[The effect of ubiquitin ligase Cullin3 on the proliferation, migration and invasion of triple-negative breast cancer cells and exploration of its mechanism].

Objective: To investigate the effects of ubiquitin ligase Cullin3 (CUL3) on the proliferation, migration and invasion ability of triple-negative breast cancer (TNBC) cells and its mechanism of action. Methods: Bioinformatics-based methods were used to obtain CUL3 gene and protein expression data in TNBC tissues, and to assess the expression of CUL3 in tumour tissues of TNBC patients (n=160) and in normal breast tissues (n=572), and its relationship with clinical prognosis. The effects of overexpression of CUL3 on the proliferation, migration and invasion ability of TNBC cells in vitro were detected by CCK8 cell proliferation assay, scratch assay and transwell assay; proteins that might interact with CUL3 were screened by immunoprecipitation combined with mass spectrometry analysis, and the substrate protein regulated by CUL3 was identified as Glutathione S-Transferase Pi 1 (GSTP1); the effects of overexpression of GSTP1 on the migration and invasion ability of TNBC cells were detected by scratch assay and Transwell assay, and it was explored whether overexpression of CUL3 could reverse the effects of GSTP1 on the migration and invasion ability of cells; and the effects of overexpression of GSTP1 on the migration and invasion ability of cells were detected by Western blot and IP (Immunoprecipitation) to detect the effect of CUL3 on the ubiquitination modification of GSTP1 protein, and to verify the molecular mechanism by which CUL3 regulates the expression of GSTP1 to affect TNBC migration and invasion. Results: CUL3 expression was significantly higher in TNBC (P<0.000 1), and high CUL3 expression was closely associated with poor prognosis of TNBC patients (OS, P=0.018; RFS, P=0.008); overexpression of CUL3 significantly increased the proliferation of TNBC cells (F=11.97, P=0.002 for the 231-cell group, F=51.92, P<0.001 for the 468-cell group), migration [74.7±4.0 and 128.0±6.1 perforating cells in the overexpression groups of 231 and 468 cell lines, compared with 21.0±2.7 and 70.0±6.6 in the blank control (NC) group, and the t-values of 231 and 468 cell groups were-19.24 and-11.23, with P-values<0.001] and invasive ability (48 h cell proliferation rates were 56.6%±4.4% and 51.6%±3.7% in the 231 and 468 cell line overexpression groups, compared with 40.5%±2.9% and 32.9%±4.8% in the NC group, respectively, t=-5.26, P=0.006 3 in the 231 cell group; t=-5.38 in the 468 cell group, P=0.005 8); GSTP1 expression was reduced in TNBC, and up-regulation of GSTP1 inhibited TNBC cell migration (the number of membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines were 16.3±6.5 and 33.0±6.2, respectively, compared with 34.3±2.5 and 77.3±5.0 in the NC group, and t=5.44 in the 231 cell group, P=0.006; 468 cell group t=7.20, P=0.002) and invasion (48 h cell proliferation rates of 49.6%±1.7% and 36.2%±1.4% in the 231 and 468 cell line overexpression groups, compared to 59.4%±4.7% and 53.0%±1.7% in the NC group, t=3.42, P=0.027 in the 231 cell group; 468 cell group t=13.18, P<0.001), whereas up-regulation of CUL3 reversed the effects of GSTP1 on cell migration (37.0±1.0 and 67.0±5.3 membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines, respectively, 231 cell group t=-3.97, P=0.017; 468 cell group t=-6.12, P=0.004), and invasion (48 h cell proliferation rates of 71.9%±3.6% and 59.4%±2.1% in the 231 and 468 cell line overexpression groups, respectively, with t-values of -9.61 and -16.01 in the 231 and 468 cell groups, respectively, P-values<0.001) inhibitory effects; and CUL3, by increasing GSTP1 ubiquitylation modification, promotes ubiquitin-proteasome system to degrade GSTP1 protein, thereby reducing the stability of GSTP1 protein. Conclusion: Overexpression of CUL3 promotes TNBC development by promoting GSTP1 ubiquitination degradation inducing cell migration and invasion.

[Etiological characterization of invasive non-typhoid Salmonella strains in Guangdong Province from 2018 to 2022].

