Guishenwan （GSW）， originating from Jingyue Quanshu （Zhang Jingyue's Complete Works）， is a classic traditional Chinese medicine （TCM） formula with a history of over 400 years. Designed for kidney essence deficiency syndrome， it is clinically applied to treat diseases associated with essence-blood deficiency， such as ovarian insufficiency diseases in women， oligospermia-induced infertility in men， and lumbar disc herniation. Numerous studies have confirmed its significant efficacy and advantages in managing ovarian insufficiency diseases， including diminished ovarian reserve （DOR）， premature ovarian insufficiency （POI）， and premature ovarian failure （POF）. According to recent literature， the therapeutic mechanisms of GSW in treating ovarian insufficiency diseases involve regulating the hypothalamic-pituitary-ovarian axis （HPOA） function， ameliorating reproductive endocrine disorders， improving ovarian function， modulating relevant signaling pathways， and exerting immunoregulatory and anti-inflammatory effects. A review of GSW in clinical treatment revealed that clinical applications of GSW， particularly in combination with Western medicine， not only alleviate symptoms but also compensate for the limitations of hormone replacement therapy， thereby reducing recurrence， minimizing adverse reactions， and enhancing safety. This review aims to provide a scientific basis for the rational clinical use of GSW in ovarian insufficiency diseases， offer innovative TCM strategies for developing novel ovarian-protective drugs， promote the integration of TCM and Western medicine in reproductive medicine， and ultimately contribute a Chinese approach to global management of ovarian insufficiency diseases.

ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Dry eye （DE） is a prevalent multifactorial disease of the ocular surface， clinically characterized by tear film homeostasis imbalance accompanied by related ocular surface symptoms. Specifically， the tear film is a thin liquid layer of tears covering the cornea and conjunctiva through blinking， while tear film homeostasis serves as the foundation for maintaining normal ocular surface structure and function. Insufficient tear secretion and excessive tear film evaporation lead to tear hyperosmolarity and the production of inflammatory mediators， disrupting tear film homeostasis and subsequently forming DE. Additionally， cascade reactions are triggered， resulting in a "vicious cycle of DE" that exacerbates the disease severity and prolongs its duration. Therefore， for DE treatment， it is crucial to restore tear film homeostasis and terminate this vicious cycle. Traditional Chinese medicine （TCM）， which differentiates and treats DE based on systemic conditions， often achieves favorable therapeutic outcomes， offering additional treatment options for DE. Studies have demonstrated that TCM can alleviate DE by regulating tear film homeostasis and terminating the vicious cycle. This review systematically summarizes recent basic experimental research in China and abroad on TCM in alleviating DE by regulating tear film homeostasis， aiming to provide a theoretical basis for clinical treatment and an insight for research design.

ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

Objective To evaluate the cost-effectiveness of the combination therapy of ribociclib plus fulvestrant compared to fulvestrant monotherapy as a second-line treatment for postmenopausal patients with hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-)advanced metastatic breast cancer from the perspective of the Chinese healthcare system.Methods A partitioned survival model was constructed based on MONALEESA-3 study data,with the model cycle of 4 weeks and the time range of 15 years.Total cost,quality-adjusted life years(QALYs)and incremental cost-effectiveness ratio(ICER)were compared between ribociclib combined with fulvestrant and fulvestrant monotherapy as a second-line treatment for postmenopausal patients with HR+/HER2-advanced metastatic breast cancer.The robustness of the models was validated through one-way sensitivity analysis and probabilistic sensitivity analysis.Results Compared with the fulvestrant monotherapy regimen,the ICER for the ribociclib combined with fulvestrant regimen was 187,958.06 yuan/QALY,which was below the willingness-to-pay(WTP)threshold of three times China's per capita gross domestic product(GDP)in 2024(287,247 yuan/QALY).The one-way sensitivity analysis revealed that the ICER was primarily influenced by the proportion of patients receiving subsequent treatments with the combination therapy or fulvestrant monotherapy,and the utility value of progression-free survival.The probabilistic sensitivity analysis showed that at a WTP threshold of three times China's per capita GDP in China in 2024(287,247 yuan/QALY),the probability of the ribociclib combination therapy being cost-effective was 100%.Conclusion In the context of the Chinese healthcare system,the combination therapy of ribociclib and fulvestrant is more cost-effective than fulvestrant monotherapy for the second-line treatment of postmenopausal patients with HR+/HER2-advanced metastatic breast cancer.

Objective To investigate the association between early peripheral perfusion index (PPI) and acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) following major noncardiac surgery. Methods This retrospective cohort study was conducted at a single center. Adult patients consecutively enrolled were those admitted to the ICU after major noncardiac surgery. PPI measurements were collected within the first 6 hours post-surgery. The primary outcome assessed was the occurrence of AKI within 7 days after surgery. Multivariate logistic regression analysis was employed to adjust for confounding factors,while receiver operating characteristic (ROC) curve analysis determined the most predictive cutoff PPI. Results The study included a total of 444 patients who underwent noncardiac surgery. The incidences of postoperative AKI and severe AKI were 9.23％ and 1.13％,respectively. Early postoperative PPI levels exhibited a skewed distribution,with a median value of 3.02 (2.02,4.24). After adjusting for various perioperative variables,PPI was found to be indepen-dently correlated with the occurrence of postoperative AKI (OR=0.734,95％ CI:0.580～0.930,P=0.010),as indicated by an area under the ROC curve of 0.6802 (95％ CI:0.6022～0.7582,P<0.001). Using a cutoff value of ≤ 2 .04 for PPI,the sensitivity and specificity for predicting postoperative AKI were determined to be approximately at 53.7％ and 77.2％ respectively. Further analysis revealed that patients with PPI ≤ 2.04 had a higher incidence of severe postoperative complications as well as prolonged mechanical ventilation duration and hospital stay. Conclusions A prompt reduction in postoperative PPI usage was found to be linked with the inci-dence of AKI occurring within 7 days following major noncardiac surgery.

