Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo analyze the influencing factors for recurrence in successfully treated pulmonary tuberculosis patients with isoniazid-resistant and rifampicin-sensitive in Shaoxing City, Zhejiang Province. MethodsData on general demographic information, treatment information and drug susceptibility test results for pulmonary tuberculosis patients admitted to the designated tuberculosis medical institutions and registered in the tuberculosis information management system was collected in Shaoxing City from January 2011 to August 2024. A total of 428 patients with isoniazid resistance (including isoniazid single resistance and multiple resistance) but who were successfully treated were included in the study. Information for the recurrence after successful treatment of the patients was analyzed. The Cox proportional hazards models were used to analyze the influencing factors of recurrence in patients. ResultsAmong the 428 successfully treated patients included in the study, 31 cases (accounting for 7.24%) had recurrence by the end of the observation period, with a recurrence rate density of 1.31 per 100 person-years and a median recurrence time of 0.99 (0.08, 8.27) years. Among the relapsed population, 51.61% of the patients relapsed within one year after successful treatment. 77.42% of the patients relapsed within two years after successful treatment. Multivariate Cox regression analysis showed that when isoniazid resistance was discovered, the diagnosis classification of relapse (HR=4.115, 95%CI: 1.734‒9.767) and positive 0-month sequence smear (HR=4.457, 95%CI: 1.053‒18.866) were risk factors for recurrence after successful treatment in patients. ConclusionRegular follow-up should be strengthened for at least two years after the successful treatment of isoniazid-resistant pulmonary tuberculosis patients. Special attention should be paid to the treatment effect and regular re-examination and monitoring after the end of the treatment course of isoniazid-resistant pulmonary tuberculosis patients who have been re-treated and were sputum smear positive at baseline, so as to prevent recurrence and disease progression in high-risk populations.

OBJECTIVE To investigate the effect of salidroside (Sal) on bone loss in obstructive sleep apnea syndrome(OSAS) rats by regulating the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL) pathway. METHODS Rats were randomly divided into(12 rats/group) control group,OSAS group,Sal-L,Sal-M,and Sal-H groups(17.5,35,70 mg/kg). Except for the control group,all other groups were used to replicate the OSAS rat model through hypoxia and reoxygenation cycles. Bone density meters,three-point bending experiments,and Micro CT were applied to measure the bone density,biomechanics,and microstructural changes of the femur in rats. ELISA method was applied to detect serum levels of osteocalcin(BGP),alkaline phosphatase(ALP),and cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-I). RT-PCR was applied to detect OPG and RANKL mRNA levels in the femur. Western blotting was applied to detect the expression of OPG/RANKL pathway proteins in the femur. RESULTS Compared with the control group,the bone density,maximum intensity,maximum load,trabecular bone volume fraction(Tb.BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the OSAS group were decreased,the mRNA and protein expression of CTX-I and RANKL were increased(P<0.05). Compared with the OSAS group,the bone density,maximum intensity,maximum load,Tb.BV/TV,Tb.N,Tb.Th,BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the Sal-L,Sal-M,and Sal-H groups were increased sequentially,the mRNA and protein expression of CTX-I and RANKL were decreased sequentially,the above changes were most great in the Sal-H group(P<0.05). CONCLUSION Salidroside promotes bone formation and inhibits bone resorption by increasing OPG expression and decreasing RANKL expression,thereby reducing bone loss in OSAS rats.

