ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Objective To investigate the expression of the circular RNA circ-PHC3 in cervical cancer tissues and its regulatory mechanisms in the proliferation,migration,and invasion of cervical cancer cells.Methods The expression levels of circ-PHC3 in cervical cancer tissues and adjacent non-tumor tissues were analyzed using the GEO database.The correlation between circ-PHC3 expression and the clinical stage as well as prognosis of cervical cancer patients was also evaluated.The expression of circ-PHC3 in cervical cancer cell lines HCC94,C33A,HeLa,HCC1106,and SiHa was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The cell line with the highest circ-PHC3 expression was selected for transfection with a circ-PHC3 inhibitor.The interaction between circ-PHC3 and miR-1179 was validated using a dual luciferase reporter gene assay.The expression levels of miR-1179 in transfected cells were further assessed by qRT-PCR.Functional assays,including colony formation,flow cytometry,wound healing,and Transwell assays,were conducted to evaluate cell proliferation,cell cycle progression,migration,and invasion,respectively.Western blot analysis was performed to determine the expression of key proteins associated with proliferation,migration,and invasion in circ-PHC3-modulated cells.Finally,in vivo experiments were carried out to investigate the impact of circ-PHC3 silencing on the growth and metastasis of cervical cancer cells in animal models.Results The expression level of circ-PHC3 in cervical cancer tissues was significantly higher than that in adjacent normal tissues(P<0.01).Furthermore,circ-PHC3 expression was significantly associated with the clinical stage of cervical cancer(P<0.01).Patients with high circ-PHC3 expression exhibited a notably lower survival rate compared to those with low circ-PHC3 expression(P<0.01).In cervical cancer cell lines including HCC94,C33A,HeLa,HCC1106,and SiHa,circ-PHC3 expression was markedly upregulated(all P<0.01),with the highest expression observed in HCC1106 cells(P<0.01).Circ-PHC3 was found to directly interact with miR-1179(P<0.01),and silencing circ-PHC3 significantly increased miR-1179 expression(P<0.01).Transfection of HCC1106 cells with a circ-PHC3 inhibitor significantly suppressed cell proliferation,migration,and invasion(all P<0.01),and induced cell cycle arrest(P<0.01);these effects were partially reversed by co-transfection with a miR-1179 inhibitor(all P<0.05).In HCC1106 cells with circ-PHC3 knockdown,the expression levels of key proteins associated with proliferation,migration,and invasion—Cyclin E,CDK2,MMP-9,and N-cadherin—were significantly reduced(all P<0.01),and this reduction was partially attenuated by miR-1179 inhibition(all P<0.01).In vivo experiments further demonstrated that circ-PHC3 knockdown significantly inhibited tumor growth and metastasis of HCC1106 cells(all P<0.01).Conclusions Circ-PHC3 is highly expressed in cervical cancer tissues,and its overexpression is significantly correlated with poor prognosis in patients with cervical cancer.Knockdown of circ-PHC3 upregulates the expression of miR-1179 and suppresses the proliferation,migration,and invasion of cervical cancer cells.

Objective To investigate the factors influencing the development of extra-pulmonary tuberculosis(EPTB)in patients with viral hepatitis complicated by pulmonary tuberculosis(PTB).Methods A retrospective analysis was conducted on 427 patients with Hepatitis B Virus(HBV)and Hepatitis C Virus(HCV)infections complicated by PTB admitted to the tuberculosis department of Kunming Third People's Hospital from January 2015 to December 2020.Patients were divided into the EPTB complication group(n=72)and the non-EPTB complication group(n=355)based on the presence of EPTB.Clinical treatment data of patients were collected.Univariate and multivariate Logistic regression analyse were used to screen independent risk factors for EPTB as predictive factors.A nomogram prediction model was established for Extrapulmonary Tuberculosis(EPTB)complications in patients with viral hepatitis and Pulmonary Tuberculosis(PTB),evaluated using the Hosmer-Lemeshow test and ROC curve analysis.Results Among the 427 patients,292(68.3%)were male and 135(31.7%)were female,with 72 cases of EPTB,resulting in an incidence rate of 16.86%.In the EPTB group,there were 34 males(47.2%)and 38 females(52.8%).The types of EPTB included tuberculous pleuritis(21 cases,29%),tuberculous peritonitis(16 cases,22%),lymph node tuberculosis(13 cases,18%),tuberculous encephalitis(5 cases,6%),intestinal tuberculosis(6 cases,8%),bone tuberculosis(5 cases,6%),pelvic tuberculosis(3 cases,4%),and genitourinary tuberculosis(3 cases,4%).Multivariate logistic regression analysis showed that gender(OR=0.425,95%CI:0.250-0.722,P=0.02),low triglyceride(TG)levels(OR=0.837,95%CI:0.717-0.978,P=0.025),the tuberculosis-specific antigen A(ESAT-6)(OR=1.007,95%CI:1.003～1.011 were independent influencing factors for EPTB in patients with PTB complicated by HBV and HCV infections.The optimal cutoff value for the nomogram model is 0.192,with a sensitivity of 0.611,specificity of 0.710,Youden index of 0.741,positive likelihood ratio of 2.103,and negative likelihood ratio of 0.548.The Hosmer-Lemeshow test yielded χ2=2.631,P=0.955.ROC curve analysis showed an AUC of 0.693,95%CI:0.629 1～0.7574.Conclusion The prediction model based on gender,low TG levels and ESAT-6 can well predict the occurrence of EPTB to some extent,providing a reference for clinical treatment.

