Polycystic ovary syndrome （PCOS） is a common gynecological endocrine and reproductive disorder，with the main clinical manifestations including ovulation failure，insulin resistance，hyperandrogenism，and obesity. Its occurrence and development are closely related to cellular regulatory mechanisms such as apoptosis，autophagy，oxidative stress，and inflammatory response. Autophagy，as a clearance mechanism that maintains cellular homeostasis，plays a crucial role in maintaining the growth，development，and maturation of oocytes. Exploring the mechanism of autophagy during the occurrence and development of diseases can help develop treatment methods for PCOS by regulating autophagy. Studies have shown that autophagy plays an important role in the pathogenesis of PCOS，and it can affect the occurrence and development of PCOS through multiple pathways，levels，and targets. Traditional Chinese medicine （TCM） regulates autophagy in ovarian granulosa cells or endometrium of patients with PCOS by targeting the expression of autophagy signaling pathways，regulatory factors，and non-coding single-stranded RNA molecules，thereby alleviating inflammation，regulating metabolism disorders，and balancing hormone levels in PCOS. Accordingly，TCM can ameliorate pathological conditions such as insulin resistance，hyperandrogenism，and ovulation failure in PCOS. This article summarizes the TCM formulas and extracts for the treatment of PCOS，as well as the main autophagy pathways and regulatory factors involved，aiming to provide reference and suggestions for the future treatment of PCOS with TCM by regulating autophagy.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

OBJECTIVE: To observe the skin surface temperature at the related back-shu points in the patients with the different levels of pulmonary ventilation function in chronic persistent asthma, and to explore the correlation between the skin temperature at the back-shu points and pulmonary ventilation function indexes based on "lung governing the skin and hair". METHODS: Sixty-one patients with chronic persistent asthma, based on the level of pulmonary ventilation function, were assigned into a reduced pulmonary ventilation function group (reduced function group, 32 cases) and a normal pulmonary ventilation function group (normal function group, 29 cases). In the two groups, the skin surface temperature was measured in the sites of bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23); and the pulmonary ventilation function indexes (the percentage of predicted value of forced vital capacity [FVC%pred], the percentage of predicted value of forced expiratory volume in the first second [FEV1%pred], the percentage of predicted value of FEV1/FVC [FEV1/FVC%pred] and the percentage of predicted value of the peak expiratory flow [PEF%pred]) were recorded. The correlation between the skin surface temperature of acupoints and pulmonary ventilation function was analyzed. RESULTS: Compared with the normal function group, the surface skin temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was higher in the reduced function group (P<0.05, P<0.01). Compared with the normal function group, FEV1%pred, FEV1/FVC%pred and PEF%pred were decreased in the reduced function group (P<0.001). There was no significant difference in FVC%pred between the two groups (P>0.05). The skin surface temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was negatively correlated with FVC%pred, FEV1%pred, FEV1/FVC%pred and PEF%pred in 61 patients with chronic persistent asthma (P<0.001, P<0.01, P<0.05). CONCLUSION The skin surface temperature at back-shu points is elevated in line with the the decline of pulmonary ventilation function in the patients with chronic persistent asthma, presenting a negative correlation with pulmonary ventilation function indexes. It is preliminarily verified that back-shu point is characterized by reflecting the visceral disorders.
Humans ; Female ; Male ; Asthma/therapy* ; Middle Aged ; Adult ; Skin Temperature ; Lung/physiopathology* ; Acupuncture Points ; Pulmonary Ventilation ; Aged ; Chronic Disease/therapy* ; Young Adult ; Hair

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

In order to realize the quantitative assessment of muscle strength in hand function rehabilitation and then formulate scientific and effective rehabilitation training strategies, this paper constructs a multi-scale convolutional neural network (MSCNN) - convolutional block attention module (CBAM) - bidirectional long short-term memory network (BiLSTM) muscle strength prediction model to fully explore the spatial and temporal features of the data and simultaneously suppress useless features, and finally achieve the improvement of the accuracy of the muscle strength prediction model. To verify the effectiveness of the model proposed in this paper, the model in this paper is compared with traditional models such as support vector machine (SVM), random forest (RF), convolutional neural network (CNN), CNN - squeeze excitation network (SENet), MSCNN-CBAM and MSCNN-BiLSTM, and the effect of muscle strength prediction by each model is investigated when the hand force application changes from 40% of the maximum voluntary contraction force (MVC) to 60% of the MVC. The research results show that as the hand force application increases, the effect of the muscle strength prediction model becomes worse. Then the ablation experiment is used to analyze the influence degree of each module on the muscle strength prediction result, and it is found that the CBAM module plays a key role in the model. Therefore, by using the model in this article, the accuracy of muscle strength prediction can be effectively improved, and the characteristics and laws of hand muscle activities can be deeply understood, providing assistance for further exploring the mechanism of hand functions .
Neural Networks, Computer ; Humans ; Hand Strength/physiology* ; Support Vector Machine ; Muscle Strength/physiology* ; Hand/physiology* ; Convolutional Neural Networks