Objective To analyze the expression level of YEATS2 in hepatocellular carcinoma(HCC)about its clinical prognosis and therapeutic value based on biological information from the cancer genome atlas(TCGA)and human protein atlas(HPA)databases.Methods The mRNA expression data and clinical information of HCC were downloaded from the TCGA database,the expression of YEATS2 between HCC tissues and normal tissues was analyzed by using the R software,and the protein expression differences were preliminary verified by the HPA database.The expression differences of YEATS2 between various clinical features of HCC were compared,and their effects on the survival of HCC patients by Kaplan-Meier method and COX regression analysis were then evaluated.Receiver operating characteristic(ROC)curves were plotted to evaluate their diagnostic values.The biological functions of YEATS2 in HCC were analyzed using gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.The relationship between YEATS2 expression and tumor microenvironment(TME)was analyzed by the"ESTIMATE"algorithm,and its relationship with tumor-infiltrating immune cells(TIICs)was assessed by CIBERSORT.Analysis of YEATS2 expression levels to immune checkpoints and drug sensitivity was performed using the R package.Results The expression of YEATS2 was increased in HCC tissues(P=4.96e-21),and its expression level was correlated with age,clinical stage,pathological grade and T stage(all P＜0.05).Overall survival(OS)(P＜0.001)and progression-free survival(FPS)(P=0.016)were decreased in HCC patients with high expression of YEATS2,COX regression results showed that the expression level ofYEATS2 was associated with poor prognosis in HCC patients(OS:HR=2.167,95％CI:1.441～3.261,P=2.06e-04),and it was an independent risk factor for predicting poor prognosis in HCC patients(OS:HR=1.891,95％CI:1.243～2.877,P=0.003).The ROC curve suggested the AUCs for 1,3 and 5 years were 0.677,0.622 and 0.612,respectively,indicating good predictive ability.The TCGA database screened a total of 6 764 differential genes in the YEATS2 high and low expression groups,of which 4 094 genes were up-regulated and 2 670 genes were down-regulated in the YEATS2 high expression group.The results of GO and KEGG enrichment analyses showed that the differentially differentiated genes in the YEATS2 high expression group were mainly enriched in immunoregulation,and cell cycle regulation drug resistance pathway.The results of the TME score showed that the YEATS2 high expression group caused a decrease in immunity score(P＜0.01).The correlation between YEATS2 and TIICs showed that YEATS2 expression was positively correlated with the level of M0-type macrophage infiltration levels(r=0.48,P＜0.001)and 23 immune checkpoint genes(r=0.20～0.46,all P＜0.05),and was negatively correlated with the CD8+T-cells,plasma cells and monocyte(r=-0.26,-0.29,-0.30,P=0.021,0.011,0.008).Drug sensitivity analysis showed that the half maximal inhibitory concentration(IC50)of cabozantinib,lincitinib,doxorubicin,and cyclobenzaprine in patients with high expression of YEATS2 was higher than those in patients with low expression(all P＜0.01).Conclusion YEATS2 was highly expressed in HCC,and the expression level was associated with poor prognosis in HCC patients.YEATS2 can be used as a biomarker for the clinical early diagnosis,prognosis and immunotherapy of HCC,which may provide new ideas for clinical diagnosis and treatment.