ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis （KOA） using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS）， network pharmacology， and molecular docking technology. MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE， validated through the Gene Expression Omnibus （GEO） database， and molecular docking was performed between key active ingredients and core targets. ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes， respectively， with 410 components in total after de-duplication， mainly including flavonoids， coumarins， terpenoids， organic acids， and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration"， "cell growth and death"， "immune system"， and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients， such as bletillin A， formononetin， morin， oxymatrine， aconitine， gallic acid， curdione， apigenin， naringenin， and oleanolic acid， tightly bound to functional domains of 10 key targets including Jun proteins（JUN）， interleukin-6 （IL-6）， protein kinase B1 （Akt1）， Caspase-3， nuclear transcription factor-κB subunit p65（RELA）， nuclear factor-kappaB1（NF-κB1）， Cyclin D₁， mammalian target of rapamycin（mTOR）， tumor necrosis factor （TNF）， and Fos proto-oncogene protein （FOS）. These interactions synergistically regulated the phosphatidylinositol 3-kinase （PI3K）/Akt/mTOR-related signaling axis and nervous system-related pathways， mediating cartilage repair， reducing inflammation and pain， and improving KOA. ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways， providing a reference for subsequent exploration of its substance benchmark and mechanism of action.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

Objective:To analyze the epidemic trend of influenza-like illness（ILI）cases，etiological detection results，and the evolution of the hemagglutinin（HA）gene of the predominant strains in Hanzhong City，Shaanxi Province during the 2018-2024 influenza seasons.Methods:ILI sentinel surveillance data and network laboratory test results during the 2018-2024 influenza seasons in Hanzhong City，Shaanxi Province were collected for descriptive analysis. The HA gene sequences of 25 predominant strains were obtained through whole-genome deep sequencing method，and then compared with the vaccine strains recommended by the World Health Organization in the same period to analyze the evolution of the virus.Results:A total of 37 770 cases of ILI were reported in Hanzhong City during the 2018-2024 influenza seasons，and the proportion of total ILI cases（ILI%）was 2.87%（37 770/1 316 009）. The epidemic trend of ILI showed an obvious epidemic peak in winter and spring（from December of the current year to March of the following year）. The specimens with the highest positive rate were of type A（H3N2）（39.12%，365/933），and the predominant epidemic strains in each influenza season alternated among A（H1N1）pdm09（in the 2018-2019 and 2022-2023 influenza seasons），A（H3N2）（in the 2019-2020 and 2023-2024 influenza seasons）and B（Victoria）（in the 2021-2022 influenza season）. The phylogenetic relationship gradually became more distant over time across different influenza seasons. Among them，the epidemic strains of A（H1N1）pdm09 belonged to the 6B.1 clade，and the evolution mainly occurred in the Sa and Sb regions of the HA epitope. Meanwhile，the epidemic strains of A（H3N2）belonged to the 3C clade，and the evolution mainly took place in the A，B and C regions of the HA epitope. The strains of the B（Victoria）lineage belonged to the V1a.3a.2 clade，and the evolution mainly occurred in the 120-loop，150-loop，and 190-helix regions of the HA epitope.Conclusions:The influenza epidemic in Hanzhong City has obvious seasonality，and the amino acids of the epidemic strains have shown a certain degree of variation over the years. In future prevention and control work，influenza surveillance should be continuously strengthened，and the change trend of the predominant circulating strains should be closely monitored.