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

ObjectiveTo explore the characteristics of circadian rhythm of blood pressure in patients with masked hypertension （MH） and its relationship with twelve two-hour peirods， providing a basis for early detection and intervention of MH. MethodsPatients who underwent 24-hour ambulatory blood pressure examination in the ambulatory blood pressure room of Jiangsu Province Hospital of Chinese Medicine from January to December 2022 were enrolled， and according to their outpatient blood pressure measurements， 24-hour ambulatory blood pressure monitoring and follow-up survey results， the MH， essential hypertension （EH） and normal blood pressure groups were classified， with 50 cases in each group. The general data， office blood pressure and 24-hour ambulatory blood pressure monitoring data were collected. The circadian rhythm of blood pressure including 24-hour average systolic blood pressure （24h SBP）， daytime average systolic blood pressure （d SBP）， nighttime average systolic blood pressure （n SBP）， 24-hour average diastolic blood pressure （24h DBP）， daytime average diastolic blood pressure （d DBP）， and nighttime average diastolic blood pressure （n DBP） were compared among the groups， and the nighttime blood pressure dipping percentage was calculated. The type of circadian rhythm was determined based on the nighttime blood pressure dipping percentage. The variability of blood pressure including 24h SBP standard deviation （24h SBP-SD）， d SBP standard deviation （dSBP-SD）， n SBP standard deviation （nSBP-SD）， 24h DBP standard deviation （24h DBP-SD）， d DBP standard deviation （dDBP-SD）， and n DBP standard deviation （nDBP-SD） were compared among groups， and the corresponding coefficient of variation （CV）， that is， 24h SBP-CV， d SBP-CV， n SBP-CV， 24h DBP-CV， d DBP-CV and n DBP-CV， were calculated. Based on the 24-hour ambulatory blood pressure monitoring results， the twelve two-hour average SBP and DBP in each group were calculated and compared. Simultaneously， patients with EH were divided into grades 1， 2， and 3 for further stratified analysis. ResultsThe age of the MH group was significantly higher than that of the EH group and the normal blood pressure group （P＜0.01）. The body mass index （BMI） and the proportion of smoking and alcohol consumption in the MH group and the EH group were significantly higher than those in the normal blood pressure group （P＜0.05 or P＜0.01）. In the normal blood pressure group， there were 49 dipper patterns （98.0%） and one non-dipper pattern （2.0%）； in the MH group， there were two dipper patterns （4.0%）， 29 non-dipper patterns （58.0%） and 19 reverse-dipper patterns （38.0%）； in the EH group， there were 20 dipper patterns （40.0%）， 23 non-dipper patterns （46.0%） and seven reverse-dipper patterns （14.0%）. Compared to the normal blood pressure group， the groups of MH and EH had significantly decreased proportion of dipper pattern and increased proportion of non-dipper and reverse-dipper pattern （P＜0.01）； the proportion of dipper pattern in the MH group was lower than that in the EH group， while the proportion of reverse-dipper pattern was higher （P＜0.01）. Compared to those in the normal blood pressure group， n SBP and n DBP in the MH group， as well as the the average SBP and average DBP at Zi hour （子时， 23：00-1：00）， Chou hour （丑时， 1：00-3：00）， Yin hour （寅时， 3：00-5：00）， Mao hour （卯时， 5：00-7：00） and average SBP at Hai hour （亥时， 21：00-23：00） in the MH group increased，while the average DBP at Si hour （巳时， 9：00-11：00） decreased （P＜0.01）； 24h SBP， 24h DBP， d SBP， d DBP， n SBP， and n DBP，d SBP-SD， n SBP-SD，n DBP-SD increased， as well as the average SBP and average DBP at twelve two-hour periods increased in the EH group，while the 24h SBP-CV， 24h DBP-CV，and d DBP-CV in the EH group decreased（P＜0.05 or P＜0.01）. The EH group had higher 24h SBP， 24h DBP， d SBP， d DBP， n SBP， n DBP， 24h DBP-SD and n DBP-SD ， as well as higher average SBP and DBP at all twelve two-hour periods， and lower d DBP-CV than the MH group（P＜0.05 or P＜0.01）. The EH group had 18 cases of grade 1 （36.0％）， 19 cases of grade 2 （38.0％） and 13 cases of grade 3 （26.0％）， with no significant differences among groups （P＞0.05）. ConclusionThe circadian rhythm of blood pressure in MH patients are mostly non-dipper and reverse-dipper patterns， and the abnormal elevation of blood pressure is obvious at Zi hour， Chou hour， Yin hour and Mao hour （23：00-7：00）.

Diabetic retinopathy(DR)is one of the major complications of diabetes mellitus, characterized by neurodegeneration and microangiopathy. Currently, the treatment of DR is mainly focused on the management of late complications and has not achieved the desired clinical outcome. Evidence suggests that the PI3K/AKT pathway, as one of the important intracellular signaling pathways during the cell cycle, is involved in the whole process of DR pathogenesis. This article focuses on the structural composition, activation and blocking pathways, conduction pathways, regulatory mechanisms and biological functions of the PI3K/AKT signaling pathway to review its role in DR and to explore the potential of targeting the PI3K/AKT pathway for the treatment of DR.