ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

ObjectiveTo evaluate the efficacy of three screening questionnaires for COPD in the community residents of Songjiang District， Shanghai， and to provide a basis for selecting COPD screening questionnaire and process that are more suitable. MethodsCommunity residents aged 40 years or over were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for the study with screening questionnaires and spirometry. Questionnaires included the COPD screening questionnaire （COPD-SQ）， the COPD population screener （COPD-PS） and the revised COPD diagnostic questionnaire （revised-CDQ）. Evaluation of the efficacy of these questionnaires was based on the area under the receiver operating characteristic curve （AUC） of the subjects. DeLong test was used to compare the accuracy of different questionnaires； Z test was used to compare the accuracy of different cut-off values for the same questionnaire. ResultsAmong 3 184 community residents， a total of 259 （8.1%） COPD patients were screened by spirometry. AUC values of these 3 screening questionnaires were >0.7 indicating that they were reliable COPD screening tools. The sensitivity and specificity of the questionnaires at the recommended cut-off values were COPD-SQ （63.7% and 72.2%）， COPD-PS （12.0% and 96.1%）， and revised CDQ （78.8% and 52.7%）， with the COPD-SQ having the highest screening accuracy （AUC=0.754）. The optimal and recommended cut-off values for the three questionnaires differed in this population， but the difference in accuracy was statistically significant only for COPD-PS. The optimal cut-off values for the three questionnaires differed between male and female， and the sensitivity and accuracy of COPD-SQ and COPD-PS improved when lower cut-off values were used for women. The AUC was greater when two questionnaires were utilized simultaneously for screening， but the differences were not statistically significant. ConclusionThe COPD-SQ is recommended for primary COPD screening； a lower cut-off value for women should be considered. The COPD screening questionnaire needs to be further improved for the early diagnosis and treatment of COPD patients.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective:To investigate the application value of porcine small intestinal sub-mucosa (SIS) acellular matrix mesh in laparoscopic inguinal hernia repair (LIHR).Methods:The prospective multicenter randomized controlled single-blind non-inferiority-type study was conducted. The clinical data of 216 patients who underwent LIHR in 4 medical centers, including Beijing Chaoyang Hospital of Capital Medical University et al, from April 2021 to August 2022 were selected. Patients were divided into two groups using a central randomization system. Patients in the experimental group were implanted domestic SIS mesh, and patients in the control group were implanted imported mesh of similar material origin. The baseline characteristics of enrolled patients were evaluated using the full analysis set, and the effectiveness indicators were evaluated using the protocol set. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the ttest. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. If the lower limit of 95% confidence interval( CI) of the difference in effective rates between the experimental group and the control group was greater than the non-inferiority cut-off value of ?10%, the experimental group was considered non-inferior to the control group. Results:(1) Situations of the enrolled patients. A total of 216 patients were selected for eligibility, with 46 patients dropping out due to violation of the trial protocol, and the remaining 170 patients were included in the full analysis set. Nine patients were dislodged due to loss to follow-up, and 161 patients completed follow-up. One case in the experimental group was excluded due to violating the inclusion and exclusion criteria, while the remaining 160 patients were included in the protocol set (80 cases in the experimental group and 80 cases in the control group). There was no significant difference in the gender, age, body mass index (BMI), surgical method, Gilbert type of hernia, volume of intraoperative blood loss, operation time of patients between the experimental group and the control group ( P>0.05), confounding bias ensured comparability. (2) Study endpoints. ① Primary study endpoint. During the postoperative 6 month of follow-up, none of patient in the experimental group or the control group had hernia recurrence, with the recurrence rate as 0. Results of non-inferiority test showed that the difference of hernia recurrence between the two groups was 0 (95% CI as ?4.58% to 4.58%), with the lower limit of ?4.58% greater than the non-inferiority cut-off value of ?10%, which fulfilled the non-inferiority hypothesis. ② Secondary study endpoints. Cases with plasmapheresis during the follow-up were 18 in the experimental group and 29 in the control group, respectively, showing no significant difference between the two groups ( χ2=3.65, P>0.05). There were 4 cases with postoperative pain and 1 case with postoperative malaise in the experimental group, and there were 8 cases with postoperative pain and 0 case with postoperative malaise in the control group, showing no signifi-cant difference in the above indicators between the two groups ( P>0.05). None of patient in the experimental group or the control group had incision infection, enterocutaneous fistula, intestinal obstruction, intestinal canal injury, allergy and rejection, testicular inflammation and/or atrophy, or any other complication. Conclusion:Compared with imported mesh of similar material origin, domestic porcine SIS mesh is safe and effective in LIHR.