Objective:To analyze the epidemic trend of influenza-like illness（ILI）cases，etiological detection results，and the evolution of the hemagglutinin（HA）gene of the predominant strains in Hanzhong City，Shaanxi Province during the 2018-2024 influenza seasons.Methods:ILI sentinel surveillance data and network laboratory test results during the 2018-2024 influenza seasons in Hanzhong City，Shaanxi Province were collected for descriptive analysis. The HA gene sequences of 25 predominant strains were obtained through whole-genome deep sequencing method，and then compared with the vaccine strains recommended by the World Health Organization in the same period to analyze the evolution of the virus.Results:A total of 37 770 cases of ILI were reported in Hanzhong City during the 2018-2024 influenza seasons，and the proportion of total ILI cases（ILI%）was 2.87%（37 770/1 316 009）. The epidemic trend of ILI showed an obvious epidemic peak in winter and spring（from December of the current year to March of the following year）. The specimens with the highest positive rate were of type A（H3N2）（39.12%，365/933），and the predominant epidemic strains in each influenza season alternated among A（H1N1）pdm09（in the 2018-2019 and 2022-2023 influenza seasons），A（H3N2）（in the 2019-2020 and 2023-2024 influenza seasons）and B（Victoria）（in the 2021-2022 influenza season）. The phylogenetic relationship gradually became more distant over time across different influenza seasons. Among them，the epidemic strains of A（H1N1）pdm09 belonged to the 6B.1 clade，and the evolution mainly occurred in the Sa and Sb regions of the HA epitope. Meanwhile，the epidemic strains of A（H3N2）belonged to the 3C clade，and the evolution mainly took place in the A，B and C regions of the HA epitope. The strains of the B（Victoria）lineage belonged to the V1a.3a.2 clade，and the evolution mainly occurred in the 120-loop，150-loop，and 190-helix regions of the HA epitope.Conclusions:The influenza epidemic in Hanzhong City has obvious seasonality，and the amino acids of the epidemic strains have shown a certain degree of variation over the years. In future prevention and control work，influenza surveillance should be continuously strengthened，and the change trend of the predominant circulating strains should be closely monitored.

Objective To investigate the effect of triptolide(TPL)on renal interstitial fibrosis in mice with unilateral ureteral obstruction(UUO)and its mechanism.Methods Six male C57BL/6J mice were randomly selected as the sham group,and 12 mice with UUO modeling were randomly divided into the model group(UUO)and the triptolide group(TPL).Changes in serum creatinine(SCr),blood urea nitrogen(BUN),and body weight were compared among the groups.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.Immunohistochemistry staining was performed to observe the expression of α-smooth muscle actin(α-SMA)and fibronectin(Fn)in kidney tissues.Western blotting analysis was used to detect the protein expression levels of nucleotide combined with structure of oligomerization domain receptor protein 3(NLRP3),GSDMD,cGSDMD,IL-1β and IL-18.Results At week 1,the body weight of mice in the UUO and TPL groups significantly decreased compared with that in the sham group(P＜0.05).Body weight reduced in the TPL group compared with that in the Sham group at week 2(P＜0.01).There was no significant difference in body weight between the TPL and UUO groups.BUN levels did not differ significantly between the three groups.Compared with the sham group,the SCr level in the UUO group significantly increased[(15.680±1.508)μmol/L](P＜0.01).A reduction in SCr level was observed following TPL administration[(12.550±3.004)μmol/L](P＜0.05).HE staining showed that the renal tubules of mice in the UUO group were significantly dilated and atrophic,with interstitial edema and increased inflammatory cell infiltration,while the pathological damage of renal tissues was significantly alleviated after TPL treatment.Masson staining revealed that interstitial collagen deposition significantly increased in the UUO group(36.350±5.183)％(P＜0.01)and reduced after TPL administration(20.820±3.290)％(P＜0.01).Immunohistochemistry results demonstrated that the IOD levels of α-SMA(1.233±0.045)and Fn(1.337±0.045)were higher in UUO group mice than in the sham group,while the IOD levels of α-SMA(1.047±0.025)and Fn(1.113±0.021)were lower in the TPL group than in the UUO group(P＜0.05).Western blotting analysis indicated that the expression levels of NLRP3,cGSDMD,IL-1β and IL-18 in the UUO group mice were higher than those in the sham group,while the protein expression levels of the above-mentioned indicators significantly decreased after TPL treatment(P＜0.05).Conclusion TPL ameliorates renal interstitial fibrosis in mice with UUO by inhibiting NLRP3-mediated pyroptosis.

