Master. The blood flow images of the macular area in the range of 3 mm×3 mm were obtained by using a DRI Triton OCT detector, and the images were analyzed by using the built-in IMAGENET6 software to obtain the blood flow parameters. Furthermore, the differences in the blood flow parameters between different ethnic groups as well as the effects of gender, age, and axial length on macular blood flow parameters of different ethnic groups were compared.RESULTS:There were no statistically significant differences in gender, age, axial length, diopter, and image quality(IQ)among the four groups of subjects(all P&#x003E;0.05). Ethnic differences: in SCP, Uyghur inferior VD is higher than Kazakh, Hui inferior VD is higher than Han and Kazakh, Han and Hui nasal VD is higher than Uyghur, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area is smaller than the other 3 ethnic groups, Han and Hui FAZ perimeter is larger than Kazakh, and Hui FAZ circularity index is lower than the other 3 ethnic groups; in DCP, Uyghur foveal VD is higher than Han and Hui, Kazakh foveal VD is higher than Han and Hui, Kazakh FAZ area and perimeter are smaller than the other 3 ethnic groups and Kazakh FAZ circularity index is higher than the other 3 ethnic groups(all P&#x003C;0.05). Sex differences: in SCP, FAZ area and perimeter of Han females were larger than those of males, and FAZ circularity index of Hui females was higher than that of males(all P&#x003C;0.05); in DCP, parafoveal VD and whole VD in females of all four ethnic groups were higher than those of males(all P&#x003C;0.05). Age correlation: in SCP, age was negatively correlated with the FAZ circularity index of Kazakh; in DCP, age was negatively correlated with the parafoveal and the whole VD of Han, Kazakh, and Hui(all P&#x003C;0.05). Axial length correlation: in SCP, the axial length was negatively correlated with Kazakh and Hui foveal VD, Hui parafoveal VD, Uyghur, Kazakh and Hui whole VD, and positively correlated with Kazakh FAZ area and perimeter; in DCP, the axial length was negatively correlated with Uyghur, Kazakh, Hui foveal VD, Hui whole VD, and positively correlated with Kazakh and Hui FAZ area and perimeter(all P&#x003C;0.05).CONCLUSION:There were differences in macular blood flow parameters among the Uyghur, Han, Kazakh, and Hui populations, with the area and perimeter of the FAZ of the Kazakh significantly smaller than those of the other three ethnic groups. Gender, age, and axial length are also related to macular blood flow parameters.

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Objective: To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

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Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Acidosis , Carnitina , Estudios Retrospectivos , Espectrometría de Masas en Tándem

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Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

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Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

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Objective To study the status of diabetic foot and its related factors in Hanzhong area in recent years, and to provide a scientific basis for the prevention and management of diabetic foot complicated by type 2 diabetes. Methods A stratified sampling method was used to select 528 patients with type 2 diabetes among permanent residents in Hanzhong from April 2016 to April 2022. Relevant medical history and laboratory examination data were collected, and the incidence of diabetic foot was calculated. The influence of related factors on the risk of diabetic foot was analyzed by regression model. Results Among 528 subjects in this study, the disease course and body type of T2DM showed that male patients had significantly longer disease, and the proportion of overweight and obesity was higher, P2=27.516，P<0.05）. The proportion of male patients complicated with diabetic foot was higher than that of female patients (P<0.05). At the same time, the incidence of Wagner Grade I was higher in males than in females (P<0.05). The effects of potential factors on the risk of diabetic foot were discussed by gender. Univariate analysis and multivariate logistic regression analysis indicated that the risk factors of diabetic foot in male T2DM patients included: Increased course of disease, increased age, poor blood glucose control, increased total cholesterol level, increased BMI level and increased platelet to lymphocyte ratio . Potential risk factors in women include increased course of disease, age, poor blood sugar control (increased glycosylated hemoglobin levels) and increased platelet to lymphocyte ratios in all cases（P<0.05）. Conclusion The current prevalence rate of type 2 diabetes patients complicated with diabetes foot in Hanzhong area is 16.29%, which is still high , and the prevalence rate of men is significantly higher than that of women. Older age, long duration of T2DM, poor blood glucose control, increased total cholesterol level, increased blood uric acid level, decreased urine pH value, and increased platelet lymphocyte ratio are potential risk factors for diabetes foot. Male patients should also pay attention to the occurrence of overweight and obesity tendency to reduce the risk of diabetes foot.

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Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

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Objective:To explore the protective effect of 18α glycyrrhetinic acid (18α-GA) on acute ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice, providing theoretical and experimental basis for the clinical application of 18α-GA.Methods:Forty male C57BL/6J mice were randomly divided into 5 groups: DSS model group, positive drug control group, high, medium, and low dose groups of 18α-GA, with 8 mice in each group. The 5 groups of mice were continuously fed with 3% DSS solution for 7 days to establish an acute UC animal model. At the same time, each group was intraperitoneally injected with 100 mg/kg physiological saline, 100 mg/kg sulfasalazine, 40 mg/kg 18α-GA, 20 mg/kg 18α-GA, and 10 mg/kg 18α-GA daily. The weight of mice was measured and recorded daily, and the Disease Activity Index (DAI) of mice was evaluated. On the 8th day, the mice were euthanized and their colon length was measured; After slicing, the colon mucosa was observed and pathological scoring was performed; Western blot was used to detect the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway related proteins in colon tissue; Enzyme linked immunosorbent assay (ELISA) was used to determine the content of interleukin(IL)-1β in colon tissue.Results:Compared with the DSS model group, the weight loss amplitude of the 18α-GA high and medium dose groups was significantly smaller on the 7th day (all P<0.05); Colon length was longer (all P<0.05), the pathological score of colon mucosa was significantly lower (all P<0.05); The expression of GSDMD, cleaved caspase1, and IL-1β in colon tissue was significantly lower (all P<0.05); The 18α-GA high-dose group had lower DAI scores ( P<0.05); The expression of NLRP3 was lower in colon tissue ( P<0.05). Conclusions:18α-GA can improve DSS induced acute ulcerative colitis in mice by inhibiting the activation of NLRP3 inflammasome pathway.

