OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2, psbA-trnH, matK as universal barcode sequences, and DX, HH, JYH as specific barcode sequences, to identify the authenticity of commercial medicinal and food homology scented herbal teas. The aim was to investigate the authenticity of scented herbal tea products circulating in the market. The research results revealed that among 180 scented herbal tea samples, DNA barcodes were successfully obtained from 164 samples, while the remaining samples either lacked the target components or suffered severe DNA degradation, resulting in failed amplification. Combined with morphological identification studies, it was found that out of the 180 samples, 141 were authentic, accounting for 78.33% of the total samples, while 31 samples showed adulteration and 8 samples lacked the target components, accounting for 21.67% of the total samples. Additionally, water testing revealed that 5 samples of Carthamus tinctorius herbal tea exhibited the phenomenon of weight adulteration. This study exposed the presence of adulteration and weight adulteration in scented herbal tea products, highlighting the need for regulatory authorities to expedite the establishment of quality standards in scented herbal tea industry. These findings provide valuable insights for the rapid development of the scented herbal tea industry.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab monotherapy in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC），so as to provide reference for rational use of drug in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China’s health system， based on the data of RATIONALE-302 study，with simulation time limit of 10 years， cycle period of 1 month. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life year （QALY） as utility index. The cost-effectiveness of tislelizumab monotherapy was compared with that of chemotherapy for second-line treatment of advanced or metastatic ESCC by cost-utility analysis. The stability of basic analysis results was validated through sensitivity analysis and scenario analysis. RESULTS The results of basic analysis showed that compared with chemotherapy group， incremental cost per capita of tislelizumab group was 35 025.32 yuan，and incremental utility per capita was 2.71 QALYs； ICER was 12 892.31 yuan/QALY， which was far lower than the willingness-to-pay （WTP） threshold of 3 times of China’s per capita gross domestic product （GDP） 242 928 yuan in 2021. The results of univariate sensitivity analysis showed that parameters such as the cost of apatinib， the utility value of disease progression status and the cost of adverse reactions in the chemotherapy group had a great impact on the ICER value， but these parameters could not cause the reversal of the basic analysis results. Probabilistic sensitivity analysis showed that WTP threshold was higher than 80 000 yuan/QALY，the probability of tislelizumab monotherapy possessed cost-effectiveness was 100%. Results of scenario analysis showed that in which model simulation time lasted for 5 or 20 years，ICER of tislelizumab was 8 331.00 yuan/QALY and 12 981.00 yuan/QALY， which were less than 3 times of China’s per capita GDP in 2021 as WTP threshold. CONCLUSIONS When three times of China’s GDP per capita in 2021 is taken as the WTP threshold， the second-line treatment of tirelizumab monotherapy for advanced or metastatic ESCC is more cost-effective than chemotherapy.