ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

Objective To investigate the clinical efficacy of Jiawei Tai Yuan Yin combined with allylestradiol tablets for the treatment of early threatened abortion complicated by subchorionic hematoma(SCH).Methods A total of 120 patients with early threatened miscarriage combined with SCH were selected and divided into the observation group(Jiawei Tai Yuan Yin+allylestradiol tablets,60 cases)and the control group(allylestradiol tablets,60 cases)according to the treatment regimen.Seven days was one course of treatment,and both groups of patients were treated for two courses.Changes of traditional Chinese medicine(TCM)syndrome score before treatment and 14 days after treatment,clinical efficacy,SCH area,the ratio of SCH area to gestational sac area,vaginal bleeding(duration and volume),the miscarriage rate in the early stage of pregnancy,the ratio of auxiliary T cells to inhibitory T cells(Th/Ts)and the level of carbohydrate antigen 125(CA125)were observed.Results After 14 days of treatment,TCM syndrome scores,SCH area,the ratio of SCH area to gestational sac area,the Th/Ts ratio and the CA125 level were decreased in the two groups,and those of the observation group were lower than those of the control group(P＜0.05).After 14 days of treatment,the total effective rate was higher in the observation group than that of the control group(P＜0.05).During the treatment period,the duration of vaginal bleeding,the amount of vaginal bleeding and the miscarriage rate in the early stage of pregnancy were lower in the observation group than those in the control group(P＜0.05).Conclusion The combination of Jiawei Tai Yuan Yin and allylestradiol tablets can effectively treat early threatened miscarriage with SCH,thereby reducing the miscarriage rate in early pregnancy.

Objective:To establish and validate a nomogram for postoperative disease progression (including recurrence, metastasis, and death) in patients with primary liver cancer (PLC) based on quantitative CT measurements of relevant indicators.Methods:Clinical data of 290 patients with PLC admitted to Zhongshan Hospital Affiliated to Fudan University and Kunshan Hospital Affiliated to Jiangsu University from January 2016 to December 2021 were retrospectively collected, including 177 males and 113 females, aged (60.3±11.9) years. Two hundred and three patients admitted to Zhongshan Hospital Affiliated to Fudan University were used as the training set, and 87 patients admitted to Kunshan Hospital Affiliated to Jiangsu University were used as the validation set. The patient's condition of ascites , tumor length, number of lesions, tumor differentiation degree, relevant indicators of quantitative CT detection (including decreased muscle mass and increased intra-abdominal fat area), prognosis and other clinical data were recorded. The influencing factors of postoperative disease progression was analyzed through multiple logistic regression in the training set, and the nomogram model was constructed based on the results of multiple factor analysis. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves and calibration curves. The clinical applicability of predictive models was evaluated using the decision curve analysis.Results:The results of multiple logistic regression analysis showed that the increase in maximum tumor diameter ( OR=1.519, 95% CI: 1.251-1.843), multiple lesions ( OR=3.193, 95% CI: 1.493-6.830), low tumor differentiation ( OR=5.604, 95% CI: 2.442-12.863), ascites ( OR=3.321, 95% CI: 1.166-9.463), portal vein tumor thrombus ( OR=3.990, 95% CI: 1.681-9.474), decreased muscle mass ( OR=2.173, 95% CI: 1.051-4.492) and increased intra-abdominal fat area ( OR=2.634, 95% CI: 1.276-5.438) were independent risk factors for postoperative disease progression in patients with PLC (all P<0.05). A nomogram was constructed based on the above variables, and the area under the ROC curve for predicting postoperative disease progression in patients with PLC in the training set and validation set was 0.862 (95% CI: 0.810-0.914) and 0.879 (95% CI: 0.806-0.953), respectively. The calibration curve and ideal curve fit well, indicating that the predicted situation was basically consistent with the actual situation. Decision curve analysis showed that the column chart model had a high clinical net benefit and good clinical prediction effectiveness. Conclusion:The nomogram constructed based on the maximum diameter of the tumor, the number of lesions, the degree of tumor differentiation, ascites, portal vein tumor thrombus, decreased muscle mass, and increased intra-abdominal fat area has good predictive power for postoperative disease progression in patients with PLC.

