Objective Based on the"preventive treatment of disease"theory and real-world data,this study aimed to evaluate the clinical efficacy of Yangyin Shugan Formula in patients with ovarian dysfunction characterized by the syndrome of kidney deficiency and liver depression at different stages and to provide evidence for optimizing the timing of traditional Chinese medicine(TCM)in premature ovarian insufficiency(POI)management.Methods Ovarian dysfunction patients under 40 years old characterized by syndrome of kidney deficiency and liver depression,registered in the outpatient electronic medical records of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to December 2023,were stratified into three groups:subclinical POI,POI,and premature ovarian failure(POF)groups.The therapeutic outcomes of the three groups of patients were compared,including TCM syndrome total response rates,menstrual total response rates/normalization(cured)rates,base follicle-stimulating hormone(FSH)total response rate/normalization rates and anti-Müllerian hormone(AMH)levels.Results A total of 307 patients meeting the research criteria were included(97 cases in subclinical POI group,112 cases in POI group,and 98 cases in POF group).The TCM syndrome total response rates ranked as subclinical POI group(98.97%,96/97)>POI group(95.54%,107/112)>POF group(83.67%,82/98),with the POF group was lower than that of the subclinical POI and POI groups(P<0.017);while the difference of the subclinical POI group with the POI group was not significant.Menstrual total response rates ranked as subclinical POI group(97.22%,70/72)>POI group(72.32%,81/112)>POF group(51.02%,50/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017);normalization rates ranked as subclinical POI group(90.28%,65/72)>POI group(54.46%,61/112)>POF group(26.53%,26/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).FSH total response rates ranked as subclinical POI group(89.69%,87/97)>POI group(81.25%,91/112)>POF group(60.20%,59/98),while POF group was lower than that of the other two groups(P<0.017),and the difference of the subclinical POI group with the POI group was not significant.Normalization FSH rates ranked as subclinical POI group(71.13%,69/97)>POI group(53.57%,60/112)>POF group(16.33%,16/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).Compared with before treatment,the FSH levels in all three groups decreased after treatment(P<0.01).The reduction of FSH in the POF and POI groups were better than that in the subclinical P OI group(P<0.017).No significant difference was observed in the reduction of FSH between the POI and POF groups.Post-treatment AMH elevation observed in the subclinical POI and POI groups(P<0.01).Conclusion Yangyin Shugan Formula improves the menstrual conditions and TCM syndromes across all the stages.It also improves elevated FSH levels across all the stages and has a specific effect on normalizing FSH and menstruation.Yangyin Shugan Formula increases the AMH levels of patients with subclinical POI and POI,highlighting the applicability of TCM in staged preventive management.

Objective:To investigate the risk factors and construct a nomogram prediction model for neonatal bacterial meningitis (BM).Methods:A retrospective cohort study was conducted on 1 228 neonates who underwent lumbar puncture for cerebrospinal fluid examination in the Department of Neonatology at Gansu Provincial Women and Child Healthcare Hospital from December 2019 to February 2024. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 7∶3 using a computer program. Rank sum test or Chi-square tests were used to compare differences between the two cohorts. The subjects were divided into BM and non-BM groups based on the presence or absence of BM. Multivariate logistic regression analysis (forward stepwise regression method) was used in the training cohort to identify risk factors for BM. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess the discrimination and calibration of the model, respectively. Calibration curves were used to evaluate the accuracy of the model and to construct the nomogram. Internal validation was performed using the Bootstrap resampling method. Decision curve analysis was used to assess the clinical utility of the model. Results:Among the 1 228 neonates, 151 (12.3%) had BM. The training cohort included 859 neonates, of whom 106 (12.3%) had BM and 753 (87.7%) did not. The validation cohort included 369 neonates, of whom 45 (12.2%) had BM and 324 (87.8%) did not. The results of the multivariate logistic regression analysis in the training cohort showed that sepsis ( OR=4.446, 95% CI:2.583-7.653), convulsions ( OR=3.749, 95% CI:1.930-7.280), high maximum body temperature ( OR=2.027, 95% CI:1.636-2.513), and elevated C-reactive protein ( OR=1.007, 95% CI:1.003-1.012) were independent risk factors for BM, while greater gestational age at birth ( OR=0.946, 95% CI: 0.898-0.995) and higher hemoglobin levels ( OR=0.990, 95% CI:0.981-0.998) were protective factors for BM (all P<0.05). Based on these findings, a nomogram prediction model for neonatal BM was constructed and validated for accuracy. The AUC values of the nomogram model in the training and validation cohorts were 0.796 (95% CI: 0.750-0.843) and 0.781 (95% CI: 0.700-0.862), respectively. The Hosmer-Lemeshow goodness-of-fit test showed P>0.05 in both cohorts. The clinical decision curve analysis demonstrated good net benefit across most threshold ranges. Conclusions:Sepsis, convulsions, high maximum body temperature, and elevated C-reactive protein increase the risk of neonatal BM. The nomogram model constructed based on these factors, combined with gestational age and hemoglobin levels, provides a reference value for predicting the risk of neonatal BM.