Objective To evaluate the relationship between nutritional parameters and the risk of venous thromboembolicism(VTE)in patients with tuberculosis so as to identify the risk factors and predictors of thrombosis and assist in the early identification of high-risk factors for VTE in patients with the pulmonary tuberculosis.Methods A total of 323 patients diagnosed with the pulmonary tuberculosis and hospitalized in Kunming Third People's Hospital from August 2021 to August 2023 were collected.According to the VTE risk assessment of non-operative patients,they were divided into the high-risk group and the low-risk group respectively with 116 and 207 in each group.The nutritional indicators with statistically significant differences between the two groups were screened by Lasso regression.Multivariate Logistic regression was used to screen the independent risk factors for high VTE risk in pulmonary tuberculosis patients,and a nomogram prediction model was constructed.The prediction model was evaluated by receiver operating characteristic curve(ROC),calibration curve,decision curve,and influence curve.Results Patients in the high-risk group were significantly older than those in the low-risk group(59 vs.41,P<0.001),hypertension,gender,and Type 2 diabetes did not differ significantly(P values were 0.084,0.724 and 0.488,respectively).9 variables were selected from the inter-group comparison and Lasso regression,including ALB,HCT,NRS2002 scores,HBDH,RDW-SD,RDW-CV,TG,CONUT scores,and NEFA.Multivariate Logistic regression analysis showed that ALB,NRS2002 scores,RDW-SD,and CONUT scores were independent influencing factors for the high risk of VTE scores in patients with tuberculosis(P<0.005).Area under the ROC curve showed that the AUC(0.892)for high-risk VTE scores in patients with the pulmonary tuberculosis was greater than that of ALB(0.803),NRS2002 score(0.735),RDW-SD(0.685),and CONUT score(0.774).Fitting prediction model:Logit(P):Y=0.433×NRS-0.136×ALB+0.411×CONUT score+0.072×RDW-SD-1.770,P=1/(1+e-Y)(Y:prediction index,P:prediction probability).Calibration curve showed that the model prediction tended to be consistent with the actual results(U:>0.05),and the decision curve and influence curve showed that the model can bring clinical benefits.Conclusion ALB,NRS2002 scores,RDW-SD,and CONUT scores are independent influencing factors for the high risk of VTE scores in patients with tuberculosis.They can guide the clinical practice,improve these indicators as soon as possible,reduce VTE scores,and reduce the thrombosis risk.At the same time,the prediction model performs well in the verification cohort,with its discrimination ability,calibration accuracy and clinical utility(decision curve analysis)all reaching a satisfactory level.