Objective: To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods: Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results: The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions: The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022. iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.

[Regulation mechanism of the quorum sensing regulator AphA on the type â ¥ secretion system VflT6SS2 in Vibrio fluvialis].

Objective: To explore the regulation mechanism of the quorum sensing regulator AphA on the functional activity of type Ⅵ secretion system VflT6SS2 in Vibrio fluvialis. Methods: Western Blot analysis was used to detect the relative expression and secretion of VflT6SS2 signature component hemolysin-coregulated protein (Hcp) in wild type (WT), ΔaphA, and corresponding complementary strains. Quantitative reverse transcription PCR and luminescence activity assay of the promoter-lux fusion system was used to measure the mRNA expression levels and promoter activity of the VflT6SS2 core and accessory gene-cluster representative genes tssB2, hcp (tssD2) and vgrG (tssI2), and the quorum sensing regulator HapR in WT and ΔaphA strains. A point mutation experiment combined with a luminescence activity assay was used to verify the regulatory binding site of AphA in the tssD2b promoter region. Electrophoretic mobility shift assay (EMSA) was used to determine AphA binding to the hapR promoter. Results: The mRNA expression levels of tssB2, hcp(tssD2), vgrG (tssI2), and hapR as well as the protein expression and secretion levels of Hcp in ΔaphA strain, were significantly higher than those in the WT strain. The promoter activities of the VflT6SS2 core cluster, tssD2a, tssI2a, and hapR were higher in ΔaphA strain than in the WT strain, while the promoter activity of tssD2b showed the opposite trend. The promoter sequence analysis of tssD2a and tssD2b found significant differences in the region from -335 bp to -229 bp, and two potential AphA binding sites on tssD2b. The promoter activity of tssD2b decreased significantly after the point mutation of the two potential AphA binding sites. EMSA results showed that AphA binds directly to the promoter region of hapR. Conclusions: AphA indirectly inhibits the regulation of the VflT6SS2 core and accessory gene clusters at the promoter level by directly repressing the expression of hapR. AphA showed opposite regulation patterns for tssD2a and tssD2b, and AphA could positively regulate the expression of tssD2b by directly binding to the tssD2b promoter region (-335 bp to -229 bp).

Body mass index, weight change, and cancer prognosis: a meta-analysis and systematic review of 73 cohort studies.

BACKGROUND: Identifying the association between body mass index (BMI) or weight change and cancer prognosis is essential for the development of effective cancer treatments. We aimed to assess the strength and validity of the evidence of the association between BMI or weight change and cancer prognosis by a systematic evaluation and meta-analysis of relevant cohort studies. METHODS: We systematically searched the PubMed, Web of Science, EconLit, Embase, Food Sciences and Technology Abstracts, PsycINFO, and Cochrane databases for literature published up to July 2023. Inclusion criteria were cohort studies with BMI or weight change as an exposure factor, cancer as a diagnostic outcome, and data type as an unadjusted hazard ratio (HR) or headcount ratio. Random- or fixed-effects models were used to calculate the pooled HR along with the 95% confidence interval (CI). RESULTS: Seventy-three cohort studies were included in the meta-analysis. Compared with normal weight, overweight or obesity was a risk factor for overall survival (OS) in patients with breast cancer (HR 1.37, 95% CI 1.22-1.53; P < 0.0001), while obesity was a protective factor for OS in patients with gastrointestinal tumors (HR 0.67, 95% CI 0.56-0.80; P < 0.0001) and lung cancer (HR 0.67, 95% CI 0.48-0.92; P = 0.01) compared with patients without obesity. Compared with normal weight, underweight was a risk factor for OS in patients with breast cancer (HR 1.15, 95% CI 0.98-1.35; P = 0.08), gastrointestinal tumors (HR 1.54, 95% CI 1.32-1.80; P < 0.0001), and lung cancer (HR 1.28, 95% CI 1.22-1.35; P < 0.0001). Compared with nonweight change, weight loss was a risk factor for OS in patients with gastrointestinal cancer. CONCLUSIONS: Based on the results of the meta-analysis, we concluded that BMI, weight change, and tumor prognosis were significantly correlated. These findings may provide a more reliable argument for the development of more effective oncology treatment protocols.