Objective To explore the clinical characteristics and risk factors of upper urinary tract stones complicated with non-alcoholic fatty liver disease(NAFLD),so as to provide reference for the prevention of this disease.Methods The clinical data of 158 NAFLD patients undergoing surgical treatment in our hospital during Jan.2022 and Jul.2023 were retrospectively analyzed.According to whether the patients were complicated with NAFLD,they were divided into the NAFLD group(n=56)and non-NAFLD group(n=102).The general data,laboratory indexes and 24-h urinary metabolic indexes were compared between the two groups,and the risk factors were analyzed with univariate and multivariate logistic regression analyses.Results Compared with the non NAFLD group,the NAFLD group had higher BMI[(28.17±4.17)vs.(24.11±3.72),P＜0.001],blood uric acid[(354.13±111.01)μmol/L vs.(294.41±93.72)μmol/L,P＜0.001],and 24-h urinary oxalate level[(37.74±15.00)mmol vs.(27.73±15.27)mmol,P＜0.001].Multivariate logistic analysis showed that BMI(OR=1.311,P＜0.001),24-h urinary oxalate(OR=1.046,P=0.004),and 24-h urinary magnesium(OR=0.599,P=0.002)were the independent factors for NAFLD with upper urinary tract stones.Conclusion NAFLD complicated with upper urinary tract stones is significantly associated with high BMI,high 24-h urinary oxalate,and low 24-h urinary magnesium.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective To investigate the clinical efficacy of Jiawei Tai Yuan Yin combined with allylestradiol tablets for the treatment of early threatened abortion complicated by subchorionic hematoma(SCH).Methods A total of 120 patients with early threatened miscarriage combined with SCH were selected and divided into the observation group(Jiawei Tai Yuan Yin+allylestradiol tablets,60 cases)and the control group(allylestradiol tablets,60 cases)according to the treatment regimen.Seven days was one course of treatment,and both groups of patients were treated for two courses.Changes of traditional Chinese medicine(TCM)syndrome score before treatment and 14 days after treatment,clinical efficacy,SCH area,the ratio of SCH area to gestational sac area,vaginal bleeding(duration and volume),the miscarriage rate in the early stage of pregnancy,the ratio of auxiliary T cells to inhibitory T cells(Th/Ts)and the level of carbohydrate antigen 125(CA125)were observed.Results After 14 days of treatment,TCM syndrome scores,SCH area,the ratio of SCH area to gestational sac area,the Th/Ts ratio and the CA125 level were decreased in the two groups,and those of the observation group were lower than those of the control group(P＜0.05).After 14 days of treatment,the total effective rate was higher in the observation group than that of the control group(P＜0.05).During the treatment period,the duration of vaginal bleeding,the amount of vaginal bleeding and the miscarriage rate in the early stage of pregnancy were lower in the observation group than those in the control group(P＜0.05).Conclusion The combination of Jiawei Tai Yuan Yin and allylestradiol tablets can effectively treat early threatened miscarriage with SCH,thereby reducing the miscarriage rate in early pregnancy.

Objective To explore the clinical characteristics and risk factors of upper urinary tract stones complicated with non-alcoholic fatty liver disease(NAFLD),so as to provide reference for the prevention of this disease.Methods The clinical data of 158 NAFLD patients undergoing surgical treatment in our hospital during Jan.2022 and Jul.2023 were retrospectively analyzed.According to whether the patients were complicated with NAFLD,they were divided into the NAFLD group(n=56)and non-NAFLD group(n=102).The general data,laboratory indexes and 24-h urinary metabolic indexes were compared between the two groups,and the risk factors were analyzed with univariate and multivariate logistic regression analyses.Results Compared with the non NAFLD group,the NAFLD group had higher BMI[(28.17±4.17)vs.(24.11±3.72),P＜0.001],blood uric acid[(354.13±111.01)μmol/L vs.(294.41±93.72)μmol/L,P＜0.001],and 24-h urinary oxalate level[(37.74±15.00)mmol vs.(27.73±15.27)mmol,P＜0.001].Multivariate logistic analysis showed that BMI(OR=1.311,P＜0.001),24-h urinary oxalate(OR=1.046,P=0.004),and 24-h urinary magnesium(OR=0.599,P=0.002)were the independent factors for NAFLD with upper urinary tract stones.Conclusion NAFLD complicated with upper urinary tract stones is significantly associated with high BMI,high 24-h urinary oxalate,and low 24-h urinary magnesium.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective:To establish and validate a nomogram for postoperative disease progression (including recurrence, metastasis, and death) in patients with primary liver cancer (PLC) based on quantitative CT measurements of relevant indicators.Methods:Clinical data of 290 patients with PLC admitted to Zhongshan Hospital Affiliated to Fudan University and Kunshan Hospital Affiliated to Jiangsu University from January 2016 to December 2021 were retrospectively collected, including 177 males and 113 females, aged (60.3±11.9) years. Two hundred and three patients admitted to Zhongshan Hospital Affiliated to Fudan University were used as the training set, and 87 patients admitted to Kunshan Hospital Affiliated to Jiangsu University were used as the validation set. The patient's condition of ascites , tumor length, number of lesions, tumor differentiation degree, relevant indicators of quantitative CT detection (including decreased muscle mass and increased intra-abdominal fat area), prognosis and other clinical data were recorded. The influencing factors of postoperative disease progression was analyzed through multiple logistic regression in the training set, and the nomogram model was constructed based on the results of multiple factor analysis. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves and calibration curves. The clinical applicability of predictive models was evaluated using the decision curve analysis.Results:The results of multiple logistic regression analysis showed that the increase in maximum tumor diameter ( OR=1.519, 95% CI: 1.251-1.843), multiple lesions ( OR=3.193, 95% CI: 1.493-6.830), low tumor differentiation ( OR=5.604, 95% CI: 2.442-12.863), ascites ( OR=3.321, 95% CI: 1.166-9.463), portal vein tumor thrombus ( OR=3.990, 95% CI: 1.681-9.474), decreased muscle mass ( OR=2.173, 95% CI: 1.051-4.492) and increased intra-abdominal fat area ( OR=2.634, 95% CI: 1.276-5.438) were independent risk factors for postoperative disease progression in patients with PLC (all P<0.05). A nomogram was constructed based on the above variables, and the area under the ROC curve for predicting postoperative disease progression in patients with PLC in the training set and validation set was 0.862 (95% CI: 0.810-0.914) and 0.879 (95% CI: 0.806-0.953), respectively. The calibration curve and ideal curve fit well, indicating that the predicted situation was basically consistent with the actual situation. Decision curve analysis showed that the column chart model had a high clinical net benefit and good clinical prediction effectiveness. Conclusion:The nomogram constructed based on the maximum diameter of the tumor, the number of lesions, the degree of tumor differentiation, ascites, portal vein tumor thrombus, decreased muscle mass, and increased intra-abdominal fat area has good predictive power for postoperative disease progression in patients with PLC.