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Objective: The present study aimed to explore the function of human bone marrow mesenchymal stem cells (hBMMSCs)-derived exosomal long noncoding RNA histocompatibility leukocyte antigen complex P5 (HCP5) in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to improve chronic periodontitis (CP). Methods: Exosomes were extracted from hBMMSCs. Alizarin red S staining was used to detect mineralised nodules. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure HCP5 and miR-24-3p expression. The mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin, osterix, runt-related transcription factor 2, bone morphogenetic protein 2, osteopontin, fibronectin, collagen 1, heme oxygenase 1 (HO1), P38, and ETS transcription factor ELK1 (ELK1) were detected using RT-qPCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the HO1 and carbon monoxide concentrations. Heme, biliverdin, and Fe2+ levels were determined using detection kits. Micro-computed tomography, hematoxylin and eosin staining, ALP staining, tartrate-resistant acid phosphatase staining, ELISA, and RT-qPCR were conducted to evaluate the effect of HCP5 on CP mice. Dual luciferase, RNA immunoprecipitation, and RNA pulldown experiments were performed to identify the interactions among HCP5, miR-24-3p, and HO1. Results: The osteogenic ability of hPDLSCs significantly increased when co-cultured with hBMMSCs or hBMMSCs exosomes. Overexpression of HCP5 and HO1 in hBMMSCs exosomes promoted the osteogenic differentiation of hPDLSCs, and knockdown of HCP5 repressed the osteogenic differentiation of hPDLSCs. HCP5 knockdown enhanced the inflammatory response and repressed osteogenesis in CP mice. MiR-24-3p overexpression diminished the stimulatory effect of HCP5 on the osteogenic ability of hPDLSCs. Mechanistically, HCP5 acted as a sponge for miR-24-3p and regulated HO1 expression, and HO1 activated the P38/ELK1 pathway. Conclusion: HBMMSCs-derived exosomal HCP5 promotes the osteogenic differentiation of hPDLSCs and alleviates CP by regulating the miR-24-3p/HO1/P38/ELK1 signalling pathway.

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Satellite-based formaldehyde（HCHO）columns and tropospheric nitrogen dioxide columns were observed using the Ozone Monitoring Instrument（OMI），and groundbased observations of ozone（O3）for May-August from 2013 to 2022 were connected to calculate the threshold values of the HCHO to NO2 ratio（FNR）in Shanxi Province. Then，the spatiotemporal distributions and variations in summertime ozone photochemical production regimes were analyzed. The results showed that：① The volatile organic compound（VOC） -sensitive regime area（FNR < 2.3）was obviously reduced，while the VOCs-NOx transitional regime（FNR between 2.3-4.1）area increased in the early years and then decreased， and NO x -sensitive regime area expanded significantly in summer from 2013 to 2022 over Shanxi Province. ② The increased summertime FNR during 2013 to 2019 was associated with the co-effect of increased HCHO columns and decreased tropospheric NO2 columns. The Shanxi Province was generally under an NOx regime since 2016，which reflected the remarkable effect of NO x emission reductions；however，there was a shift from a VOC-sensitive regime to a VOCs-NOx transitional regime，in which O3 pollution aggravation was widespread under the background of decreased NOx emissions. The decrease in O3 concentration during 2020 to 2022 followed the synergistical declines in HCHO columns and tropospheric NO2 columns. ③ The O3 weekend effects were reversed in Linfen and Yuncheng but were persistent in the other nine cities. Satellite-based weekend HCHO and NO2 levels were higher than those on weekdays in some cities of Shanxi Province，indicating that the O3 weekend effect was not only dependent on the changes of precursors emissions but was also closely related to O3 photochemical production sensitivity. The results indicated the necessity of simultaneous controls in NOx emissions and VOCs emissions for ozone abatement plans over Shanxi Province. In addition，Taiyuan，Yangquan，Yuncheng，and Jincheng should continue to promote reduction in NOx emissions.

