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Objective: To analyze the clinical characteristics of asthmatic children with persistent airflow limitation (PAL) in order to improve understanding of PAL and improve asthma management. Methods: The clinic data of asthmatic children aged 6 to 18 years with and without PAL, who visited the Department of Allergy at Children's Hospital of the Capital Institute of Pediatrics between January 2021 and June 2023, were analyzed retrospectively. The study included a total of 197 patients (153 males and 44 females), with a median age of 9.0 (7.0, 12.0) years. The analysis encompassed demographic features, disease-related factors, laboratory tests, and spirometry parameters. Quantitative data differences between the two groups were assessed using the Student's t-test or the Mann-Whitney U test. Qualitative data comparisons were made using the Chi-square test or Fisher's exact test. Results: This study included 100 non-PAL and 97 PAL patients. The female-to-male ratio in the two groups was 27/73 and 17/80, respectively. Age and BMI were 11.0 (10.0, 13.0) years and 20.3 (17.7, 24.1) kg/m2 in the PAL group, which was significantly higher than in the non-PAL group (P<0.001). Among the PAL group, 49.5% fell within the 9-12 age group. The PAL group had a higher percentage of patients with an asthma duration of more than 3 years (89.7% vs. 62.0%, P<0.001) and a history of pneumonia (13.4% vs. 4.0%, P=0.036) compared to the non-PAL group. Regarding laboratory tests, a higher percentage of patients in the PAL group had an elevated FeNO level (60.9% vs. 37.6%, P=0.002) and animal sensitization (50.7% vs. 30.7%, P=0.022) compared to the non-PAL group. Of the 69 patients who underwent spirometry before and after PAL development, FEV1%pred, FEV1/FVC, and MMEF%pred values gradually decreased, with a significant decline in the year preceding PAL development. Conclusions: Asthmatic children with PAL had characteristics such as relatively older age, higher BMI, longer duration of asthma, eosinophilic inflammation, and atopy. Lung function decline occurred several years before PAL development. Long-term follow-up should focus on the evolving trend of spirometry parameters.

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STUDY DESIGN: Cross-sectional study. OBJECTIVES: Suboptimal health status (SHS) is a third state between health and disease. Long-term being SHS will be detrimental to one's ability development. Previous studies have demonstrated the associations of lifestyle behaviors or work stress with SHS, but few studies have comprehensively analyzed the underlying factors and mechanisms between the three. This study aimed to investigate whether lifestyle behaviors mediated the relationship between self-perceived work stress and SHS. METHODS: A total of 4238 urban workers, who participated in a cross-sectional survey conducted from December 2018 to October 2019, were included. A general linear model was used to explore the associations between lifestyle behaviors and self-perceived work stress with SHS after adjusting for demographic variables. Structural equation modeling was performed to examine the mediation by lifestyle behaviors. RESULTS: The mean transformed scores of physical, mental, and social SHS were 70.98, 67.17, and 61.72, respectively. Unhealthy lifestyle behaviors and high self-perceived work stress positively affected SHS (P < 0.001). Self-perceived work stress imposed negative effects on physical SHS (ß = -0.228, P < 0.001), mental SHS (ß = -0.237, P < 0.001), and social SHS (ß = -0.092, P < 0.001). The indirect effects of self-perceived work stress on physical SHS (ß = -0.139, 95% CI: -0.178 to -0.106), mental SHS (ß = -0.106, 95% CI: -0.134 to -0.082), and social SHS (ß = -0.121, 95% CI: -0.154 to -0.092) were statistically significant. CONCLUSIONS: Lifestyle behaviors and self-perceived work stress were significantly associated with SHS among Chinese urban workers. The mediating effects of unhealthy lifestyle behaviors were found in the relationship between high self-perceived work stress and SHS. Future longitudinal research may verify these associations and elucidate the underlying mechanisms.