With the extension of the global population's lifespan and the increasingly severe aging problem,cardio-vascular diseases have become the leading cause of death among the elderly population.Most cardiovascular diseases orig-inate from the formation of atherosclerotic plaques.In addition to common risk factors such as dyslipidemia,diabetes,hy-pertension,smoking,and obesity,circadian rhythm disruption is also regarded as an important but often overlooked risk factor for atherosclerosis.The circadian rhythm is involved in regulating key physiological processes such as inflammation and metabolism,which in turn affect the pathological processes of arteriosclerosis and thrombosis.In this process,the key genes that maintain the stability of the circadian rhythm,namely clock gene,play a crucial role.Clock gene have an important role in the pathological mechanism of atherosclerosis,and they may become potential new targets for the preven-tion and treatment of atherosclerosis.This paper reviews the latest research progress on the mechanism of action of clock gene in the occurrence and development of atherosclerosis.These findings may provide new ideas for the diagnosis and treatment of atherosclerosis.

Objective To investigate the clinical application value of blood routine parameters such as white blood cells(WBC),neu-trophils(NEU),lymphocytes(LYM),monocytes(MON),platelets(PLT),neutrophil to lymphocyte ratio(NLR),and platelet to lymphocyte ratio(PLR)and C-reactive protein(CRP)in children with influenza A(Flu A)virus infection.Methods 317 children with upper respiratory tract symptoms visited Department of Pediatrics,Affiliated Jiangning Hospital of Nanjing Medical University from September 2023 to May 2024 were retrospectively analyzed.According to the six kinds of nucleic acid test results of upper respiratory tract,the children were divided into the Flu A group(n=150)and disease control group(n=167).In addition,97 healthy children who underwent physical examination in our hospital during the same period were selected as the healthy control group.The finger blood of the children was collected for the detection of blood routine parameters and CRP.The Kruskal-Wallis H non-parametric test was used to compare the differences of these parameters among the three groups.The receiver operating characteristic(ROC)curve was drawn,and the area under the ROC curve(AUCROC)was used to evaluate the diagnostic value of each indicator for influenza A virus infection.Results The NLR and PLR in the Flu A group were significantly higher than those in the disease control group and healthy control group,while the levels of WBC and LYM were significantly lower than those in the disease control group and healthy control group(P＜0.05).The level of CRP in the Flu A group was higher than that in the healthy control group but lower than that in the disease control group(P＜0.05).The indicator with the best diagnostic efficacy for influenza A virus infection was LYM,whose AUCROC was 0.79.When the optimal diagnostic threshold was 1.55×109/L,its sensitivity and specificity were 0.620 and 0.837,respectively.Next were PLR and NLR,with AUCROC of 0.735 and 0.723,specificity of 0.754 and 0.826,and sensitivity of 0.693 and 0.553,respectively.The diagnostic efficacy of MON,PLT,and CRP was relatively low.The AUCROC of the combined detection of LYM,NLR,PLR,MON,PLT,and CRP for the diagnosis of influenza A virus infection could increase to 0.838.Conclusion The blood routine parameters of children with influenza A virus infection show a decrease in the level of LYM and an increase in NLR and PLR.The combined detection of LYM,NLR,PLR,MON,PLT,and CRP can improve the accuracy of early diagnosis of influenza A virus infection in children.

Objective:To analyze the relationship among serum levels of fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25-OH-VD) and osteoporosis in children.Methods:Eighty children with osteoporosis admitted to Affiliated Hosptial of Jining Medieal University from Jun. 2019 to Jun. 2024 were included as the observation group, and 60 healthy children who underwent physical examination during the same period were included as the control group. Serum FGF23 and 25-OH-VD levels were compared between the two groups, and bone mineral density and bone metabolism indexes [CTX-1, osteocalcin (OC) and N-terminal propeptide of type I precollagen (PINP) ] were detected. Pearson correlation was used to analyze the correlation among serum FGF23, 25-OH-VD, bone metabolism indexes and bone mineral density. Logistic regression model was used to analyze the risk factors of osteoporosis in children.Results:Serum FGF23 and CTX-1 levels in the observation group were significantly higher than those in the control group ( t=15.77, 7.56, P < 0.05), while serum 25-OH-VD, OC, PINP and BMD levels were significantly lower ( t=14.09, 2.70, 13.25, 3.63, P < 0.05) ; Pearson correlation analysis showed that BMD was not correlated with age, BMI and OC ( r=-0.07, -0.02, 0.01, P > 0.05), BMD was negatively correlated with FGF23 and CTX-1, and positively correlated with 25-OH-VD and PINP ( r=-0.35, -0.34, 0.41, 0.40, P < 0.05). The stepwise regression model showed that FGF23 and 25-OH-VD were the main factors affecting BMD ( t=-2.40, 9.02, P<0.05). Multifactor Logistic regression model showed that FGF23 and 25-OH-VD were related factors of osteoporosis in children ( OR=3.01,1.16, P<0.05) . Conclusion:Serum FGF23 level is higher and 25-OH-VD level is lower in children with osteoporosis, which is significantly correlated with bone mineral density and is a related factor for osteoporosis in children.