Objective Based on the"preventive treatment of disease"theory and real-world data,this study aimed to evaluate the clinical efficacy of Yangyin Shugan Formula in patients with ovarian dysfunction characterized by the syndrome of kidney deficiency and liver depression at different stages and to provide evidence for optimizing the timing of traditional Chinese medicine(TCM)in premature ovarian insufficiency(POI)management.Methods Ovarian dysfunction patients under 40 years old characterized by syndrome of kidney deficiency and liver depression,registered in the outpatient electronic medical records of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to December 2023,were stratified into three groups:subclinical POI,POI,and premature ovarian failure(POF)groups.The therapeutic outcomes of the three groups of patients were compared,including TCM syndrome total response rates,menstrual total response rates/normalization(cured)rates,base follicle-stimulating hormone(FSH)total response rate/normalization rates and anti-Müllerian hormone(AMH)levels.Results A total of 307 patients meeting the research criteria were included(97 cases in subclinical POI group,112 cases in POI group,and 98 cases in POF group).The TCM syndrome total response rates ranked as subclinical POI group(98.97%,96/97)>POI group(95.54%,107/112)>POF group(83.67%,82/98),with the POF group was lower than that of the subclinical POI and POI groups(P<0.017);while the difference of the subclinical POI group with the POI group was not significant.Menstrual total response rates ranked as subclinical POI group(97.22%,70/72)>POI group(72.32%,81/112)>POF group(51.02%,50/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017);normalization rates ranked as subclinical POI group(90.28%,65/72)>POI group(54.46%,61/112)>POF group(26.53%,26/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).FSH total response rates ranked as subclinical POI group(89.69%,87/97)>POI group(81.25%,91/112)>POF group(60.20%,59/98),while POF group was lower than that of the other two groups(P<0.017),and the difference of the subclinical POI group with the POI group was not significant.Normalization FSH rates ranked as subclinical POI group(71.13%,69/97)>POI group(53.57%,60/112)>POF group(16.33%,16/98),the differences among the three groups and in the post-hoc comparisons were significant(P<0.01,P<0.017).Compared with before treatment,the FSH levels in all three groups decreased after treatment(P<0.01).The reduction of FSH in the POF and POI groups were better than that in the subclinical P OI group(P<0.017).No significant difference was observed in the reduction of FSH between the POI and POF groups.Post-treatment AMH elevation observed in the subclinical POI and POI groups(P<0.01).Conclusion Yangyin Shugan Formula improves the menstrual conditions and TCM syndromes across all the stages.It also improves elevated FSH levels across all the stages and has a specific effect on normalizing FSH and menstruation.Yangyin Shugan Formula increases the AMH levels of patients with subclinical POI and POI,highlighting the applicability of TCM in staged preventive management.

Objective:To investigate the risk factors and construct a nomogram prediction model for neonatal bacterial meningitis (BM).Methods:A retrospective cohort study was conducted on 1 228 neonates who underwent lumbar puncture for cerebrospinal fluid examination in the Department of Neonatology at Gansu Provincial Women and Child Healthcare Hospital from December 2019 to February 2024. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 7∶3 using a computer program. Rank sum test or Chi-square tests were used to compare differences between the two cohorts. The subjects were divided into BM and non-BM groups based on the presence or absence of BM. Multivariate logistic regression analysis (forward stepwise regression method) was used in the training cohort to identify risk factors for BM. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess the discrimination and calibration of the model, respectively. Calibration curves were used to evaluate the accuracy of the model and to construct the nomogram. Internal validation was performed using the Bootstrap resampling method. Decision curve analysis was used to assess the clinical utility of the model. Results:Among the 1 228 neonates, 151 (12.3%) had BM. The training cohort included 859 neonates, of whom 106 (12.3%) had BM and 753 (87.7%) did not. The validation cohort included 369 neonates, of whom 45 (12.2%) had BM and 324 (87.8%) did not. The results of the multivariate logistic regression analysis in the training cohort showed that sepsis ( OR=4.446, 95% CI:2.583-7.653), convulsions ( OR=3.749, 95% CI:1.930-7.280), high maximum body temperature ( OR=2.027, 95% CI:1.636-2.513), and elevated C-reactive protein ( OR=1.007, 95% CI:1.003-1.012) were independent risk factors for BM, while greater gestational age at birth ( OR=0.946, 95% CI: 0.898-0.995) and higher hemoglobin levels ( OR=0.990, 95% CI:0.981-0.998) were protective factors for BM (all P<0.05). Based on these findings, a nomogram prediction model for neonatal BM was constructed and validated for accuracy. The AUC values of the nomogram model in the training and validation cohorts were 0.796 (95% CI: 0.750-0.843) and 0.781 (95% CI: 0.700-0.862), respectively. The Hosmer-Lemeshow goodness-of-fit test showed P>0.05 in both cohorts. The clinical decision curve analysis demonstrated good net benefit across most threshold ranges. Conclusions:Sepsis, convulsions, high maximum body temperature, and elevated C-reactive protein increase the risk of neonatal BM. The nomogram model constructed based on these factors, combined with gestational age and hemoglobin levels, provides a reference value for predicting the risk of neonatal BM.

ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine（TCM） through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects， they were divided into the "1-2 seven" group （under 21 years old）， "3 seven" group （21-27 years old）， "4 seven" group （28-34 years old）， "5 seven" group （35-41 years old）， "6 seven" group （42-48 years old） and "7 seven" and older group （49 years old and above）. The age， average menstrual cycle in the past 3 months， basic hormone levels including follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， testosterone （T） and FSH/LH value， and anti-müllerian hormone （AMH） levels were collected and compared. ResultsA total of 1221 cases were included. The differences in FSH， LH， FSH/LH values， E₂， T， AMH levels and average menstrual cycle among the groups were statistically significant （P＜0.05 or P＜0.01）. AMH peaked in the "3 seven" group. Compared to those in the "3 seven" group， the FSH/LH value in the "4 seven" group increased， while the LH， AMH and T levels decreased， and the menstrual cycle was shortened （P＜0.01）. The FSH/LH， LH， AMH， T and menstrual cycle in the "5 seven" group were consistent with the changing trend of those in the "4 seven" group， while the FSH and E₂ levels in the "5 seven" group were significantly higher （P＜0.05 or P＜0.01）. Compared to those in the "5 seven" group， the FSH， LH and E₂ levels of the "6 seven" group increased， and the AMH and T levels continued to decrease （P＜0.05 or P＜0.01）. Compared to those in the "6 seven" group， the FSH and LH levels of the "7 seven" and older group continued to increase， and the AMH and E₂ levels decreased （P＜0.01）. ConclusionThe law of women reproductive aging in the "seven-year period" theory is basically consistent with the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. The reproductive capacity reaches its peak in the "three-seven-year period" and gradually moves towards reproductive aging in the "four-seven-year period".