Two-Stage Treatment Protocol of Fungal Periprosthetic Hip and Knee Joint Infections: the Clinical Experience from a Single Center Experience.

PURPOSE OF THE STUDY: To evaluate the clinical results and safety of fungal periprosthetic joint Infections (fPJIs) using two-stage treatment protocol. MATERIAL AND METHODS: 8 patients with fPJIs (3 hips and 5 knees) using two-stage revision were reviewed retrospectively and followed up at least 2 years. The preoperative demographic data, two-stage treatment protocol, results of microbiology and histologic workup and postoperative follow-up results (reimplantation success rate and infection free time) were recorded. RESULTS: 7 patients got successful reimplantation, with a 75% reimplantation success rate. Two patients got knee arthrodesis eventually. All patients were infection free with a median follow-up of 4.0 ± 2.0 years (range, 2-7 years). Of them, Candida species were found in 7 patients, while non-Candida specimen was only isolated in 1 patient with Aspergillus. Only 2 patients had coexisting bacterial infection (Methicillin-resistant coagulase-negative Staphylococci and Proteus mirabilis respectively). The average interval between the initial surgery and diagnosis of fPJIs was 21.50±34.79 months (range, 4-104 months). The mean time of spacer implantation was 7.75±2.77 months (range, 6-14 months). None serious complication or above knee amputation was found. DISCUSSION: fPJIs are very rare and considerable challenge after total hip or knee arthroplasty. The goal of therapy is to eradicate local infection and maintain function. Candida species were the most common pathogen. The duration between spacer placement and staged reimplantation was highly variable, and generally dependent upon the results of joint aspirates and infl ammatory markers. The current study shows that the two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. CONCLUSIONS: The two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. The safety and effi cacy of biantibiotical impregnated (antifungal + antibiotics) cement spacer is confi rmed. Further evidence-based work is needed to determine the optimal drug dose and reimplantation time. KEY WORDS: two-stage treatment protocol, fungal periprosthetic infections, hip spacer, knee spacer.

[Cryotherapy combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis: a case report].

Nasopharyngeal tuberculosis refers to the tuberculosis in the nasopharynx, which is mainly treated with systemic chemotherapy with anti-tuberculosis drugs. Here, we reported a case of nasopharyngeal tuberculosis treated by cryosurgery combined with local spraying of isoniazid on the basis of systemic chemotherapy with anti-tuberculosis drugs. By reviewing the case data and relevant literature, we understood the clinical manifestations, diagnosis and differential diagnosis of the disease, improved everyone's understanding of the disease, and proposed a new method of cryosurgery combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis for clinical discussion.

[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. 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 were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

[Well-differentiated/dedifferentiated liposarcoma associated with myxoid-like morphology: a clinicopathological and molecular genetic characteristics analysis of 34 cases].

Objective: To investigate the clinicopathological and molecular genetic characteristics of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) with myxoid-like morphology, and to distinguish them from myxofibrosarcoma (MFS) with similar morphology. Methods: Twenty-nine cases of myxoid-like liposarcoma and 5 cases of MFS were collected from Henan Provincial People's Hospital, Zhengzhou, China and the First Medical Center of PLA General Hospital, Beijing, China from January 2015 to March 2023. Relevant markers were detected using immunohistochemistry and fluorescence in situ hybridization (FISH). The literature was also reviewed. Results: There were 24 males and 10 females, with ages ranging from 41 to 73 years. The tumor sites included retroperitoneum (n=17), abdomen (n=9), lower limbs (n=5), scrotum (n=1), upper limb (n=1) and axilla (n=1). WDLPS was commonly seen as lipomatoid type (12 cases), while the dedifferentiated components of DDLPS included low-grade (13 cases) and high-grade (2 cases) morphology, with low-high grade myxofibrosarcoma, dermatofibrosarcoma protuberans, and low-grade fibrosarcoma structures. Twenty-nine liposarcomas had various proportions of myxoid-like morphology, while 16 showed various degrees of tumor necrosis. The myxoid-like component showed myxoid pleomorphic liposarcoma (MLPS)-like morphology, lobulated growth, characteristic slender, ramified capillary network,"chicken claw-like"morphology, mucus-rich stroma and lung edema-like morphology. Tumor cells were spindle and oval, with many variable vacuolar lipoblasts. MDM2 gene amplification was detected using FISH and present in all tested cases (29/29). DDIT3 break-apart mutation was not detected, but its cluster amplification was present (24/29). Among the MFS cases, one showed cluster amplification (1/5), but no cases showed break-apart or amplification of MDM2 gene. Conclusions: WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.

