To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions.

Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation. METHODS: A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241). RESULTS: MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c.1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c.2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+PM2_Supporting+PM3+PP1) and likely pathogenic (PM2_Supporting+PM3+PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
Humans ; Male ; Pedigree ; Cholestasis, Intrahepatic/diagnostic imaging* ; Adenosine Triphosphatases/genetics* ; Female ; Adult ; Exome Sequencing ; Mutation ; East Asian People

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective:To explore the risk factors of pneumoconiosis complicated with pulmonary tuberculosis, to construct a clinical prediction model for patients with pneumoconiosis complicated with pulmonary tuberculosis, and to provide a scientific basis for the prevention of pneumoconiosis complicated with pulmonary tuberculosis.Methods:In January 2024, a total of 232 patients with pneumoconiosis (including coal workers' pneumoconiosis and silicosis) who were treated in the Department of Respiratory and Critical Care Medicine of the Third People's Hospital of Xinjiang Uygur Autonomous Region (Xinjiang Uygur Autonomous Region Occupational Disease Hospital) from January 2022 to January 2023 were randomly selected as the study subjects. Collectted basic patient information and diagnostic data. Multivariate logistic regression analysis was used to screen the risk factors related to pneumoconiosis complicated with pulmonary tuberculosis. According to the results of multivariate logistic regression analysis, a nomogram was established, and the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive ability.Results:Among the 232 patients with pneumoconiosis, 73 were complicated with pulmonary tuberculosis, accounting for 31.47% (73/232). Multivariate logistic regression analysis determined that dust exposure time, type of work, smoking history, and lung function level were all risk factors for pneumoconiosis complicated with tuberculosis ( OR=10.33, 95% CI=1.92~55.66, OR=5.43, 95% CI=1.91~15.44, OR=3.10, 95% CI=1.15~8.37, OR=4.00, 95% CI=1.62~9.87; P<0.05). The constructed nomogram model has good clinical applicability when the area under the receiver operating characteristic (ROC) curve is 0.77 [95% CI (0.69, 0.73) ], the calibration curve is close to the ideal diagonal, the absolute error between the simulation curve and the actual curve is 0.03, and the DCA decision curve shows that the probability threshold of the nomogram model is 1%-90%. Conclusion:The risk of pneumoconiosis complicated with tuberculosis is high, and the risk factors of dust exposure time, smoking history, type of work and lung function level are high. This nomogram model can be used to predict the risk of pulmonary tuberculosis in patients with pneumoconiosis, which is helpful for early intervention.

This study aims to establish an indirect ELISA method for detecting RVFV antibodies u-sing recombinant proteins of Rift Valley fever virus(RVFV)Gn protein Ⅱ-Ⅲ structural domains as the encapsulated antigen which was expressed by the Escherichia coli(E.coli)expression sys-tem.The gene sequences encoding the Ⅱ and Ⅲ subdomains of RVFV Gn protein were inserted in-to pET-30a(+)to construct the recombinant plasmid pET-RVFV Gn-D Ⅱ-Ⅲ.After transforma-tion of the recombinant plasmid into DE3(BL21)competent cells,the recombinant Gn-D Ⅱ-Ⅲ protein was induced with IPTG and purified using affinity chromatography.An indirect ELISA method for the detection of RVFV antibodies was developed using purified recombinant protein as coating antigen and SPA-HRP as the enzyme-labelled secondary antibody.Western blot analysis confirmed that the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed.The optimal expression conditions for RVFV Gn-D Ⅱ-Ⅲ protein were induced with 0.8 mmol/L IPTG at 37 ℃ for 5 h.The Gn-D Ⅱ-Ⅲ protein was purified using affinity chromatography with a purity of 91.9％,and the purified protein was used as the encapsulated antigen to develop an ELISA assay for RVFV anti-bodies.The specificity evaluation showed that the method specifically detected RVFV-positive sera and did not cross-react with sera positive for West Nile virus(WNV),Ebola virus(EBOV),Mar-burg virus(MARV)and tick-borne encephalitis virus(TBEV).When the RVFV Gn-D Ⅲ-Ⅲ posi-tive serum was diluted to 6 400 times,the test result still showed positive results,demonstrating the method had good sensitivity.The repeatability evaluation results indicated that the variation co-efficients for both intra-and inter-batch responses was less than 10％,indicating that the method had good repeatability.In conclusion,the RVFV Gn-D Ⅱ-Ⅲ protein was successfully expressed u-sing the E.coli expression system.The purified recombinant Gn-D Ⅱ-Ⅲ protein was used as the encapsulated antigen to develop an indirect ELISA assay for RVFV antibodies,which provides a preliminary basis for the diagnosis of RVF and the research and development of RVF vaccines.

