BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

In situ tumor vaccine has become an important strategy in cancer immunotherapy owing to its ability to induce immune responses locally and overcome tumor heterogeneity. However, the abnormal structure and mechanical properties of the tumor’s physical microenvironment significantly limit the efficiency of vaccine delivery and immune efficacy. In this review, the key factors in the tumor’s physical microenvironment, including solid pressure, interstitial fluid pressure, matrix stiffness, and tissue microstructure, are systematically discussed. Their obstructive roles in immune cell infiltration, antigen presentation, and immune activation are analyzed. The potential of approaches, such as radiotherapy, anti-angiogenic therapy, extracellular matrix degradation agents, nanomaterials, and hydrogel delivery platforms, in reshaping the tumor’s physical microenvironment is explored. This review aims to offer theoretical and practical guidance for optimizing in situ vaccine strategies through the regulation of the tumor’s physical microenvironment, ultimately advancing the precision and effectiveness of cancer immunotherapy.

Objective To investigate the prevalence of Cryptosporidium infection and the distribution of parasite species and genotypes among HIV-positive individuals in Jiangxi Province. Methods HIV-positive individuals' sociodemographic and clinical data were collected from three AIDS designated hospitals in Jiangxi Province from January 2022 to March 2023. Subjects' stool samples were collected, and genomic DNA was extracted from stool samples. Nested PCR assay was performed based on the small subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium, and Cryptosporidium gp60 gene was amplified in stool samples positive for the SSU rRNA gene. The second-round PCR amplification product was checked with 1.5% agarose gel electrophoresis, and the products of suspected positive amplifications were sequenced, followed by sequence alignment. The phylogenetic tree was created using the Neighbor-Joining method with the software MEGA 11.0, to characterize the species, genotypes and sub-genotypes of Cryptosporidium. Results A total of 382 HIV-positive individuals were enrolled, with two cases identified with Cryptosporidium infection (0.52% prevalence), and both cases had no abdominal pain or diarrhea. Following sequencing and sequence alignment, the gene sequences of these two Cryptosporidium isolates shared 99.76% and 99.88% similarity with the gene sequence of C. meleagridis isolates. Phylogenetic analysis based on the Cryptosporidium SSU rRNA gene sequence identified the species of these two Cryptosporidium-positive stool samples as C. meleagridis. Following nested PCR amplification of the Cryptosporidium gp60 gene, sequencing and sequence alignment, the two C. meleagridis isolates were characterized as III eA17G2R1 and III bA25G1R1a sub-genotypes, and the sub-genotype III bA25G1R1a was firstly described in humans. Conclusion The prevalence of Cryptosporidium is low among HIV-positive individuals in Jiangxi Province. The likelihood of Cryptosporidium infection cannot be neglected among HIV-positive individuals without diarrhea.

Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

Objective To establish a clinical-CT model,and to observe its value for evaluating lymphovascular invasion(LVI)and/or perineural invasion(PNI)in esophageal squamous cell carcinoma(ESCC).Methods Data of 156 ESCC patients were retrospectively analyzed.The patients were divided into positive group(n=58,LVI[+]and/or PNI[+])and negative group(n=98,LVI[-]and PNI[-])according to postoperative pathological results.Clinical and CT data were compared between groups.Logistic regression analysis was performed to establish a model,and its efficacy of evaluating ESCC LVI and/or PNI was analyzed.Results Significant differences of carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),tumor thickness,tumor volume and CT venous phase value(CTV),the difference between CTV and CT plain phase value(CTP)(△CTV-P)and venous phase enhancement rate(V％)were found between groups(all P＜0.05),and the area under the curve(AUC)of the above parameters for evaluating ESCC LVI and/or PNI was 0.702,0.690,0.731,0.744,0.621,0.631 and 0.599,respectively.CEA,CA199,tumor thickness,tumor volume and CTV were all independent predictive factors for ESCC LVI and/or PNI.A combined model was established based on the above features,and its accuracy,sensitivity and specificity for evaluating ESCC LVI and/or PNI was 82.05％,65.52％and 91.84％,respectively,with AUC of 0.838,higher than that of each single parameter(all P＜0.05).Conclusion The established clinical-CT model could effectively evaluate ESCC LVI and/or PNI.

Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

Objective: To explore the chain mediating effect of regulatory emotional self efficacy and positive psychological capital on resilience and the mental health of college students. Methods: A total of 809 college students of Chaohu University were selected and were administered with the the Self report Symptom Invertory, Symptom Checklist,90 (SCL-90), Connor Davidson Resilience Scale (CD-RISC), Regulatory Emotional Self efficacy Scale (RES-C) and Positive Psychological Capital Questionnaire (PPQ). Multiple linear regression analysis was performed, taking resilience, regulatory emotional self efficacy and positive psychological capital as independent variables and the mental health of college students as dependent variables, meanwhile test the intermediary effect. Results: Differences were found in resilience(3.52±0.55,3.27±0.42), regulatory emotional self efficacy(3.58± 0.59 ，3.32±0.57), positive psychological capital(4.74±0.77，4.49±0.76) and mental health(158.66±33.01，176.53±34.73) among college students with different sources(urban and rural)( t =55.82，39.22，21.28，-54.14， P <0.05). Resilience, regulatory emotional self efficacy and positive psychological capital were significantly associated with the severity of mental health of college students( R 2= 0.21, P <0.01). Regulatory emotional self efficacy and positive psychological capital played a significant chain mediating role between resilience and poor mental health( effect =-0.03, P <0.05), and the mediating effect accounted for 39.3% of the total effect. Conclusion The mental health of college students can be improved by strengthening levels of resilience and enhancing regulatory emotional self efficacy, and constructing positive psychological capital could contribute to the association between resilience and mental health.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Objective: This study aimed to explore the feasibility of functional evaluation of the lateral pterygoid muscle (LPM) using diffusion tensor imaging (DTI) in patients with temporomandibular joint disorders (TMDs). Materials and Methods: A total of 119 patients with TMD (23 male and 96 female; mean age ± standard deviation, 41 ± 15 years; 58 bilateral and 61 unilateral involvements for a total of 177 joints) and 20 healthy volunteers (9 male and 11 female;40 ± 13 years; 40 joints) were included in this prospective study. Based on DTI of the jaw in the resting state, the diffusion parameters, apparent diffusion coefficient (ADC), fractional anisotropy (FA), λ1, λ2, and λ3 of the superior and inferior heads of the LPM (SHLPM and IHLPM) were measured. Patients with TMD with normal disc position (ND), anterior disc displacement with reduction (ADWR), and anterior disc displacement without reduction (ADWOR) were compared. Results: Patients with TMD overall, and ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 in both the SHLPM and IHLPM than those in volunteers (p < 0.05 for all), whereas the ND subgroup only had significantly higher ADC and λ1 (p < 0.001). Meanwhile, significant differences in FA in the SHLPM and IHLPM were found between volunteers and ADWOR (p = 0.014 and p = 0.037, respectively). Among the three TMD subgroups, except for λ3 and FA in the ADWR subgroup, ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 and lower FA than those in the ND group (p < 0.050). There was no significant difference in diffusion variables between ADWR and ADWOR. In ADWOR, the osteoarthritis group had significantly higher λ3 and lower FA values in the IHLPM than those in the non-osteoarthritis group. Conclusion DTI successfully detected functional changes in the LPM in patients with TMD. The unsynchronized diffusivity changes in the LPM in different subgroups of TMD signified the possibility of using diffusion parameters as indicators to identify the severity of LPM hyperfunction at various stages of TMD.