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BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

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Camelina (Camelina sativa L.), a hexaploid member of the Brassicaceae family, is an emerging oilseed crop being developed to meet the increasing demand for plant oils as biofuel feedstocks. In other Brassicas, high oil content can be associated with a yellow seed phenotype, which is unknown for camelina. We sought to create yellow seed camelina using CRISPR/Cas9 technology to disrupt its Transparent Testa 8 (TT8) transcription factor genes and to evaluate the resulting seed phenotype. We identified three TT8 genes, one in each of the three camelina subgenomes, and obtained independent CsTT8 lines containing frameshift edits. Disruption of TT8 caused seed coat colour to change from brown to yellow reflecting their reduced flavonoid accumulation of up to 44%, and the loss of a well-organized seed coat mucilage layer. Transcriptomic analysis of CsTT8-edited seeds revealed significantly increased expression of the lipid-related transcription factors LEC1, LEC2, FUS3, and WRI1 and their downstream fatty acid synthesis-related targets. These changes caused metabolic remodelling with increased fatty acid synthesis rates and corresponding increases in total fatty acid (TFA) accumulation from 32.4% to as high as 38.0% of seed weight, and TAG yield by more than 21% without significant changes in starch or protein levels compared to parental line. These data highlight the effectiveness of CRISPR in creating novel enhanced-oil germplasm in camelina. The resulting lines may directly contribute to future net-zero carbon energy production or be combined with other traits to produce desired lipid-derived bioproducts at high yields.

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The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

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Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

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Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

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Triacylglycerols (TAG), accumulate within lipid droplets (LD), predominantly surrounded by OLEOSINs (OLE), that protect TAG from hydrolysis. We tested the hypothesis that identifying and removing degradation signals from OLE would promote its abundance, preventing TAG degradation and enhancing TAG accumulation. We tested whether mutating potential ubiquitin-conjugation sites in a previously reported improved Sesamum indicum OLE (SiO) variant, o3-3 Cys-OLE (SiCO herein), would stabilize it and increase its lipogenic potential. SiCOv1 was created by replacing all five lysines in SiCO with arginines. Separately, six cysteine residues within SiCO were deleted to create SiCOv2. SiCOv1 and SiCOv2 mutations were combined to create SiCOv3. Transient expression of SiCOv3 in Nicotiana benthamiana increased TAG by two-fold relative to SiCO. Constitutive expression of SiCOv3 or SiCOv5, containing the five predominant TAG-increasing mutations from SiCOv3, in Arabidopsis along with mouse DGAT2 (mD) increased TAG accumulation by 54% in leaves and 13% in seeds compared with control lines coexpressing SiCO and mD. Lipid synthesis rates increased, consistent with an increase in lipid sink strength that sequesters newly synthesized TAG, thereby relieving the constitutive BADC-dependent inhibition of ACCase reported for WT Arabidopsis. These OLE variants represent novel factors for potentially increasing TAG accumulation in a variety of oil crops.

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BACKGROUND: The increasing prevalence of multimorbidity has created a serious global public health problem in aging populations. Certain multimorbidity patterns across different age ranges and their association with health status remain unclear. The main aim of this study is to identify multimorbidity patterns discrepancies and associated health status between younger-old and oldest-old. METHODS: The Ethics Committee of Nanjing Medical University approved the study protocol (No.2019-473). Convenience sampling method was used to recruit older adults aged ≥ 60 years with multimorbidity from July to December 2021 from 38 Landsea long-term care facilities in China. The multimorbidity patterns were analyzed using network analysis and two-step cluster analysis. One-Way ANOVA was utilized to explore their association with health status including body function, activity of daily living, and social participation. A Sankey diagram visualized the flow of health status within different multimorbidity patterns. This study is reported following the STROBE guidelines. RESULTS: A total of 214 younger-old (60-84 years) and 173 oldest-old (≥ 85 years) were included. Leading coexisting diseases were cardiovascular disease (CD), metabolic and endocrine disease (MED), neurological disease (ND), and orthopedic disease (OD). Cluster 1 (53, 24.8%) of CD-ND (50, 94.3%; 31, 58.8%), cluster 2 (39, 18.2%) of MED-ND-CD (39, 100%; 39, 100%; 37, 94.9%), cluster 3 (37, 17.3%) of OD-CD-MED-ND (37, 100%; 33, 89.2%; 27, 73.0%; 16, 43.2%), and cluster 4 (34, 15.9%) of CD-MED (34, 100%; 34, 100%) were identified in the younger-old. In the oldest-old, the primary multimorbidity patterns were: cluster 1 (33, 19.1%) of CD-respiratory disease-digestive disease-urogenital disease (CD-RD-DSD-UD) (32, 97.0%; 9, 27.3%; 8, 24.2%; 7, 21.2%), cluster 2 (42, 24.3%) of ND-CD-MED (42, 100%; 35, 83.3%; 14, 33.3%), cluster 3 (28, 16.2%) of OD-CD-MED (28, 100%; 25, 89.3%; 18, 64.3%), and cluster 4 (35, 20.2%) of CD-MED (35, 100%; 35, 100%). Younger-old with CD-ND or MED-ND-CD, and oldest-old with ND-CD-MED have worse health status compared with other multimorbidity patterns (e.g., CD-MED and OD-CD-MED). CONCLUSION: Discrepancies in common patterns of multimorbidity across age groups suggest that caregivers in long-term care facilities should consider changes in multimorbidity patterns with ageing when developing prevention plans for individualized management. Neurological disease concurrent with other diseases was the major determinant of health status, especially for the oldest-old. Interventions targeting multimorbidity need to be focused, yet generic. It is essential to assess complex needs and health outcomes that arise from different multimorbidity patterns and manage them through an interdisciplinary approach and consider their priorities to gain high-quality primary care for older adults living in long-term care facilities.