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@#Objective To observe the effect of Cardamonin(CDN)on pulmonary fibrosis in mice,and explore the effect of CDN on transforming growth factor-β1(TGF-β1)/Smad signaling pathway.Methods The mice were grouped into:Sham group,Bleomycin(BLM)group,low dose of Cardamonin(CDN-L)group,medium dose of Cardamonin(CDN-M)group,high dose of Cardamonin(CDN-H)group and Dexamethasone(DXM)group.Injectioning of BLM induce pulmonary fibrosis in mice,the lung index was measured.Enzyme-linked immunosorbent assay kit measured serum tumor necrosis factor-α(TNF-α)levels,the hydroxyproline(HYP)content in lung tissue was detectioned by kits.Pathological changes were observed by Htoxylin Eosin and Masson staining,and the level of genes related to TGF-β1/smad signaling pathway was detected by RT-PCR.Results Compared with the Sham group,the lung index,Szapiel score and Ashcroft score of the BLM group were significantly increased(P<0.05),and the degree of pulmonary inflammation and fibrosis was more severe.The levels of TNF-α in serum and HYP in lung tissue were increased(P<0.05),lung tissue TGF-β1[(1.02±0.21)vs.(3.25±0.14)],smad2[(1.00±0.05)vs.(1.59±0.20)],smad3[(1.00±0.06)vs.(1.59±0.20)],α-smooth muscle actin(α-SMA)[(1.00±0.10)vs.(2.15±0.10)and E-Cadherin[(1.01±0.16)vs.(0.57±0.09)]mRNA level decreased(P<0.05).The intervention of CDN-M and CDN-H could decrease the lung index,alleviate the inflammation and Pulmonary fibrosis,and decrease the levels of TNF-α and HYP(P<0.05).The expression of TGF-β1,smad2,smad3 and α-SMA in lung tissue of mice with pulmonary fibrosis was down-regulate.CDN-L had no significant effect,while CDN-H had similar effects to DXM.Conclusion Cardamonin may play an anti-fibrotic role by mediating epithelial-mesenchymal transition through the TGF-β1/Smad pathway.

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Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.

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ATG8-binding proteins play a key role in autophagy, selective autophagy or non-autophagy process by interacting between ATG8 and the ATG8-interacting motif (AIM) or the ubiquitin-interacting motif (UIM). There is great progress of ATG8-binding proteins in yeast and mammalian studies. However, the plant domain is still lagging behind. Therefore, the structure characteristics of plant ATG8 binding protein were firstly outlined. Unlike the single copy of ATG8 gene in yeast, many homologous genes have been identified in plant. The LIR/ AIM-docking site (LDS) of ATG8 protein contains W and L pockets and is responsible for binding to AIM. The ATG8 protein binds to UIM-containing proteins via UIM-docking site (UDS) instead of LDS. UDS is in the opposite position to LDS, so the ATG8 can bind both AIM and UIM proteins. Secondly, the structure and function of ATG8-binding proteins, especially the selective autophagy receptors, were systematically described. The protein NBR1 and Joka2, as proteaphagy receptors, guide ubiquitination protein aggregates to autophagosome for degradation by binding to AIM and ATG8 in Arabidopsis and tobacco, respectively. AtNBR1 also promotes plant immunity by binding the capsid protein of cauliflower mosaic virus and silencing suppressor HCpro of turnip mosaic virus, mediating pathogen autophagy. AtNBR1 still degrades chloroplast by microautophagy under photoinjure or chlorophagy during ibiotic stress. And the protein ORM mediates the degradation of plant immune receptor flagellin sensing 2 (FLS2) through AIM binding to ATG8. Interestingly, ATI1 and ATI2 participate in both chlorophagy and ERphagy. Otherwise, ER membrane protein AtSec62, soluble protein AtC53, and ubiquitin-fold modifier1-specific ligase 1 (UFL1) can be directly bound to ATG8 as ER autophagy receptors. As pexophagy receptor, AtPEX6 and AtPEX10 bind to ATG8 via AIM and participate in pexophagy. RPN10, as a 26S proteasome subunit, whose C-terminal UIM1 and UIM2 bind ubiquitin and ATG8, respectively, mediates the selective autophagy degradation of 26S proteasome inactivation when fully ubiquitinated. Plant-specific mitochondrial localization proteins FCS-like zinc finger (FLZ) and friendly (FMT) may also be mitophagy receptors. CLC2 binds to ATG8 via the AIM-LDS docking site and is recruited to autophagy degradation on the Golgi membrane. The tryptophan-rich sensory protein (TSPO) in Arabidopsis was involved in clearing free heme, porphyrin and plasma membrane intrinsic protein 2;7 (PIP2;7) through the combination of AIM and ATG8. The conformation of GSNOR1 changes during anoxia, exposing the interaction between AIM and ATG8, leading to selective degradation of GSNOR1. At last, the ATG8 binding proteins involved in autophagosome closure, transport and synthetic synthesis was summarized. For example, plant-specific FYVE domain protein required for endosomal sorting 1 (FREE1) is involved in the closure of autophagosomes during nutrient deficiency. Therefore, according to the recent research advances, the structure and function of plant ATG8-binding proteins were systematically summarized in this paper, in order to provide new ideas for the study of plant selective autophagy and autophagy.