AIM:This study aims to explore the mechanisms of influenza A virus(IAV)-induced macrophage inflammatory injury based on the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling loop and investigate the intervention effects of Ma-Xing-Shi-Gan decoction(MXSGD)-medicated serum.METHODS:RAW264.7 and BV2 cells were divided into control,Janus kinase(JAK)/STAT signaling pathway activator,inhibitor,model,oseltamivir,antiviral particle,and MXSGD groups.After IAV modeling and serum interventions,the cells were cultured for 24 and 48 h,and the indicators were detected and analyzed.ELISA,RT-qPCR,Western blot,and immuno-fluorescence assay were used to detect the secretion levels of IL-6 in the cell culture supernatant,IL-6 and STAT3 mRNA expressions,protein expression of STAT3,and expression levels of phosphorylated STAT3(p-STAT3),respectively.Pearson correlation analysis was used to evaluate the correlation between p-STAT3 and IL-6 in the two cell types.A co-cul-ture model of the two cells was constructed,and the secretion levels of IL-6 in the cell culture supernatant was measured.Molecular docking analyses were performed for STAT3 and MXSGD.RESULTS:After IAV simulation,the secretion lev-els of IL-6 in the cell culture supernatant,mRNA expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in both cell lines were elevated(P<0.05 or P<0.01).Pearson correlation analysis revealed that p-STAT3 expression was positively correlated with IL-6 expression.The secretion levels of IL-6 in the co-culture model in-creased(P<0.01).MXSGD down-regulated the secretion levels of IL-6 in the cell culture supernatant mRNA,expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in two kinds of cells(P<0.05 or P<0.01),and inhibited the secretion levels of IL-6 in co-culture models.STAT3 demonstrated good binding energies for liquiritin,amygdalin,and ephedrine.CONCLUSION:IAV can induce inflammatory injury in macrophages,and its mechanism may be related to activation of the IL-6/STAT3 signaling loop.MXSGD may alleviate the pathogenic effects of IAV by modulating the signaling loop.

Objective:To describe the prevalence of perinatal death in Tongzhou District of Beijing,and to estimate the association between maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid and perinatal mortality rate.Methods:A retrospective cohort study was conducted based on the maternal and child care system in Tongzhou District of Beijing.The subjects were 94 490 perinatal who were born during January 2013 to December 2018.The information on perina-tal outcomes and maternal periconceptional supplementation of folic acid or multiple micronutrients contai-ning folic acid were collected.The Poisson log-linear model was used to estimate the association between maternal periconceptional folic acid or multiple micronutrients supplementation and perinatal mortality rate.Results:The overall perinatal mortality rate was 2.71‰.The perinatal mortality rates for maternal nutrients supplementation containing folic acid and no supplementation during periconceptional period were 2.63‰ and 3.43‰,respectively,and the difference in rates was not statistically significant[crude risk ratio(cRR)=0.77,95％CI:0.54-1.14].After adjusting for potential confounding factors in-cluding ethnicity,age,education level,occupation,household registration,parity,numbers of fetuses,gestational age,pregnant with assisted reproductive technology,delivery year and pre-pregnancy body mass index,the rates remained not statistically significant[adjusted risk ratio(aRR)=0.93,95％CI:0.77-1.13].The perinatal mortality rates were 2.23‰ and 2.99‰ for pure folic acid and multi-nutrients supplements containing folic acid,respectively,and the difference in rates was statistically sig-nificant(cRR=1.34,95％CI:1.02-1.76).The rates difference remained statistically significant after adjusting for potential confounders(aRR=1.31,95％CI:1.06-1.62).Additionally,the peri-natal mortality rates differences among the non-supplementation group and the supplementation group with variate timing of initiation(pre-conception or post-conception)or frequency of supplementation(low-frequency or high-frequency)were not statistically significant,regardless of adjusting for confounders.Conclusion:The overall perinatal mortality rate was lower than the national average level in Tongzhou District of Beijing.Maternal periconceptional supplementation of pure folic acid or micronutrients contai-ning folic acid had no impact on perinatal mortality.The association between maternal periconceptional supplementation of multiple micronutrients containing folic acid and perinatal mortality rate need further research.