Bavachinin is a dihydroflavone isolated from dried ripe fruits of Psoralea corylifolia L.，which has various pharmacological activities, such as anti-tumor, anti-virus, anti-diabetes, anti-inflammatory and neuroprotective, and good potential in clinical applications. With the increasing concern about the safety of P. corylifolia applications in clinical, the bavachinin has been found to be one of the main components causing liver injury. In this paper, the pharmacological activities and hepatotoxicity of bavachinin in the recent 20 years were reviewed, in order to provide reference for the further study and clinical application.

The prevalence and mortality of cancer have been on the rise， and it has been the global leading cause of death. The causes of cancer are diverse， such as heredity， radiation， and carcinogens. The abnormality of cell cycle regulation is also one of the causes. Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides. Cell cycle is highly organized to ensure the integrity of genetic material. This process involves many regulatory genes and proteins. Cell cycle will be dysregulated when these proteins and genes change， resulting in the loss of control of cell proliferation， the inhibition of apoptosis， and finally the occurrence of tumor. At the moment， the therapies for cancer include traditional surgical resection， radiotherapy， chemical therapy， and targeted therapy. Chinese medicine has a wide range of sources and little side effect， which is worthy of further research and development. More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest， so as to improve the quality of life and prolong the survival time of patients with advanced tumors. This article first introduces the characteristics and related regulatory factors of each phase of cell cycle， and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle. Then， we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad， such as Cyclin-dependent kinase （CDK） inhibitors， cell division cycle 25 （CDC25） inhibitors， ataxia-telangiectasia-mutated-and-Rad3-related kinase （ATR） inhibitors， and checkpoint kinase 1 （CHK1） inhibitors. Finally， this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G₀/G₁ phase， S phase and G₂/M phase， in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.

Objective:To analyze the cognitive dysfunction and its influencing factors in patients with multisystem atrophy(MSA).Methods:A total of 143 hospitalized patients with MSA in our hospital from January 2015 to January 2020 were selected as the research objects.The cognitive function was evaluated by Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)scales, meanwhile, the influencing factors of cognitive function were analyzed.Results:The average score of MMSE scale of 143 MSA patients ranged from 9 to 30 points, and the MMSE test identified 86 patients(60.1%)with cognitive impairment, including 58 cases(40.6%)with mild cognitive impairment, 27 cases(18.9%)with moderate cognitive impairment and 1 case(0.7%)with severe cognitive impairment.The average score of MoCA scale of 143 MSA patients ranged from 5 to 30 points, among which 111 cases(77.6%)had cognitive impairment, including 69 cases with mild cognitive impairment(48.3%), 35 cases with moderate cognitive impairment(24.5%)and 7 cases with severe cognitive impairment(4.9%). Both the total scores of MMSE and MoCA scores of MSA patients were not correlated with age of onset, old age, gender, disease duration, type of MSA(MSA-C), orthostatic hypotension(OH), urinary retention, positivity of anal sphincter electromyography(ASEMG), triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), fasting blood glucose and glycosylated hemoglobin, serum uric acid and residual urine volume(all P>0.05). Logistic regression analysis showed that fasting blood glucose was a risk factor for cognitive impairment identified by MMSE( OR=2.224, 95% CI: 1.108-4.462, P=0.024); MSA-C( OR=3.905, 95% CI: 1.302-11.713, P=0.015)and TG( OR=3.494, 95% CI: 1.061-11.501, P=0.040)were risk factors for cognitive impairment identified by MoCA.There were no significant differences in above clinical characteristics between moderate to severe cognitive impairment patients and mild cognitive impairment patients identified by MMSE scale( P>0.05). Similarly, there were no significant differences in the above clinical characteristics between moderate to severe cognitive impairment patients and mild cognitive impairment patients by MoCA scale( P>0.05). Logistic regression analysis showed that TG was a risk factor for moderate to severe cognitive impairment identified by MMSE( OR=17.624, 95% CI: 2.596-119.669, P=0.003), while TC was a protective factor( OR=0.006, 95% CI: 0.000-0.714, P=0.036). Logistic regression analysis did not find the influencing factors of moderate to severe cognitive impairment as suggested by MoCA score. Conclusions:There is a high incidence of cognitive impairment in MSA patients.The type of MSA(MSA-C), blood glucose and blood lipid may be influence factors of cognitive impairment in MSA patients.Age of onset, old age, gender, disease duration, autonomic dysfunction, and uric acid have no significant correlation with cognitive impairment of MSA.