[Primary synovial sarcoma of lung: a clinicopathological analysis of 12 cases].

Objective: To investigate the clinicopathological features, immunophenotype, molecular features and differential diagnosis of primary synovial sarcoma of the lung (PSSL). Methods: Twelve cases of PSSL were collected at Henan Provincial People's Hospital, during May 2010 and April 2021, and their clinicopathological parameters were summarized. SS18-SSX, H3K27Me3, and SOX2 were added to the original immunomarkers to evaluate their diagnostic value for PSSL. Results: The age of 12 patients when diagnosed ranged from 32 to 75 years (mean of 50 years). There were 7 males and 5 females, 2 left lung cases and 10 right lung cases. Of the 6 patients who underwent surgical resection, five cases were confined to lung tissue (T1), one case had mediastinal invasion (T3), two cases had regional lymph node metastasis (N1), and none had distal metastasis. Microscopically, 11 cases showed monophasic spindle cell type and one case showed biphasic type composed of mainly epithelial cells consisting of cuboidal to columnar cells with glandular and cribriform structures. It was difficult to make the diagnosis by using the biopsy specimens. Immunohistochemistry (IHC) showed CKpan expression in 8 of 12 cases; EMA expression in 11 of 12 case; TLE1 expression in 8 of 12 cases; S-100 protein expression in two of 12 cases; various expression of bcl-2 and vimentin in 12 cases, but no expression of SOX10 and CD34 in all the cases. The Ki-67 index was 15%-30%. The expression of SS18-SSX fusion antibody was diffusely and strongly positive in all 12 cases. SOX2 was partially or diffusely expressed in 8 of 12 cases, with strong expression in the epithelial component. H3K27Me3 was absent in 3 of 12 cases. SS18 gene translocation was confirmed by fluorescence in situ hybridization (FISH) test in all 12 samples. Six cases underwent surgery and postoperative chemotherapy, while the other six cases had chemotherapy alone. Ten patients were followed up after 9-114 months, with an average of 41 months and a median of 26 months. Five patients survived and five died of the disease within two years. Conclusions: PSSL is rare and has a broad morphological spectrum. IHC and molecular tests are needed for definitive diagnosis. Compared with current commonly used IHC markers, SS18-SSX fusion antibody has better sensitivity to PSSL, which could be used as an alternative for FISH, reverse transcription-polymerase chain reaction or next generation sequencing in the diagnosis of PSSL.

Global burden of neoplasms attributable to specific occupational carcinogens over 30 years: a population-based study.

OBJECTIVES: The study aimed to analyze the global burden of occupational neoplasms from various epidemiological perspectives. STUDY DESIGN: In this cross-sectional study, secondary analyses were conducted to assess the burden of neoplasms attributable to occupational carcinogens and their distribution characteristics using data from GBD 2019 and the World Bank database. METHODS: Based on the GBD 2019 and the World Bank database, we analyzed the global burden of occupational neoplasms including the age-period-cohort model, decomposition analysis, health inequality analysis, and panel model. All analyses were conducted in R (version 4.0.3) and Joinpoint (version 4.9.1). RESULTS: The absolute number of neoplasms burden attributable to occupational carcinogens has continued to rise over 30 years. In 2019, occupational neoplasms caused 333,867 [95% uncertainty interval (UI): 263,491 to 404,641] mortalities and 6,964,775 (95% UI: 5,467,884 to 8,580,431) disability-adjusted life years (DALYs) globally. Greenland, Monaco, the Netherlands, and Andorra suffered the highest burden. The burden was higher in countries with a higher sociodemographic index. The age effect was prominent in the elderly, and the 1925 birth cohort had the highest cohort effect. Population growth was the most significant driver of the mortalities (89%) and DALYs (111%) change. Moreover, the proportion of urban population was significantly positively associated with the disease burden, while GDP per capita was negatively correlated with the disease burden. CONCLUSIONS: The burden of occupational neoplasms was unevenly distributed across locations and populations. The need for rational allocation of healthcare resources was urgent.