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective:To analyze the prevention and treatment of Kaschin-Beck disease in Fu County, Shaanxi Province, so as to provide basis for consolidating the results of Kaschin-Beck disease prevention and control and the treatment of patients with Kaschin-Beck disease.Methods:The epidemiological investigation of data and clinical data Kaschin-Beck disease from 1954 to 2022 were collected from the Fu County Institute for Endemic Disease Prevention and Control and People's Hospital of Fu County in Shaanxi Province, respectively. The retrospective study was used to investigate the prevention and control of Kaschin-Beck disease in Fu County through the adoption of comprehensive measures such as relocation, grain exchange, water improvement, conversion of farmland to forest and so on.Results:In 1954, there were 6 endemic townships and 127 endemic villages of Kaschin-Beck disease in Fu County, with a total population of 78 781. A total of 16 327 patients with Kaschin-Beck disease were detected by X-ray examination, with a detection rate of 20.72%, including 5 434 patients without clinical symptoms. There were 5 850 patients with clinical grade Ⅰ, 3 725 patients with clinical grade Ⅱ and 1 318 patients with clinical grade Ⅲ. In 1975, the first general survey of Kaschin-Beck disease was conducted in the whole county, with a total population of 101 341. A total of 9 575 patients with Kaschin-Beck disease were detected by X-ray examination, with a detection rate of 9.45%, including 3 247 cases without clinical symptoms. Among the patients with symptoms, there were 3 704 cases of clinical grade Ⅰ, 2 006 cases of clinical grade Ⅱ and 618 cases of clinical grade Ⅲ. The patients with Kaschin-Beck disease were mainly local residents, accounting for 93.92% (8 993/9 575). In 1997, 27 320 students aged 7 to 16 years in 342 schools of 15 townships were examined and found that there were 169 cases without clinical symptoms with X-ray changes, only 2 cases with clinical grade Ⅰ, and the detection rate decreased to 0.63%. In 1997, Fu County began to encourage relocation and grain exchange to prevent Kaschin-Beck disease. The relocation targets were mainly the seriously ill villages with new cases among children and poor living conditions. By 1999, a total of 100 households and 469 people were relocated, and by 2020, 1 569 households and 5 334 people were relocated. In 1997 and 1998, measures were taken to improve water quality in 43 natural villages in 6 townships, with 1 591 households and 7 375 people benefiting. In 2010, a general survey of Kaschin-Beck disease was conducted in 15 townships of Fu County, with a total population of 135 858, and 3 424 patients with Kaschin-Beck disease were detected by X-ray examination, with a detection rate of 2.52%. There were 2 885 cases with clinical symptoms, including 1 584 cases with clinical grade Ⅰ, 1 024 cases with clinical grade Ⅱ and 277 cases with clinical grade Ⅲ. Among them, 32 561 minors under 16 years old were examined, and 49 patients with Kaschin-Beck disease were detected by X-ray examination, with a detection rate of 0.15%, and all of them were clinical gradeⅠ patients. In 2014, a total of 73 600 people were surveyed in 170 endemic villages of Fu county, and 2 885 patients with Kaschin-Beck disease were detected by X-ray examination, with a detection rate of 3.92%. Compared with 2010, the number of patients with Kaschin-Beck disease increased zero, and there were no underage patients under the age of 16 for 4 consecutive years. By the end of 2016, 666.67 hm 2 of farmland had been converted to forest in Fu County, involving 9 townships (including communities), 33 administrative villages and 1 993 households. In 2018, another general survey of Kaschin-Beck disease was conducted in Fu County, with a total population of 157 362. A total of 2 308 patients were detected by X-ray examination, with a detection rate of 1.47%. Among them, there were 1 270 cases of clinical grade Ⅰ, 870 cases of clinical grade Ⅱ and 168 cases of clinical grade Ⅲ, and there were no patients with Kaschin-Beck disease under 16 years old in the county for 8 consecutive years (2011-2018). In the same year, 22 cases of Kaschin-Beck disease joint replacement were completed in Fu County, and by January 2022, about 60 cases had completed joint replacement. Conclusion:The prevention and control of Kaschin-Beck disease in Fu County has achieved remarkable results through comprehensive measures such as relocation, grain exchange, water improvement and conversion of farmland to forest.