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The assembly of discrete superatomic nanoclusters into larger constructs is a significant stride towards developing a new set of artificial/pseudo-elements. Herein, we describe a novel series of 16-electron supermolecules derived from the combination of discrete 8-electron superatomic synthons containing interstitial hydrides as vertex-sharing building blocks. The symmetric (RhH)2Ag33[S2P(OPr)2]17 (1) and asymmetric PtHPtAg32[S2P(OPr)2]17 (2) are characterized by ESI-MS, SCXRD, NMR, UV-vis absorption spectra, electrochemical and computational methods. Cluster 1 represents the first group 9-doped 16-electron supermolecule, composed of two icosahedral (RhH)@Ag12 8-electron superatoms sharing a silver vertex. Cluster 2 results from the assembly of two distinct icosahedral units, Pt@Ag12, and (PtH)@Ag12. In both cases, the presence of the interstitial hydrides is unprecedented. The stability of the supermolecules is investigated, and 2 spontaneously transforms into Pt2Ag33[S2P(OPr)2]17 (3) with thermal treatment. The lability of the hydride within the icosahedral framework in solution at low-temperature was confirmed by the VT-NMR.

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OBJECTIVE: To explore the effects of Qingshen Granules (QSG) on adenine-induced renal fibrosis in mice and in uric acid (UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes, miR-330-3p and CREBBP. METHODS: A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks. An adenoassociated virus vector was injected into the tail vein, and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9, Hsp70, and TSG101 and expressions of Col-III, α-SMA, FN, and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining. In the cell experiment, NRK-49F cells were stimulated with uric acid (400 µmol/L) followed by treatment with QSG-medicated serum from SD rats, and the changes in expressions of the exosomal markers and Col-III, α-SMA, FN, and E-cad were analyzed. Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP, whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells. RESULTS: The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9, Hsp70, and TSG101, which were decreased by treatment with QSG. The expressions of Col-III, α-SMA, and FN increased and Ecad decreased in the mouse models but these changes were reversed by QSG treatment. QSG treatment obviously alleviated renal fibrosis in the mouse models. Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p, increased CREBBP levels, and reduced fibrosis in the mouse models. Dual luciferase assay confirmed CREBBP as a target of miR-330-3p, which was consistent with the results of the cell experiments. CONCLUSION: QSG inhibits renal fibrosis in mice by regulating the exosomes, reducing miR-330-3p levels, and increasing CREBBP expression.

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BACKGROUND: Homozygous deletion of methylthioadenosine phosphorylase (MTAP) occurs in ∼10%-15% of solid tumors. AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumors cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors. PATIENTS AND METHODS: In this first-in-human, multicenter, open-label, phase 1 study, patients with advanced CDKN2A-deleted and/or MTAP-deleted solid tumors received AMG 193 orally (once [QD] or twice [BID] daily) continuously in 28-day cycle. Primary objectives were safety and tolerability assessed by dose-limiting toxicities (DLTs) and determination of the maximum-tolerated dose (MTD); secondary objectives included pharmacokinetics and preliminary antitumor activity measured by RECIST v1.1. RESULTS: As of 23 May 2024, 80 patients in dose exploration received AMG 193 at doses 40-1600 mg QD or 600 mg BID. The most common treatment-related adverse events were nausea (48.8%), fatigue (31.3%), and vomiting (30.0%). DLTs were reported in eight patients at doses ≥240 mg, including nausea, vomiting, fatigue, hypersensitivity reaction, and hypokalemia. The MTD was determined to be 1200 mg QD. Mean exposure of AMG 193 increased in a dose-proportional manner from 40 mg to 1200 mg. Among the efficacy-evaluable patients treated at the active and tolerable doses of 800 mg QD, 1200 mg QD, or 600 mg BID (n=42), objective response rate (ORR) was 21.4% (95% CI: 10.3-36.8). Responses were observed across eight different tumor types, including squamous/nonsquamous non-small cell lung cancer, pancreatic adenocarcinoma, and biliary tract cancer. At doses ≥480 mg, complete intratumoral PRMT5 inhibition was confirmed in paired MTAP-deleted tumor biopsies, and molecular responses (circulating-tumor DNA [ctDNA] clearance) were observed. CONCLUSIONS: AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on ORR and ctDNA clearance.