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BACKGROUND: Chronic prostatitis (CP) is a common condition that affects many individuals. Previous clinical trials have explored the use of moxibustion as a potential treatment for CP. However, the evidence on the effectiveness of moxibustion for CP remains limited. Therefore, this study aimed to comprehensively assess the effects of moxibustion for CP. METHODS: In order to gather relevant and up-to-date information, we conducted a systematic literature search of databases including Cochrane Library, PUBMED, EMBASE, CNKI, and Wangfang from inception until June 30, 2023. Only randomized clinical trials (RCTs) that investigated the use of moxibustion for CP were included in this study. The primary outcomes of interest were the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores and the overall response rate. To evaluate the quality of the included studies, we used the Cochrane risk-of-bias tool. RESULTS: After analyzing the data from 8 RCTs involving a total of 664 patients, we found significant differences in NIH-CPSI scores between moxibustion and other treatment modalities. Specifically, when compared with herbal medicine, moxibustion was associated with a mean difference (MD) of -1.78 in NIH-CPSI scores (95% confidence interval [CI] [-2.78, -0.78], P < .001), and when compared with western medicine, moxibustion was associated with a MD of -5.24 in NIH-CPSI scores (95% CI [-7.80, -2.67], P < .08). In terms of the overall response rate, moxibustion was found to be superior to herbal medicine, with a MD of 2.36 (95% [19, 4.67], P = .01). Additionally, when moxibustion was combined with herbal medicine, it yielded a higher overall response rate with a MD of 4.07 (95% CI [1.54, 10.74], P = .005) compared to herbal medicine alone. Moxibustion also outperformed western medicine in terms of the overall response rate, with a MD of 4.56 (95% CI [2.24, 9.26], P < .001). CONCLUSION: Based on the findings of this study, moxibustion appears to be a potentially efficacious treatment for CP. The results suggest that moxibustion can improve NIH-CPSI scores and overall response rate in patients with CP. However, further high-quality studies are needed to validate these results and establish the long-term effects of moxibustion as a treatment for CP.

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OBJECTS: Dementia has physical, social and economic impacts, causing considerable distress for people with age-related cognitive impairment (PWACI) and their caregivers. Electronic health (e-health) interventions can provide convenient education to improve the coping competence of caregivers and have become an important approach to supporting them. Understanding the economic evidence of e-health interventions will facilitate the decision making and implementation of integrating e-health into routine health services. The present review aimed to appraise economic evidence related to e-health interventions for PWACI and their caregivers. METHODS: We systematically searched multiple cross-disciplinary databases from inception to February 28, 2023. Two reviewers independently selected the trials, assessed the quality, and checked the data. A descriptive-analytical narrative method was used to analyze the review findings. RESULTS: Thirteen studies were analyzed, including 12 randomized controlled trials and one quasi-experimental study. All included studies were conducted in developed countries. The included studies reported limited economic information. There were six cost-effectiveness analysis, five cost-consequence analysis and one partial economic evaluation. The included studies were heterogeneous, and varied in quality. The results demonstrated that e-health multicomponent interventions can reduce the cost of health service utilization in short term (10-104 weeks). CONCLUSIONS: Few studies calculated the incremental cost-effectiveness ratio to evaluate the cost-effectiveness of e-health interventions. Preliminary evidence indicates that e-health interventions can reduce the cost of health service utilization in the short term, but the cost-effectiveness of e-health interventions hasn't been identified. More robust evidence is needed to clarify the value of e-health interventions for PWACI and their caregivers.