Objective:To investigate the influential factors for poor prognosis in patients with acute myocardial infarction and construct a risk prediction nomograph model.Methods:A total of 173 patients with acute myocardial infarction who received treatment in The First People's Hospital of Huzhou from June 2018 to June 2021 were included in this study. They were divided into a good prognosis group ( n = 130) and a poor prognosis group ( n = 43) according to the follow-up results at 6 months after developing acute myocardial infarction. The clinical data of the two groups were compared using retrospective analysis methods. The potential influential factors were preliminarily screened using LASSO regression analysis. The influential factors of poor prognosis for acute myocardial infarction were investigated using logistic regression analysis. The risk prediction nomograph model was constructed using the "rms" package of R 4.2.6 language. The discriminability, calibration, and effectiveness of the model were evaluated by drawing the receiver operating characteristic curve, calibration curve, and decision curve. Model validation was conducted internally using the Bootstrap method (repeated sampling 1 000 times). Results:There were significant differences in the culprit vessel, Killip classification, vessel opening time, cardiac troponin I (cTnI), hypertension history, N-terminal pro-brain natriuretic peptide (NT-proBNP), diabetes history, creatinine, hyperlipidemia history, left ventricular ejection fraction, smoking history and creatine kinase isoenzymes-MB between the two groups (all P < 0.05). Seven potential influential factors were screened using LASSO regression model, including diabetes history, infarcted vessel anterior descending branch, Killip IV, vascular opening time, cTnI, NT-proBNP, and left ventricular ejection fraction. Logistic regression analysis showed that vascular opening time ( OR = 0.171, 95% CI: 0.053-0.548, P = 0.003), cTnI ( OR = 0.201, 95% CI: 0.079-0.510, P = 0.001), left ventricular ejection fraction ( OR = 1.469, 95% CI: 1.167-1.847, P = 0.001), NT-proBNP ( OR = 0.996, 95% CI: 0.993-1.00, P = 0.025) were independent influential factors of poor prognosis in patients with acute myocardial infarction (all P < 0.05). Linear regression analysis results indicate that the regression model did not exhibit significant multicollinearity (variance inflation factor < 10). Based on the four influential factors identified by logistic regression analysis, a nomogram model for predicting the poor prognosis of patients with acute myocardial infarction was developed. The area under the receiver operating characteristic curve was 0.979 [95% CI (0.959, 0.999)], and the consistency index was 0.934. The calibration curve of the model was close to the ideal curve. Decision curve analysis revealed that when the probability threshold predicted by the model ranged from 0.61 to 0.99, the predictive value of the model was superior. Conclusion:Factors influencing the poor prognosis of acute myocardial infarction include the time of vessel opening, cTnI, NT-proBNP, and left ventricular ejection fraction. The constructed nomogram model demonstrates good efficacy in predicting the poor prognosis of patients with acute myocardial infarction and can provide some reference for clinical doctors and nurses to identify patients with poor prognosis as soon as possible.

Objective:To explore the clinical characteristics of pneumocystis carinii pneumonia (PCP) after kidney transplantation.Methods:From January 2020 to January 2022, clinical data were retrospectively reviewed for 13 renal transplant recipients with pneumocystis pneumonia diagnosed by metagenomics next generation sequencing (mNGS). There were 3 females and 10 males with an age range of (46±10) years.The median time of postoperative onset was 10(2-21) months; The major clinical manifestations included fever ( n=11), cough ( n=7), expectoration ( n=6) and dyspnea ( n=11). Paired t-test was employed for analyzing the laboratory results at admission and discharge. Results:The diagnosis was confirmed by the detection of NGS in alveolar lavage fluid or venous blood.The levels of G test, LDH test, total T lymphocyte absolute count (CD3+ Abs), inhibitory/cytotoxic T lymphocyte count (CD3+ CD8+ Abs) and auxiliary/induced T lymphocyte absolute count (CD3+ CD4+ Abs) were (543.27±440.49) pg/ml, (529.98±222.43)U/L and (191.92±119.42)/μl, (87.33±50.59)/μl and (106.92±87.42)/μl at admission and (69.58±50.21) pg/ml, (285.38±46.62 U/L), (888.58±672.99)/μl, (336.83±305.21)/μl and (520.08±388.76)/μl at discharge.The differences were statistically significant ( P<0.001, P=0.002, 0.006, 0.017, 0.005). All of them received compound sulfamethoxazole and caspofungin.Except for one death due to septic shock after 21-day treatment, 12 cases were cured. Conclusions:mNGS test is one of the important tool for an early diagnosis of PCP.Combined use of compound sulfamethoxazole and caspofungin is an effective anti-infective regimen.And immune function monitoring is vital for adjusting antibiotic and immunosuppressive regimens.