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BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase 1 multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, ≥ 1 ARPI, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (Part A) and expansion (Part B) of BMS-986365 up to 900 mg twice daily (BID). Primary objectives were safety, tolerability, and to define maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In Part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events (TRAEs) were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A MTD was not reached and RP2D selection is ongoing. Across Part B three highest doses (400-900 mg BID, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% CI) was 6.3 months (5.3-12.6), including 8.3 months (3.8-16.6) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5-not evaluable) versus 5.5 months (2.7-8.3), respectively. Efficacy was observed in patients with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

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The neuropsychiatric effects of probiotics, prebiotics, and synbiotics have been gaining attention since the rise of microbial-gut-brain axis research. Nevertheless, some of the findings are inconsistent, and few studies have analysed the similarities and differences in the neuropsychiatric effects of the three comprehensively. To reveal the respective neuropsychiatric effects of probiotics, prebiotics, and synbiotics and synthesise the similarities and differences among the three effects, 47 meta-analyses with 12 types of neuropsychiatric results were integrated under an umbrella review. Probiotics, prebiotics, and synbiotics intake might all be associated with improvements in some neuropsychiatric outcomes, including neuropsychological test outcomes (probiotic and prebiotic), hepatic encephalopathy outcomes (probiotic, prebiotic, and synbiotic), instant memory in patients with Alzheimer's disease (probiotic), depressive symptoms (probiotic, prebiotic and synbiotic), mood states and psychiatric distress (probiotic), overall mental health (probiotic), neurological function (probiotic), brain-derived neurotrophic factor (BDNF) concentration (probiotic and synbiotic), and Pittsburgh Sleep Quality Index (PSQI) score (probiotic). All three are similar in that the intake of probiotics, prebiotics, and synbiotics might be associated with improvements in hepatic encephalopathy outcomes and depressive symptoms, both probiotic and synbiotic intake might be associated with elevated BDNF concentrations, and both probiotic and prebiotic intake might be associated with improved neuropsychological test results. The difference between the three is that the neuropsychiatric effects of probiotics might be more widespread and be reflected in the fact that probiotic intake might also be associated with improvements in mood states and psychiatric distress, overall mental health, neurological function, Alzheimer's disease patients' instant memory, and PSQI score. Probiotics might be the best and most promising option for improving neuropsychiatric outcomes. In the future, in addition to requiring more high-quality meta-analyses, further preclinical studies are needed to explore specific relevant mechanisms and determine true causal relationships.

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Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

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OBJECTIVE: A metabolism score for visceral fat (METS-VF) is an innovative method to access abdominal fat and visceral fat. So far, the relationship between the METS-VF index and chronic obstructive pulmonary disease (COPD) has remained unclear. We investigated the relationship between the METS-VF index and COPD prevalence utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. PATIENTS AND METHODS: A binary logistic regression analysis was performed using NHANES 2007-2018 data to assess the relationship between the METS-VF index and COPD prevalence. The relationship was verified by fitted smooth curves, generalized additive models, threshold effect analyses, subgroup analyses, and sensitivity analyses. RESULTS: In total, 7,680 subjects were recruited for the study, including 772 self-reported having COPD. The METS-VF index was positively related to COPD prevalence when adjusted for all covariates. The METS-VF index was classified by quartiles, and participants who scored highest on METS-VF were at a greater risk of COPD than those who scored lowest. According to a threshold effect analysis, the METS-VF index was negatively correlated with COPD prevalence with a METS-VF index <7.00, without statistical significance. Once the METS-VF index exceeded 7.00, there was a robust positive correlation between the METS-VF index and COPD prevalence. In the analysis of subgroups, the METS-VF index was positively correlated with COPD prevalence among subjects who were male, aged 40-59, and without asthma or hypertension. The results were robust in sensitivity analyses. METS-VF showed a significantly better diagnostic value for COPD than Body Mass Index (BMI). CONCLUSIONS: The METS-VF index has a non-linear and positive correlation with COPD prevalence in the middle-aged and elderly American population.

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Objective: To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome. Methods: This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children's Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19+B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results: There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20)vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation (OR=0.26, 95%CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95%CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×106/L. Conclusions: The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×106/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.

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Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

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Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

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Objective: To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the Numerical rating scale (NRS) at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively. Results: A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] (Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference (Z=-0.78, P=0.439). Conclusions: Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

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Proliferative verrucous leukoplakia (PVL) is a special oral leukoplakia, which has the characteristics of high recurrence and canceration rate. In 2021, the American Society of Oral and Maxillofacial Pathology and the North American Association of head and neck Pathologists published "Proliferative verrucous leukoplakia: an expert consensus guideline for standardized assessment and reporting", and divided PVL into four categories: ①Corrugated ortho(para)hyperkeratotic lesion, not reactive; ②Bulky hyperkeratotic epithelial proliferation, not reactive; ③Squamous cell carcinoma, or suspicious for squamous cell carcinoma; and ④Does not fit any above category. This paper intends to interpret the new classifications of PVL in the guidelines in order to provide guidance for clinical diagnosis and treatment.