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OBJECTIVE: To explore risk factors for infections after arthroscopic rotator cuff repair, and improve the under standing for reducing infection. METHODS: Clinical data of 2 591 patients who underwent arthroscopic rotator cuff repair from January 2019 to January 2022 were retrospectively analyzed, including 1 265 males and 1 326 females, aged from 25 to 82 years old with an average age of (51.5±15.6) years old. They were divided into infection group(n=18) and uninfected group(n=2 573) according to whether or not patients had postoperative infection. Gender, age, smoking, diabetes, body mass index, local closure within 1 month before operation, operation time, preventive use of antibiotics, and internal fixation implantation between two groups were recorded. Univariate Logistic regression analysis screened factors associated with infections after arthroscopic rotator cuff repair. Theresultswere entered into the multivariate logistic regression analysis, screening the high risk factors for infections after arthroscopic rotator cuff repair. RESULTS: In 2 591 patients, 18 patients were infected after operation, infection rate was 0.69%. Univariate Logistic regression analysis showed that gender, age, operation time, antibiotic prophylaxis, internal fixation implantation were risk factors for infections after arthroscopic rotator cuff repair. Multivariate Logistic regression analysis showed male(OR=14.227), age≥65 years(OR=34.313), operation time≥2 h (OR=15.616), without antibiotic prophylaxis(OR=4.891), and internal fixation implantation(OR=5.103) were major risk factors for infection after arthroscopic rotator cuff repair(P<0.05). CONCLUSION: Male, age≥65 years, operation time≥2 h, without antibiotic prophylaxis and internal fixation implantation were independent risk factors for infection after arthroscopic rotator cuff repair. Early diagnosis and timely treatment should be carried out to reduce the incidence of infection.

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BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD. PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile. METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT). RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism. CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.

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Duckweeds are amongst the fastest growing of higher plants, making them attractive high-biomass targets for biofuel feedstock production. Their fronds have high rates of fatty acid synthesis to meet the demand for new membranes, but triacylglycerols (TAG) only accumulate to very low levels. Here we report on the engineering of Lemna japonica for the synthesis and accumulation of TAG in its fronds. This was achieved by expression of an estradiol-inducible cyan fluorescent protein-Arabidopsis WRINKLED1 fusion protein (CFP-AtWRI1), strong constitutive expression of a mouse diacylglycerol:acyl-CoA acyltransferase2 (MmDGAT), and a sesame oleosin variant (SiOLE(*)). Individual expression of each gene increased TAG accumulation by 1- to 7-fold relative to controls, while expression of pairs of these genes increased TAG by 7- to 45-fold. In uninduced transgenics containing all three genes, TAG accumulation increased by 45-fold to 3.6% of dry weight (DW) without severely impacting growth, and by 108-fold to 8.7% of DW after incubation on medium containing 100 µm estradiol for 4 days. TAG accumulation was accompanied by an increase in total fatty acids of up to three-fold to approximately 15% of DW. Lipid droplets from fronds of all transgenic lines were visible by confocal microscopy of BODIPY-stained fronds. At a conservative 12 tonnes (dry matter) per acre and 10% (DW) TAG, duckweed could produce 350 gallons of oil/acre/year, approximately seven-fold the yield of soybean, and similar to that of oil palm. These findings provide the foundation for optimizing TAG accumulation in duckweed and present a new opportunity for producing biofuels and lipidic bioproducts.

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RATIONALE: Cancer with unknown primary site is a kind of disease that is difficult to deal with clinically, accounting for 2% to 9% of all newly diagnosed cancer cases. Here, we report such a case with pelvic metastatic squamous cell carcinoma of an unknown primary site and review the relevant literature. PATIENT CONCERNS DIAGNOSES: A 43-year-old Chinese female patient was referred to our hospital and initially diagnosed as "malignant tumor of right adnexal area?, obstruction of right ureter, secondary hydronephrosis". INTERVENTIONS: Thereafter cytoreductive surgery was performed which included a total hysterectomy, left adnexectomy, partial omentum resection, pelvic lymph node dissection, and para-aortic lymph node dissection. The primary lesion could not be identified by supplementary examination and postoperative pathology. The patient was diagnosed as pelvic metastatic squamous cell carcinoma whose primary site was unknown. To prevent a recurrence, we administered adjuvant chemotherapy for the patient. OUTCOMES: The patient was followed up after treatment, complete remission has been maintained for 72 months, and no recurrence or metastasis has been found. LESSONS: Our case demonstrates that surgery combined with chemotherapy could be helpful for pelvic metastatic squamous cell carcinoma of unknown primary site.

