Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Objective To investigate the relationship between stationing years of personnel on an island and their traditional Chinese medicine(TCM)constitution,thus providing a reference for adjusting the health status of stationed personnel,preventing and treating diseases.Methods Based on The Scale of Constitution in Chinese Medicine Questionnaire,TCM constitution of 734 personnel stationed on an island was investigated.Pearson χ2 method was used for data analysis.Results Of the 734 personnel stationed on an island 345(47.0%)were of the balanced constitution type and 389(53.0%)were of the biased constitution types.Among the people with biased constitution types,composite constitution accounted for 80.5%(313 people)and the simple accounted for the rest(19.5%,76 people).The top three types of the biased were dampness heat(15.2%),qi deficiency(14.0%),and yin deficiency(10.7%).The distribution of TCM constitution types was significantly different in terms of stationing years on the island(P<0.05).There was a significant difference in the balanced type and yin deficiency type between people with stationing time≤2 years and>8 years(P<0.05).There was a significant difference in qi deficiency type and qi depression type between people with stationing time≤2 years and>5 years(P<0.05).Compared to people with stationing time≤2 years,significant difference was found in yang deficiency type in people with stationing time ranging from 2 to 5 years and those with>8 years(P<0.05).There were significant differences in the phlegm dampness type,blood stasis type,and specific diathesis type between people with stationing time≤2 years and people with stationing time ranging from>2～5 years and>8 years(P<0.05).There were significant differences in the dampness heat type between people with stationing time≤2 years and people with stationing time ranging from>5～8 years and>8 years,between pepole with stationing time ranging from>2～5 years and people with stationing time>8 years(P<0.05).Conclusion The dampness heat type,qi deficiency type and yin deficiency type are common biased TCM constitution in personnel stationed on islands.The longer the time spent on islands,the greater the possibility of forming biased constitution.

Bupivacaine is a long-acting local anesthetic widely used clinically,but its 6-8 hours duration is insufficient for postoperative analgesia.Designing drug dosage forms to prolong the action time of local anesthetics is the research content of local anesthetics.In 2011,the FDA approved a bupivacaine liposome preparation based on DepoFoam TM technology:Exparel,which can be used for more than 72 hours.This article reviewed the clinical safety research of Exparel and the research progress of its application in clinical postoperative analgesia.

In recent years， coronary microvascular disease （CMVD）， a main type of ischemic heart disease with high incidence and low diagnosis rate， has become a new research hotspot and received much clinical attention. The etiology of CMVD is complex and the symptoms are various. Traditional Chinese and Western medicine have different opinions on its pathogenesis and treatment plan. Western medicine believes that CMVD is related to structural abnormalities （such as microvascular remodeling， vascular invasion， lumen obstruction， sparse vascular vessel and perivascular fibrosis） and functional abnormalities （such as endothelial dysfunction， smooth muscle cell dysfunction， microvascular constriction， microvascular spasm， inflammation and autonomic nervous dysfunction） of coronary microvascular vessels as well as the extravascular factors （such as heart rate and blood pressure）. In clinics， conventional western medicines are usually used for empirical treatment， but with undesirable effects. Traditional Chinese medicine （TCM） believes that CMVD belongs to the category of "chest impediment"， "heart pain" and "collateral disease"， and the common syndromes include Qi deficiency and blood stasis， Qi stagnation and blood stasis， Qi and Yin deficiency， congealing cold in heart vessel， heart and spleen deficiency， blood stasis obstructing collaterals， combined phlegm and blood stasis， and liver and kidney deficiency， with a variety of treatment methods. Specifically， Chinese patent medicines， self-designed prescriptions， modified classical prescriptions and TCM characteristic therapies have achieved certain effects. This review discussed the risk factors， pathological mechanism， TCM etiology and pathogenesis and traditional Chinese and Western medicine treatment of CMVD， to provide reference for the study and treatment of CMVD.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved ¹O₂ generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

The blood-brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

Objective:To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors.Methods:Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out.Results:The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months.Conclusion:HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

With the aging of Chinese society and the deepening of the reform of the medical and health system， pharmaceutical professionals are committed to providing patient-centered， efficient and scientific pharmaceutical care. Continuous pharmaceutical care has become the focus of scholars in this field. In this paper， the concept， importance， dimensions and evaluation indicators of continuous pharmaceutical care， as well as the development status at home and abroad， are reviewed by literature research， and suggestions for development are put forward. The continuous pharmaceutical care has been relatively mature in some developed countries. But in China， due to its late development， it is urgent to explore and develop evaluation indicators suitable for China’s medical and health service system. The continuous pharmaceutical care in China is mainly based on the coordination between comprehensive medical institutions and primary medical institutions within the medical consortium， achieves orderly two-way referral between medical institutions according to the individual situation of patients， and provides individualized drug treatment management for patients during disease prevention， treatment and after treatment.It is suggested to homogenize the pharmaceutical care of medical institutions at different levels， promote the cooperation among the government， medical insurance， superior medical institutions， etc.， so as to improve the pharmaceutical care of primary medical institutions and accelerate the construction of a continuous pharmaceutical care system.

Objective:To evaluate the efficacy and safety of azacitidine combined with HAG regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy.Methods:Eighteen newly diagnosed elderly AML patients ineligible for intensive chemotherapy from July 2019 to September 2021 in the Second People's Hospital of Shenzhen were prospectively enrolled in this study. They were non-randomly divided into azacitidine combined with HAG regimen (AZA-HAG) group (9 cases) and decitabine combined with HAG regimen (DEC-HAG) group (9 cases). The primary endpoint of the study was overall response [complete remission (CR)+partial remission], and the secondary endpoints included CR + complete remission with incomplete count recovery (CRi), overall survival (OS) and drug safety. Kaplan-Meier method was used to analyze the OS.Results:The median age of 18 patients was 67 years old (60-77 years old) , and 8 of them were in high-risk group. After one course of treatment, the overall response and CR+CRi were observed in 7 of 9 patients in AZA-HAG group, and they were observed in 8 of 9 patients in DEC-HAG group, and there was no significant difference between the two groups (both P = 1.000). The median duration of CR+CRi was 7 months in both groups, and the median OS time was 12 months in both groups; there was no significant difference in OS between the two groups ( χ2 = 0.02, P = 0.895). In AZA-HAG group, 1 patient with TP53 mutation and 1 patient with ASXL1+RUNX1 mutation acquired CR, and 1 patient with NPM1 wild-type combined with FLT3-ITD and ASXL1 mutation did not respond. There was no significant difference in the incidence of grade 3-4 hematological adverse reactions between the two groups (all P < 0.05). Conclusions:Azacitidine combined with low-dose HAG regimen in the treatment of newly diagnosed elderly AML patients ineligible for intensive chemotherapy has satisfactory efficacy and long-term survival, and the adverse reactions can be tolerated.