ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Background With the aging of China's population, cognitive impairment in the elderly is receiving increasing public attention. Screening and intervention of people with mild cognitive impairment (MCI) are of great significance to prevent and reduce the occurrence of cognitive impairment. Objective To understand the prevalence and explore potential influencing factors of MCI in the elderly in Songjiang District, Shanghai, and to provide scientific basis for promoting early screening of cognitive impairment and precise intervention of MCI in the elderly in this area. Methods A cross-sectional study design was adopted. From August to October 2022, using multi-stage random sampling, 1800 elderly residents aged 60 years and above were screened for cognitive impairment in 6 neighborhood/village committees in 6 towns in Songjiang District. The survey questionnaires included a sociodemographic questionnaire, a health status and lifestyle questionnaire, the Instrumental Activities of Daily Living (IADL), the Patient Health Questionnaire (PHQ-9), and the Mini-Mental State Examination (MMSE). Prevalence rates of MCI among the elderly by selected social demographic characteristics, health status, and lifestyle were estimated, and potential influencing factors of MCI were evaluated by binary logistic regression. Results A total of 209 elderly residents with MCI and 1591 healthy elderly residents were detected, and the prevalence of MCI in the elderly aged 60 and above was 11.6% in Songjiang District. Being physically active (OR=0.556, 95%CI: 0.399, 0.774) reduced the risk of MCI. Illiteracy (OR=1.810, 95%CI: 1.239, 2.644), primary school education level (OR=3.454, 95%CI: 2.342, 5.092), non-participation in social activities (OR=1.945, 95%CI: 1.360, 2.781), IADL damaged (OR=3.173, 95%CI: 2.137, 4.712), and depression (OR=1.957, 95%CI: 1.112, 3.443) increased the risk of MCI (P＜0.05). Conclusion The prevalence of MCI among the elderly in Songjiang District is lower than the national average. Educational level, physical activity, participation in social activities, IADL, and depression may be the influencing factors of MCI in the elderly. It is recommended to carry out early screening, early detection, and early intervention for cognitive impairment in the elderly. Improving involvement in physical exercise and increasing participation in social activities are encouraged. Special attention should be paid to the needs of vulnerable groups such as low education level and disabled elderly during a community MCI intervention program.

OBJECTIVE To study the extraction technology of Sophora flavescens-Phellodendron chinense drug pair and provide a reference for the development of new drugs for the treatment of anorectal diseases. METHODS Using the contents of total alkaloids of S. flavescens （matrine+oxymatrine）， berberine hydrochloride and total flavonoid， and extract yield as evaluation indicators， analytic hierarchy process-entropy weight method was used to calculate the weight coefficient of each indicator， and was combined with Box-Behnken design-response surface method to study the extraction technology of S. flavescens-P. chinense drug pair and verify it. RESULTS The optimal extraction technology of S. flavescens-P. chinense drug pair was immersed in 12-fold amount of 58% ethanol for 30 minutes and extracted twice， each time for 120 minutes. The relative error between the verification experimental results and the predicted value was 1.88%. CONCLUSIONS The obtained extraction technology is stable and feasible and can provide reference for the application of S. flavescens-P. chinense drug pair and development of new drugs.

Objective To investigate the changes of sex hormone levels in polycystic ovary syndrome(PCOS)in infertile population after the assisted reproductive technology treatment,and to provide an evidence for the choice of the treatment.Methods The medical data of patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2016 to June 2021 were collected and divided into PCOS group(103)and non-PCOS group(589)according to whether they were diagnosed with PCOS,and the sex hormone changes of the two groups were compared.Results The patients in PCOS group were younger and had the higher BMI,more sinus follicles,higher AMH value,and lower total Gn usage.The number of LH/FSH>2 in PCOS group was higher than that in non-PCOS group(P<0.05).After the treatment,LH in both groups decreased,FSH,E2 and(P<0.05)increased;The difference of LH and E2 before and after the treatment in PCOS group was greater than that in non-PCOS group<0.05).Conclusion Compared with non-PCOS infertile patients,the changes of sex hormone indexes in PCOS infertile patients before and after the treatment were more obvious.In order to obtain the better clinical effect in patients with polycystic ovaries,it is recommended to pay attention to the changes of related sex hormone levels in the course of subsequent treatment,and choose a reasonable treatment plan.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P<0.05). The serum Vit A(0.34±0.18 μmol/L)and bFGF(0.44±0.18 ng/L)levels in stage 3-5 ROP group were lower than those in the group without ROP(P<0.05). The serum Vit A and bFGF levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(P<0.05). At 35d postnatal, the serum Vit A(0.33±0.19 μmol/L)and bFGF(0.39±0.19 ng/L)levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(0.43±0.16 μmol/L and 0.48±0.17 ng/L; all P<0.05). According to the ROC curve drawn by serum Vit A, the AUC value was 0.853, the maximum Youden index was 0.68, the best sensitivity was 73%, and the best specificity was 95%. According to the ROC curve drawn by serum bFGF, the AUC value was 0.828, the maximum Youden index was 0.58, the best sensitivity was 90%, and the best specificity was 68%. According to the ROC curve drawn by serum Vit A combined with bFGF, the AUC value was 0.917, the maximum Youden index was 0.70, the best sensitivity was 70%, and the best specificity was 100%.CONCLUSION: Serum Vit A and bFGF levels are sensitive and effective indicators for predicting ROP. If the serum Vit A or bFGF levels are lower in premature infants or low birth weight infants, it may indicate the higher probability of ROP and its pathological stages. In addition, the clinica value of serum Vit A combined with bFGF in the diagnosis of ROP is higher than that of Vit A or bFGF alone, and the misdiagnosis rate is reduced.

Galectin-9 （Gal-9） is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.

Objective To explore the correlation between the total burden of cerebral small vessel disease and poor prognosis of branch atheromatous disease(BAD)in elderly patients.Methods A total of 114 BAD patients admitted to Shanghai Eighth People's Hospital between January 2021 and March 2023 were enrolled,and according to mRS score at 90 d after onset,they were divided into a good prognosis group(mRS score ≤2,67 cases)and a poor prognosis group(mRS score＞2,47 cases).The clinical and imaging characteristics were analyzed,and the relationship between total cerebral small vessel disease burden and clinical prognosis of BAD was investigated using lo-gistic regression analysis.ROC curve analysis was used to determine the threshold of the total cere-bral small vessel disease burden for predicting adverse outcomes and to evaluate its sensitivity and specificity.Results The good prognosis group had younger age,smaller proportion of diabetes,lower SBP,NIHSS score at admission and white matter hyperintensities,and reduced ratio of cerebral microbleeds than the poor prognosis group(P＜0.05,P＜0.01).Statistical difference was observed in the total cerebral small vessel disease burden between the two groups(P＜0.01).Binary logistic regression analysis showed that the total cerebral small vessel disease burden score and NIHSS score at admission were independent predicators of poor prognosis in BAD patients(OR=3.350,95％CI:1.439-7.798,P=0.005;OR=2.814,95％CI:1.586-4.993,P=0.001).ROC curve analysis indicated that the total cerebral small vessel disease burden had a cut-off val-ue of 1.5,and the sensitivity and specificity for predicting poor prognosis was 63.8％and 86.6％,respectively,for BAD patients.Conclusion The total cerebral small vessel disease burden is an in-dependent predictor for poor prognosis of BAD patients.