Objective:To investigate the changes of respiratory function and lung volume after bariatric surgery using spiral CT three-dimensional imaging technology.Methods:Using the prospective study method, the medical records of 30 subjects undergoing sleeve gastrectomy (LSG) in the Eighth Department of General Surgery, the Second Hospital of Hebei Medical University from Jan. 2023 to Jun. 2024 were collected. Among them, 12 were males and 18 were females, aged from 20 to 45 years, with the average age of 31.1 years old. Chest CT scans were completed within 1 week before surgery and 6 months after surgery. The subject′s CT plain scan reconstructed thin-layer images of the mediastinal window were transferred to a GE workstation, and the lung volumes of both lungs and each lobe and the tracheal wall area of the five bronchial segments (RB1, RB4, RB10, LB1 + 2 and LB10) were calculated as a percentage of the airway cross-sectional area (WA%), and the posterior intercostal position corresponding to the diaphragm was recorded. Paired t-test and rank-sum test were used to compare preoperative and postoperative differences.Results:Compared with pre-operation, the subject′s body mass index decreased significantly 6 months after bariatric surgery [(42.22±7.31) kg/m 2vs (30.12±5.59) kg/m 2,t=7.31, P<0.001)]. Except for left lower lobe [(1.15±0.23) L vs (1.27±0.24) L, t=1.97, P=0.054] and right middle lobe [(0.57±0.16) L vs (0.83±0.16) L, t=1.38, P=0.172], the remaining lung parts were significantly larger after surgery than before surgery: right upper lobe [(0.80±0.17) L vs (0.94±0.19) L, t=2.79, P=0.007], right lower lobe [(1.08±0.14) L vs (1.22±0.19) L, t=3.23, P=0.002], left upper lobe [(1.12±0.20) L vs (1.24±0.23) L, t=2.26, P=0.014]. Overall, right lung volume [(2.44±0.33) L vs (2.79±0.41) L, t=3.62, P=0.001], left lung volume [(2.27±0.36) L vs (2.52±0.39) L, t=2.53, P=0.014] and total lung volume [(4.71±0.60) L vs (5.30±0.71) L, t=3.48, P=0.001] all increased significantly at 6 months after surgery compared with before surgery. All five segments of bronchus (WA%) were significantly reduced after surgery than before surgery: RB1: [(62.82±4.66) vs (66.85±3.99), t=3.60, P=0.001]; RB4: [(61.24±5.28) vs (64.31±5.51), t=2.20, P=0.031]; RB10: [(60.03±4.64) vs (62.97±5.73), t=2.18, P=0.033]; LB1+ 2: [(63.61±5.05) vs (67.90±4.30), t=3.54, P=0.001]; LB10: [(58.73±6.49) vs (62.01±5.06), t=2.17, P=0.034)]. The posterior intercostal position corresponding to the diaphragm dropped from an average of 7-8 intercostal spaces to 8-9 intercostal spaces, with a significant difference (rank mean 22.77 vs 38.23, Z=-3.67, P<0.001). Conclusion:Bariatric surgery can significantly reduce weight, reduce the pressure of chest and abdominal, improve lung compliance, reduce the internal pressure of the chest, lower the diaphragm, expand the lung volume and airway cross-sectional area, restore the original airway anatomy and respiratory physiology, so it can effectively improve the respiratory function and lung structure abnormalities caused by obesity.

Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

Objective:To describe the prevalence of perinatal death in Tongzhou District of Beijing,and to estimate the association between maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid and perinatal mortality rate.Methods:A retrospective cohort study was conducted based on the maternal and child care system in Tongzhou District of Beijing.The subjects were 94 490 perinatal who were born during January 2013 to December 2018.The information on perina-tal outcomes and maternal periconceptional supplementation of folic acid or multiple micronutrients contai-ning folic acid were collected.The Poisson log-linear model was used to estimate the association between maternal periconceptional folic acid or multiple micronutrients supplementation and perinatal mortality rate.Results:The overall perinatal mortality rate was 2.71‰.The perinatal mortality rates for maternal nutrients supplementation containing folic acid and no supplementation during periconceptional period were 2.63‰ and 3.43‰,respectively,and the difference in rates was not statistically significant[crude risk ratio(cRR)=0.77,95％CI:0.54-1.14].After adjusting for potential confounding factors in-cluding ethnicity,age,education level,occupation,household registration,parity,numbers of fetuses,gestational age,pregnant with assisted reproductive technology,delivery year and pre-pregnancy body mass index,the rates remained not statistically significant[adjusted risk ratio(aRR)=0.93,95％CI:0.77-1.13].The perinatal mortality rates were 2.23‰ and 2.99‰ for pure folic acid and multi-nutrients supplements containing folic acid,respectively,and the difference in rates was statistically sig-nificant(cRR=1.34,95％CI:1.02-1.76).The rates difference remained statistically significant after adjusting for potential confounders(aRR=1.31,95％CI:1.06-1.62).Additionally,the peri-natal mortality rates differences among the non-supplementation group and the supplementation group with variate timing of initiation(pre-conception or post-conception)or frequency of supplementation(low-frequency or high-frequency)were not statistically significant,regardless of adjusting for confounders.Conclusion:The overall perinatal mortality rate was lower than the national average level in Tongzhou District of Beijing.Maternal periconceptional supplementation of pure folic acid or micronutrients contai-ning folic acid had no impact on perinatal mortality.The association between maternal periconceptional supplementation of multiple micronutrients containing folic acid and perinatal mortality rate need further research.

Objective:To investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.