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The current version of Jing Xiao Chan Bao is believed to be the earliest medical book on gynecology remaining in China. It has three problems: formulae missing, lack of fluency in the text, and thus difficulties in proofreading and editing. These problems are still there because there are very few versions of Jing Xiao Chan Bao left in China and so it is difficult to do further studies to make comparisons. The Waseda University Library announced that the version they held was a handwritten. It provides a new version for further research of this book. This version was believed to be compiled and edited by Japanese scholars based on Medical Prescription Analogues (Yi Fang Lei Ju) and therefore appears to be similar to the South Song Dynasty version. Using archival research, it was found that in the version at Waseda University Library, the content organisation, the number of formulas, and the use of taboo words is different from those in the current version in China. In this sense, it is believed that this version is valuable and meaningful for archival and clinical research for traditional Chinese medicine.

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1. This trial investigated the effect on embryo injected with ochratoxin A (OTA) and the growth performance, jejunal morphology and barrier of ducklings to 21 d old.2. Two hundred forty, fertilised eggs were individually weighed and randomly assigned to two groups, a control (CON) and the OTA treatment, according to average egg weight. On d 13 of embryonic development, the treatment group was injected with 8 ng OTA/g egg and the CON group was injected with NaHCO3 solution as a placebo. All newly hatched ducklings were assigned to the CON or OTA group based on the different treatments. Each treatment consisted of six replicates and each included 10 ducklings and the experiment lasted until 21 d of age.3. The results showed that embryos injected with OTA affected the 21 d body weight (BW) and average daily gain (ADG) of ducklings (p < 0.05). OTA exposure increased the relative weights of the liver, pancreas, gizzard, proventriculus and jejunum (p < 0.05); and decreased the relative length of the jejunum of ducklings (p < 0.05). Moreover, jejunal crypt depth increased (p < 0.05) and the villus height-to-crypt depth ratio (Vh/Cd) decreased in the OTA-injected group (p < 0.05). Compared with those in the CON group, the mRNA expression of Zonula Occludens-1; (ZO-1) (p = 0.0582) and Occludin; (p = 0.0687) in the OTA treatment group was downregulated.4. The findings demonstrated that a single low-dose injection of OTA increased body weight and daily gain in ducklings. Moreover, embryo exposure to OTA had negative effects with increased relative weight of organs and the jejunal crypt depth, decreased relative length of the intestine and mRNA expression of tight junctions (ZO-1, Occludin).

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Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P=0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

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BACKGROUND: Posterior nasal neurectomy (PNN) is a commonly employed surgical approach for the treatment of allergic rhinitis (AR). Due to its denervation effect on the nasal mucosa, PNN may potentially alter the motion and defensive capability of cilia. Previous research on the effects of neural regulation and denervation on cilia has been limited by the absence of a feasible in vivo evaluation method for assessing ciliary function. METHODOLOGY: Utilizing a new system developed by our team for visualizing and analyzing ciliary motion in vivo, we analysed ciliary beat frequency and distance in vivo and histomorphological changes in a murine PNN and AR model. Ovalbumin, histamine and neurotransmitters (acetylcholine chloride, α receptor agonist and ß receptor agonist) were applied to investigate the responsiveness and neural regulation of the nasal mucosa. RESULTS: Denervation resulting from PNN led to a reduction in nasal ciliary beat frequency (CBF) to 78% of the control, as well as diminished response towards allergens and histamine. Among neurotransmitters examined, α receptor agonists exhibited inhibitory effects on in vivo ciliary motion while acetylcholine and ß receptor agonists demonstrated stimulatory effects. PNN did not affect the reactivity of in vivo cilia towards these neurotransmitters. CONCLUSIONS: PNN-induced denervation can reduce ciliary motion, potentially compromising the defensive capability of nasal mucosa. Neural regulation and the neurotransmitters involved have significant effect on ciliary motion.

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Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

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