[Bronchial tuberculosis complicated with massive hemorrhage after Dieulafoy's disease biopsy: a case report].

Compared with simple bronchial Dieulafoy's disease, bronchial tuberculosis with Dieulafoy's disease is rarer and more complex, with non-specific clinical manifestations. In this article, we reported a case of right lateral basal segment bronchial tuberculosis complicated with Dieulafoy's disease. The clinical manifestations, microscopic features, and rescue procedures in the event of massive hemorrhage in this case were described in detail, and the shortcomings in the clinical diagnosis and treatment of this case were analyzed. The aim of this study was to improve clinicians' understanding of bronchial tuberculosis combined with Dieulafoy's disease.

A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS).

Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database. INTRODUCTION: We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively. METHODS: Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test. RESULTS: We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (n=4154), compared to 62.26% reported by consumers (n=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (n=13), waist circumference increased (n=21), sensory disturbance (n=103), tinnitus (n=65), visual acuity reduced (n=54), blood alkaline phosphatase increased (n=61), and hair growth abnormal (n=13). Patient age (p < 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0-7 days. CONCLUSION: Our study provided a deeper and broader understanding of abaloparatide's safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.

[Influencing factors of the adverse outcome of pulmonary tuberculosis among adolescents in Hangzhou City between 2005 and 2020: a school-based retrospective cohort study].

Objective: To explore the influencing factors of the adverse outcome of pulmonary tuberculosis (PTB) among adolescents in Hangzhou City between 2005 and 2020. Methods: A retrospective cohort study was used to collect the information of adolescent PTB patients with the onset of PTB occurring from January 1, 2005 to December 31 in 12 designated tuberculosis hospitals in Hangzhou, mainly including demographic, epidemiological, clinical manifestations, bacteriological characteristics and other data, through the China Management Information System for Infectious Disease Surveillance and Reporting and the follow-up survey. All patients were followed up and the end time was December 31, 2021. Multivariate Cox regression model was used to analyze the factors affecting the adverse outcome of these patients. Results: The mean age of 4 921 adolescent PTB patients was (18.9±3.6) years old, and the number of male and female patients were 3 074 and 1 847 respectively. The adverse outcome accounted for 14.7% (725) of all patients. Multivariate Cox regression model showed that eight risk factors, including management model from patients themselves or family members (HR=5.87, 95%CI: 4.55-7.64), molecular biology examination positive for PTB (HR=4.62, 95%CI: 2.98-7.19), the number of sputum smears-positive≥1 (HR=3.72, 95%CI: 2.87-4.83), non-standardized therapy regimens of PTB (HR=3.69, 95%CI: 2.95-4.64), history of retreated PTB (HR=2.22, 95%CI: 1.46-3.36), migrant adolescents (HR=1.89, 95%CI: 1.54-2.34), the number of chest X-ray scan (HR=1.83, 95%CI: 1.65-2.04), and severe PTB (HR=1.38, 95%CI: 1.02-2.05), were associated with the adverse outcome of adolescent PTB patients. Age (HR=0.94, 95%CI: 0.92-0.96), as the only protective factor, was associated with the adverse outcome of these patients. Conclusion: The management mode, molecular biological examination, chemotherapy program, history of tuberculosis, sputum smear examination, severity of tuberculosis, household residence, chest X-ray examination and age are associated with the adverse outcomes of adolescent PTB patients in Hangzhou.

Emergent Majorana zero-modes in an intrinsic anti-ferromagnetic topological superconductor Mn2B2 monolayer.

Topological superconductors (TSCs) are an exotic field due to the existence of Majorana zero-modes (MZM) in the edge states that obey non-Abelian statistics and can be used to implement topological quantum computations, especially for two-dimensional (2D) materials. Here we predict manganese diboride (Mn2B2) as an intrinsic 2D anti-ferromagnetic (AFM) TSC based on the magnetic and electronic structures of Mn and B atoms. Once Mn2B2 ML enters a superconducting state, MZM will be induced by the spin-polarized helical gapless edge states. The Z2 topological non-trivial properties are confirmed by Wannier charge centers (WCC) and the platform of the spin Hall conductivity near the Fermi level. Phonon-electron coupling (EPC) implies s-wave superconductivity and the critical temperature (Tc) is 6.79 K.