Objective Based on the real-world data,we aimed to study the clinical efficacy and safety of Yangyin Shugan(method of nourishing yin and soothing liver)Decoction,an empirical prescription of famous traditional Chinese medicine(TCM)practitioners,in the treatment of premature ovarian insufficiency(POI)with pattern of kidney deficiency and liver depression.Methods A total of 618 POI patients with pattern of kidney deficiency and liver depression who registered in the outpatient electronic medical record system of Guangdong Provincial Hospital of Chinese Medicine were collected from January 2020 to December 2023.After 1:1 propensity matching,a total of 222 patients with POI who met the criteria were included and assigned to a Yangyin Shugan Decoction group(treated with Yangyin Shugan Decoction only)and a hormone control group(hormone treatment only),with 111 cases in each group.Age,age at menarche,marriage status,duration,times of pregnancy,times of miscarriage,menstrual total score,total score of TCM syndrome,basal serum follicle-stimulating hormone(bFSH),and anti-Müllerian hormone(AMH)were recorded and compared.After 3 to 4 months of treatment,the clinical efficacy between the two groups include TCM syndromes,menstrual,bFSH,and menstrual normalization rates during the follow-up period(3 months after discontinuation of medication)were compared.Additionally,comparisons were also made before and after treatment for the total score of TCM syndrome and scores of individual symptom,menstrual total score and scores of indicator,bFSH level,and AMH levels in both groups.Results(ⅰ)The total effective rate of the TCM syndrome in the Yangyin Shugan Decoction group and hormone control group were 85.59%and 52.25%,respectively;the total effective rate of menstrual were 54.95%and 90.99%,respectively;the menstrual normalization rate during the follow-up period were 31.53%and 9.01%,respectively;and regarding bFSH efficacy,the total effective rate were 70.27%and 27.03%,respectively,and the normalization rate of bFSH were 35.14%and 9.01%,respectively.The differences between the two groups were statistically significant(P<0.01).(ⅱ)The bFSH value in the Yangyin Shugan Decoction group decreased after treatment compared to before treatment(P<0.01),while the bFSH value in the hormone control group showed no change before and after treatment.The AMH value increased after treatment compared to before treatment in Yangyin Shugan Decoction group(P<0.01),while the AMH value in the hormone control group showed no change before and after treatment.The difference of bFSH and AMH between the two groups after treatment was statistically significant(P<0.01).(ⅲ)After treatment,the total score of TCM syndrome and the scores of individual symptom in the Yangyin Shugan Decoction group were lower than those before treatment(P<0.01);the total score of TCM syndrome,scores of hot flushes and sweating,hyposexuality,and insomnia in the hormone control group were lower than those before treatment(P<0.01).After treatment,the total score of TCM syndrome and the scores of individual symptom in the Yangyin Shugan Decoction group were lower than those in the hormone control group(P<0.01).(ⅳ)After treatment,the menstrual total score,scores of menstrual cycle,period,menstrual flow,and menstrual blood color in the Yangyin Shugan Decoction group were lower than those before treatment(P<0.01);the menstrual total score,score of menstrual cycle,period,and menstrual flow in the hormone control group were lower than those before treatment(P<0.01);after treatment,the menstrual total score and menstrual cycle score in the hormone control group were better than those in the Yangyin Shugan Decoction group(P<0.01).(ⅴ)No adverse reactions were observed in the Yangyin Shugan Decoction group and 29 cases of adverse reactions were observed in the hormone control group.Conclusion Yangyin Shugan Decoction can effectively improve TCM syndrome in POI patients with pattern of kidney deficiency and liver depression;downregulate the elevated bFSH level,increase the low AMH level,and effectively improve ovarian function,even continue to maintain menstruation after drug withdrawal.In the real world,Yangyin Shugan Decoction got satisfactory efficacy and good safety in the treatment of POI,which deserves clinical promotion and application.

In recent years, traditional Chinese medicine (TCM) has made great progress in the prevention and treatment of cancer. It has gradually revealed its characteristics and advantages in clinical practice, including alleviating clinical symptoms, prolonging survival time, decreasing the adverse effects of chemotherapy, and improving living quality. However, clinical TCM treatment of cancer lacks systematic theoretical guidance, because ancient TCM has not formed a recognized theoretical system of cognitive cancer, and there still are different opinions on the pathogenesis of cancer. Due to the complexity of cancer, the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors, such as pathogenic wind, cold, dampness, summer heat, dryness, and fire. Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin. In the 1990s, the thought of cancerous toxin was first proposed by Prof Zhou Zhongying, a TCM master based on more than 60 years of clinical practice, who used “pandemic Qi (Li-Qi) is a specific pathogenic factor of epidemic disease” in Wenyi Lun (Treatise on Pestilence) for references. The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin. It holds that the cancerous toxin, a special pathogenic factor of cancer, is the key pathogenesis of the occurrence of malignant tumors. According to the pathogenesis theory of cancerous toxin, the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin, and the deficiency of the vital Qi (Zheng-Qi). Therefore, the treatment principle involves eliminating pathogenic factors, resolving cancerous toxin, and supporting the vital Qi. The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward. System theory has much in common with the concepts in the theory system of TCM, such as the universal relation theory, asking for a concrete analysis of concrete conditions, the humanism thought, and so on. This article aims to describe, review, and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.