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

Objective To investigate the effect of triptolide(TPL)on renal interstitial fibrosis in mice with unilateral ureteral obstruction(UUO)and its mechanism.Methods Six male C57BL/6J mice were randomly selected as the sham group,and 12 mice with UUO modeling were randomly divided into the model group(UUO)and the triptolide group(TPL).Changes in serum creatinine(SCr),blood urea nitrogen(BUN),and body weight were compared among the groups.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.Immunohistochemistry staining was performed to observe the expression of α-smooth muscle actin(α-SMA)and fibronectin(Fn)in kidney tissues.Western blotting analysis was used to detect the protein expression levels of nucleotide combined with structure of oligomerization domain receptor protein 3(NLRP3),GSDMD,cGSDMD,IL-1β and IL-18.Results At week 1,the body weight of mice in the UUO and TPL groups significantly decreased compared with that in the sham group(P＜0.05).Body weight reduced in the TPL group compared with that in the Sham group at week 2(P＜0.01).There was no significant difference in body weight between the TPL and UUO groups.BUN levels did not differ significantly between the three groups.Compared with the sham group,the SCr level in the UUO group significantly increased[(15.680±1.508)μmol/L](P＜0.01).A reduction in SCr level was observed following TPL administration[(12.550±3.004)μmol/L](P＜0.05).HE staining showed that the renal tubules of mice in the UUO group were significantly dilated and atrophic,with interstitial edema and increased inflammatory cell infiltration,while the pathological damage of renal tissues was significantly alleviated after TPL treatment.Masson staining revealed that interstitial collagen deposition significantly increased in the UUO group(36.350±5.183)％(P＜0.01)and reduced after TPL administration(20.820±3.290)％(P＜0.01).Immunohistochemistry results demonstrated that the IOD levels of α-SMA(1.233±0.045)and Fn(1.337±0.045)were higher in UUO group mice than in the sham group,while the IOD levels of α-SMA(1.047±0.025)and Fn(1.113±0.021)were lower in the TPL group than in the UUO group(P＜0.05).Western blotting analysis indicated that the expression levels of NLRP3,cGSDMD,IL-1β and IL-18 in the UUO group mice were higher than those in the sham group,while the protein expression levels of the above-mentioned indicators significantly decreased after TPL treatment(P＜0.05).Conclusion TPL ameliorates renal interstitial fibrosis in mice with UUO by inhibiting NLRP3-mediated pyroptosis.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

Objective To explore the effect of bone marrow injury by simulating the radiation from solar particle events in order to address the radiation limit and assess risks during manned deep space exploration.Methods In line with solar particle events(the main component was protons),BALB/c mice(48 mice per group)were irradiated with 90 MeV protons at the doses of 0,0.1,0.3,0.5,1 and 2 Gy.At 3 and 7 days after irradiation.Routine blood counters were employed to detect peripheral blood changes,Giemsa staining was used to detect the ratio of granulocytes to erythrocytes in bone marrow,and flow cytometry was adopted to detect the proportion of bone marrow stem cells,cell subsets and apoptosis before the dose-response relationship and threshold were analyzed.Results In the dose range of 0.1 to 2 Gy,the number of peripheral blood white blood cells and lymphocytes decreased at 3 and 7 days after irradiation and the ratio of granulocytes to erythrocytes in bone marrow and bone marrow cell subsets were abnormal as the dose increased.Seven days after irradiation,the platelet count decreased.The minimum dose that caused significant changes was 0.5 Gy,13 models with dose-response relationships were obtained,and the minimum values of ED25,ED50 and ED63 were 0.25,0.58 and 0.76 Gy,respectively.Conclusion A total of 13 dose-response relationship models of proton-induced bone marrow injury in mice have been obtained,and the dose threshold of proton-induced bone marrow injury ranges from 0.25 to 0.76 Gy.