[A cross-sectional study of prevalence of chronic kidney disease and related factors in adults in Anhui province].

Objective: To understand the prevalence of chronic kidney disease (CKD) and related factors in adults in Anhui province based on the data of Chinese Chronic Diseases and Nutrition Surveillance program (2018) in Anhui. Methods: Multi-stage stratified cluster random sampling was used to select participants aged ≥18 years. Moreover, questionnaire survey, body measurements and laboratory tests were conducted. The complex weighting method was used to estimate the prevalence of CKD in residents with different characteristics, and complex sampling data logistic regression model was used for multivariate analysis to identify related risk factors. Results: A total of 7 181 participants were included. The overall prevalence of CKD was 11.06% in adults in Anhui, and the prevalence was 12.49% in women and 9.59% in men (P<0.05). The moderate, high and very high risk for CKD progression were 8.66%, 2.02% and 0.38%, respectively. Multivariate analysis showed that age (OR=1.03, 95%CI: 1.00-1.05), BMI (OR=1.05, 95%CI: 1.01-1.09), being woman (OR=1.38,95%CI: 1.22-1.55), hypertension (OR=2.50, 95%CI: 1.76-3.56), diabetes (OR=2.28, 95%CI: 1.51-3.43), dyslipidemia (OR=1.26, 95%CI: 1.11-1.43) and hyperuricemia (OR=2.16, 95%CI: 1.68-2.78) were risk factors for CKD. Conclusion: The prevalence of CKD in adults in Anhui was relatively high and age, gender, BMI, hypertension, diabetes, dyslipidemia and hyperuricemia were found to be associated with the prevalence of CKD. To prevent CKD and its complications, attention should be paid to the management of related risk factors, including overweight and obesity, hypertension, diabetes, dyslipidemia and hyperuricemia.

[microRNA let-7g-3p regulates proliferation, migration, invasion and apoptosis of bladder cancer cells by targeting HMGB2].

OBJECTIVE: To explore the molecular mechanism by which microRNA let-7g-3p regulates biological behaviors of bladder cancer cells. METHODS: The expression levels of let-7g-3p in bladder cancer and adjacent tissues, normal bladder epithelial cells (HUC cells) and bladder cancer cells (T24, 5637 and EJ cells) were detected using qRT- PCR. T24 cells were transfected with let-7g-3p mimic or inhibitor, and the changes in cell proliferation, migration, invasion, and apoptosis were examined. Transcriptome sequencing was carried out in cells overexpressing let-7g-3p, and the results of bioinformatics analysis, double luciferase reporter gene assay, qRT-PCR and Western blotting confirmed that HMGB2 gene was the target gene of let-7g-3p. The expression of HMGB2 was examined in HUC, T24, 5637 and EJ cells, and in cells with HMGB2 knockdown, the effect of let-7g-3p knockdown on the biological behaviors were observed. RESULTS: qRT-qPCR confirmed that let-7g-3p expression was significantly lower in bladder cancer tissues and cells (P < 0.01). Overexpression of let-7g-3p inhibited cell proliferation, migration and invasion, and promoted cell apoptosis, while let-7g-3p knock-down produced the opposite effects. Bioinformatics and transcriptome sequencing results showed that HMGB2 was the key molecule that mediate the effect of let-7g-3p on bladder cancer cells. Luciferase reporter gene assay, qRT-PCR and Western blotting all confirmed that HMGB2 was negatively regulated by let-7g-3p (P < 0.01). Knocking down HMGB2 could partially reverse the effect of let-7g-3p knockdown on the biological behaviors of the bladder cancer cells. CONCLUSION: The microRNA let-7g-3p can inhibit the biological behavior of bladder cancer cells by negatively regulating HMGB2 gene.

[Transcriptomic analysis of the ΔPaLoc mutant of Clostridioides difficile and verification of its toxicity].

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.

[History and present situation of seromuscular flap anastomosis in proximal gastrectomy].

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.