Objective Based on the real-world data,we aimed to study the clinical efficacy and safety of Yangyin Shugan(method of nourishing yin and soothing liver)Decoction,an empirical prescription of famous traditional Chinese medicine(TCM)practitioners,in the treatment of premature ovarian insufficiency(POI)with pattern of kidney deficiency and liver depression.Methods A total of 618 POI patients with pattern of kidney deficiency and liver depression who registered in the outpatient electronic medical record system of Guangdong Provincial Hospital of Chinese Medicine were collected from January 2020 to December 2023.After 1:1 propensity matching,a total of 222 patients with POI who met the criteria were included and assigned to a Yangyin Shugan Decoction group(treated with Yangyin Shugan Decoction only)and a hormone control group(hormone treatment only),with 111 cases in each group.Age,age at menarche,marriage status,duration,times of pregnancy,times of miscarriage,menstrual total score,total score of TCM syndrome,basal serum follicle-stimulating hormone(bFSH),and anti-Müllerian hormone(AMH)were recorded and compared.After 3 to 4 months of treatment,the clinical efficacy between the two groups include TCM syndromes,menstrual,bFSH,and menstrual normalization rates during the follow-up period(3 months after discontinuation of medication)were compared.Additionally,comparisons were also made before and after treatment for the total score of TCM syndrome and scores of individual symptom,menstrual total score and scores of indicator,bFSH level,and AMH levels in both groups.Results(ⅰ)The total effective rate of the TCM syndrome in the Yangyin Shugan Decoction group and hormone control group were 85.59%and 52.25%,respectively;the total effective rate of menstrual were 54.95%and 90.99%,respectively;the menstrual normalization rate during the follow-up period were 31.53%and 9.01%,respectively;and regarding bFSH efficacy,the total effective rate were 70.27%and 27.03%,respectively,and the normalization rate of bFSH were 35.14%and 9.01%,respectively.The differences between the two groups were statistically significant(P<0.01).(ⅱ)The bFSH value in the Yangyin Shugan Decoction group decreased after treatment compared to before treatment(P<0.01),while the bFSH value in the hormone control group showed no change before and after treatment.The AMH value increased after treatment compared to before treatment in Yangyin Shugan Decoction group(P<0.01),while the AMH value in the hormone control group showed no change before and after treatment.The difference of bFSH and AMH between the two groups after treatment was statistically significant(P<0.01).(ⅲ)After treatment,the total score of TCM syndrome and the scores of individual symptom in the Yangyin Shugan Decoction group were lower than those before treatment(P<0.01);the total score of TCM syndrome,scores of hot flushes and sweating,hyposexuality,and insomnia in the hormone control group were lower than those before treatment(P<0.01).After treatment,the total score of TCM syndrome and the scores of individual symptom in the Yangyin Shugan Decoction group were lower than those in the hormone control group(P<0.01).(ⅳ)After treatment,the menstrual total score,scores of menstrual cycle,period,menstrual flow,and menstrual blood color in the Yangyin Shugan Decoction group were lower than those before treatment(P<0.01);the menstrual total score,score of menstrual cycle,period,and menstrual flow in the hormone control group were lower than those before treatment(P<0.01);after treatment,the menstrual total score and menstrual cycle score in the hormone control group were better than those in the Yangyin Shugan Decoction group(P<0.01).(ⅴ)No adverse reactions were observed in the Yangyin Shugan Decoction group and 29 cases of adverse reactions were observed in the hormone control group.Conclusion Yangyin Shugan Decoction can effectively improve TCM syndrome in POI patients with pattern of kidney deficiency and liver depression;downregulate the elevated bFSH level,increase the low AMH level,and effectively improve ovarian function,even continue to maintain menstruation after drug withdrawal.In the real world,Yangyin Shugan Decoction got satisfactory efficacy and good safety in the treatment of POI,which deserves clinical promotion and application.

Objective: The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin. Methods: Linarin solid dispersion (LSD) and linarin liposome (LL) were developed via the solvent method and the thin film hydration method respectively. The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug. The pharmacokinetics of linarin, LSD and LL in rats after ig administration were carried out by high performance liquid chromatography (HPLC) method. Results: The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin. The permeation coefficients of LSD and LL were greater than 10

Objective To investigate the effect of rh-resistin on lipid metabolism in HepG2 cells and to elucidate its relation to AMPK pathway. Methods We treated the HepG2 cells with 50 ng/ml rh-resistin and 0.5 mmol/L palmitic acid,used siRNA technique to inhibite α2 subunite expression of AMPK in HepG2 cells and quantitative RT-PCR to detect ACC1,ACC2,and HL mRNA expression levels of related lipid metabolism genes. The P-AMPK-Thr172 of AMPK and P-ACC-Ser79 of ACC were determined by Western blotting. The Lipid accumu-lation in cells was determined by images of Laser Scanning Confocal Microscope after Nile red staining. Results Rh-resistin decreased the AMPKα2,HL mRNA expressions and the phosphorylation level of AMPK and ACC in both basal and insulin-stimulated conditions (P < 0.05),had no influence on ACC2 mRNA expressions (P >0.05),while it increased ACC2 mRNA expressions and cytoplasmic lipid droplets in the same conditions (P <0.05). Conclusion Rh-resistin may affect lipid metabolism via AMPK pathway with increase of fatty acid synthe-sis and inhibition of triglyceride catabolism,which leading to lipid accumulation in HepG2 cells.