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Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-ß/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF.

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Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix-loop-helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and molecular mechanism in AF remain unclear. In this study, a mouse model of AF was induced by Ang II infusion. The atrial diameter was evaluated using echocardiography. Induction and duration of AF were measured by programmed electrical stimulation. Atrial structural remodeling was detected using routine histologic examinations. Our results showed that Bhlhe40 was significantly upregulated in angiotensin II (Ang II)-stimulated atrial cardiomyocytes and atrial tissues and in tissues from patients with AF. Cardiac-specific knockdown of Bhlhe40 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shBhlhe40 significantly ameliorated Ang II-induced atrial dilatation, atrial fibrosis, and atrial inflammation, as well as the inducibility and duration of AF. Mechanistically, cardiac-specific knockdown of Bhlhe40 attenuated Ang II-induced activation of NF-κB/NLRP3, TGF-1ß/Smad2 signals, the increased expression of CX43, and the decreased expression of Kv4.3 in the atria. This is the first study to suggest that Bhlhe40 is a novel regulator of AF progression, and identifying Bhlhe40 may be a new therapeutic target for hypertrophic remodeling and heart failure.

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BACKGROUND: This study assessed the effectiveness of Yangxin Decoction (YXD) in the treatment of coronary heart disease (CHD) patients with angina pectoris (AP). METHODS: In this study, we systematically and comprehensively searched the PUBMED, EMBASE, Cochrane Library, CNKI, WANGFANG, and VIP databases from their establishment to June 1, 2022. Clinical randomized controlled trials of YXD for the management of AP in patients with CHD were considered for inclusion. The outcomes included the response rate of AP, response rate based on electrocardiogram, and the rate of nitroglycerin use. Two authors independently performed literature selection, data extraction, and methodological quality assessment. Any differences were resolved by a third author through a discussion. RESULTS: Nine trials involving 819 patients were included. The meta-analysis results showed that YXD significantly improved the response rate of AP (OR = 2.98, 95% CI: 1.96-4.55, I2 = 0%, P < .01) and the response rate based on the electrocardiogram (OR = 1.88, 95% CI: 1.28-2.78, I2 = 26%, P < .01), and significantly reduced the rate of nitroglycerin use (OR = 2.04, 95% CI: 1.19-3.52, I2 = 0%, P = .01). CONCLUSIONS: The results of this study showed that YXD was effective in the treatment of patients with AP of CHD. Further studies are required to confirm these results.

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BACKGROUND: In recent years, the cosmetic intervention related infections caused by nontuberculous mycobacteria (NTM) are increasing as the informal cosmetic treatments are performed. However, many dermatologists are inexperienced in the diagnosis and management of similar cases. Here we report a case of subcutaneous infection caused by Mycobacterium abscessus (M. abscessus) following cosmetic injections of botulinum toxin. CASE SUMMARY: A 53-year-old woman presented with multiple abscesses and nodules on her forehead and both temporal sites for half a month after cosmetic injections of botulinum toxin. Her lesions did not show any alleviation after 2-wk prescription of antibiotics. Laboratory examinations indicated that she had no sign of immunodeficiency and the whole body of computed tomography did not find any systemic infection or diseases. The pathology of skin tissue showed inflammatory cell infiltration with the negative results of Periodic acid Schiff (PAS) and Acid-fast staining and the culture yielded no microbiome. Afterwards, the puncture on abscess was performed and M. abscessus was successfully isolated. The pathogen was identified by acid-fast staining and DNA sequencing. The patient was treated with the strategy of clarithromycin, ofloxacin, and amikacin according to the result of drug sensitivity test and got complete remission of the lesions. CONCLUSION: The case presents the whole process of diagnosis and management of NTM infection after cosmetic intervention and highlights the diagnostic thoughts. In a word, the mycobacterium infection should be aware in patients after cosmetic performance.