To establish an indirect enzyme linked immunosorbent assay(ELISA)method for the detection of Zaire Ebola virus(ZEBOV)specific antibodies,the full-length of ZEBOV GP1 gene was amplified by PCR and cloned into pET-30a(+)vector to generate the pET-30a(+)-GP1 plasmid.After expressed in the E.coli expression system,the purified GP1 protein was used as coating antigen to establish the indirect ELISA method for detection of ZEBOV antibody.The con-ditions including concentration of coating antigen and serum dilution were determined by chess-board titration.Specificity,sensitivity,and reproducibility of the established ELISA detection meth-od were evaluated.GP1 protein was successfully prepared by prokaryotic expression,and was used as the coatingantigen for indirect ELISA.By optimizing the reaction conditions,the optimal concen-tration of the coating antigen was determined to be 0.5 g/L;the optimal dilution of serum was cal-culated to be 1∶3 200;the optimal dilution of enzyme-labeled secondary antibody was measured to be 1∶20 000.The established method exhibited excellent specificity,sensitivity,and reproducibili-ty.In the present study,the GP1 protein was successfully expressed in the E.coli expression sys-tem and the high purity GP1 protein was used as the coating protein to establish an indirect ELISA assay for ZEBOV antibody.This method is highly specific,sensitive,and reproducible,which provides technical support for the fur-ther study of the biological function of GP1 and the detection of ZEBOV antibody in serum.

Due to the specificity of radiopharmaceuticals for targeted α radionuclide therapy, such as radioactivity and radiation damage risk, it is necessary to estimate the internal radiation dose in preclinical evaluation to correctly evaluate the efficacy and safety of the drug, as well as in subsequent clinical studies. This review illustrates current research status of estimating internal radiation dose of targeted α radionuclide therapeutic radiopharmaceuticals based on preclinical studies, in order to add insights for understanding estimation of radiopharmaceuticals internal radiation dose and provide reference for the preclinical evaluation of radiopharmaceuticals.

Objective:To observe the effect of exercise-regulated miR-344g-5p on the fibrosis-related SMAD genes and transforming growth factor beta (TGF-β) in the myocardia of mice modeling diabetes.Methods:Twenty-four male C57BL/6 mice (6-8 weeks old) were randomly divided into a control group ( n=12) and a type 2 diabetes group ( n=12). Each group was further divided into two subgroups based on exercise status to form a sedentary control group, an exercise control, a sedentary type 2 diabetes group and an exercise type 2 diabetes group with six mice in each subgroup. The control groups were fed a normal diet, while the type 2 diabetes groups were on a high-fat diet for 12 weeks. Type 2 diabetes was then induced by intraperitoneal injection of streptozotocin. Two weeks later, the exercise groups began 40 minutes of daily swimming training, five days a week for eight consecutive weeks. Right after that, their cardiac function was measured using a small animal ultrasound system and the derived ejection fraction (EF) and the maximal early (E) and late (A) transmitral velocities ratio (E/A ratio) in diastole. They were then sacrificed and myocardial tissue was resected and stained with Sirius red. The expression of miR-344g-5p in the myocardium was detected using quantitative polymerase chain reactions. The expression of phosphorylated SMAD3 (p-SMAD3) and TGF-β were assessed using western blotting. The Target Scan database was exploited to analyze whether there were predicted targets of miR-344g-5p and pro-fibrotic genes such as SMAD3, TGFBR2, COL1A2 and COL12A1, and to determine any correlations in the gene regulation. Results:After 22 weeks, the EF and E/A ratio in the sedentary type 2 diabetes group were (57.5±4.1)% and (1.4±0.3), respectively, both significantly lower than in the other groups. Myocardial collagen fibers in the sedentary type 2 diabetes group were significantly more abundant than in the sedentary control and exercise type 2 diabetes groups. And miR-344g-5p expression in the myocardia of the exercise type 2 diabetes group was significantly greater than that in the sedentary type 2 diabetes group. The expression of p-SMAD3 and TGF-β in the myocardia of the sedentary type 2 diabetes group was significantly higher than in the sedentary control and exercise type 2 diabetes groups. Target Scan analysis revealed that miR-344g-5p had potential binding sites with several fibrosis-related genes such as SMAD3, TGFBR2, COL1A2, and COL12A1. Based on the reduction in TGF-β and p-SMAD protein expression in the exercise type 2 diabetes group, it was hypothesized that miR-344g-5p may inhibit the post-transcriptional processes of those genes.Conclusions:Exercise promotes the recovery of diabetic cardiomyopathy by upregulating myocardial miR-344g-5p expression, which subsequently targets and suppresses p-SMAD3 and TGF-β protein expression, thereby reducing diabetic myocardial fibrosis.

Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.