OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

The intestine is a complex symbiotic system, and the gut microbiota is closely related to host health. Studies have indicated that the gut microbiota influences physiological functions of the host by producing a variety of metabolites, which act as signaling molecules and substrates for metabolic reactions in the host. Dysbiosis of the gut microbiota affects the abundance of gut microbiota-derived metabolites, thereby influencing host health by disrupting signal transduction in multiple organs. Additionally, dietary compounds can shape the gut microbiota, affecting gut microbiota-derived metabolite levels and regulating host metabolism. This article introduces the methods for mining gut microbiota-derived metabolites, reviews the roles of these metabolites in metabolic diseases and related dietary interventions. Which provides a perspective on the prevention and treatment of metabolic diseases by targeting these metabolites, enriching the knowledge on the role of gut microbiota in the regulation of host metabolism.
Gastrointestinal Microbiome/physiology* ; Humans ; Dysbiosis/microbiology* ; Metabolic Diseases/metabolism* ; Diet

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To investigate the advantages and safety of subxiphoid uniportal thoracoscopic thymectomy.Methods:From October 2014 to December 2019, a total of 308 patients diagnosed with early stage thymic epithelial tumor underwent uniportal thoracoscopic thymectomy were included. Subxiphoid group including 40 males and 37 females, aged 32-80 years old, mean age(58.0±11.8)years old. Intercostal group including 114 males and 117 females, aged 25-78 years old, mean age(54.8±11.4)years old. Short-term and long-term postoperative pain scores was compared in a propensity score matching analysis.Results:Propensity score analysis revealed that 62 patients treated with the subxiphoid approach and 62 patients treated with the lateral intercostal approach had the same baseline characteristics. There were no significant differences in lesion size, stage, pathological type, intraoperative blood loss, postoperative drainage volume and postoperative hospital stay between the two groups( P>0.05). Compared with those in the intercostal group, patients in the subxiphoid group yielded lower pain scores on the first day after operation and less patients with postoperative pain lasting more than 3 months. Patients required for additional analgesic therapy in subxiphoid group was less than intercostal group. One patient in subxiphoid group developed myasthenia after operation, which prolonged the duration of mechanical ventilation. No serious perioperative complications and death occurred in other patients. Conclusion:Subxiphoid uniportal thoracoscopic thymectomy is safe and feasible, it has the advantages of no injury to intercostal nerve and less short-term and long-term postoperative pain compared with intercostal approach.

OBJECTIVE： To provide reference for rational use of estradiol （E2） preparation in clinic. METHODS： The medical records of outpatients receiving assisted reproductive technology （ART） and E2 preparation [Estradiol valerate tablets （EV）， Complex packing estradiol tablets/estradiol and dydrogesterone tablets （EP）， Estradiol gel （EG）] were collected from the reproductive medicine center of a hospital during Jan. 2016-Mar. 2017. Taking drug instruction as standard， the rationality of medical records was evaluated from aspects of indication， route of administration， contraindication， usage and dosage， treatment course， etc. At the same time， these patients were followed up by telephone or outpatient service， and their pregnancy outcomes and ADR were summarized. RESULTS： A total of 12 646 prescriptions were collected， and 7 222， 3 912， 181 and 1 331 prescriptions used EV， EP， EG and EV+EP， respectively. The types of off-label use included over-indication， over-route and over-contraindication， and the rates of off-label use rates were 100％， 11.73％ and 43.60％， respectively. A total of 5 868 ART patients were involved； 439 patients received fresh embryo transplantation， and 5 429 patients received frozen-thawed embryo transplantation， involving 720 and 11 926 prescriptions， respectively. The rates of off-label use of above E2 preparations were 100％ （except for fresh embryo transplantation patients using EG）. As of Feb. 2018， the infant-holding rates of ART patients using EV， EP， EG and EV+EP were 85.29％， 85.37％， 86.36％ and 85.45％， respectively. No relevant ADR and neonatal birth defect was found. CONCLUSIONS： The phenomenon of off-label use of E2 preparations is widespread in the reproductive medicine center of the hospital. Although there is no indication of related safety risks， evidence-based evaluation should be carried out by enlarging the sample size in clinical practice， and careful use.

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

Objective To analyze the clinical value of immature granulocytes in peripheral blood for prediction of persistent systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis (AP). Methods 1 973 patients with AP in Hunan People's Hospital from 2012 to 2017 were retrospectively enrolled and divided by SIRS duration into the persistent SIRS group, temporary SIRS group and non-SIRS group. The independent risk factor for persistent SIRS in AP patients was evaluated by Logistic regression analysis, and predictive value of immature granulocytes for persistent SIRS in AP patients was analyzed by the receiver operating characteristic (ROC) curve. Results These 1 973 AP patients (1 165 males, 59.0%) with an average age of 49 (40, 60) years old, including 288 persistent SIRS, 189 temporary SIRS and 1 496 non-SIRS cases. There was no significant difference in gender, age and etiology among three groups. Compared with non-SIRS group, more severe symptoms were observed in the temporary and persistent SIRS groups. Moreover, The acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), CT severity index (CTSI), multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS) incidence, mortality and C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT) and immature granulocytes in persistent SIRS group were further higher than those in the temporary SIRS group [APACHEⅡ: 9 (6, 12) vs. 5 (3, 7), CTSI: 6 (4, 6) vs. 4 (3, 6), MOF incidence: 92.0% vs. 32.8%, ARDS incidence: 39.9% vs. 10.1%, morbidity: 11.1% vs. 4.2%, CRP (mg/L): 25.00 (0.80, 212.25) vs. 0.80 (0.80, 123.50), WBC (×109/L): 15.17±6.78 vs. 14.84±5.86, PCT (μg/L): 0.23 (0.10, 1.76) vs. 0.10 (0.10, 0.31), immature granulocytes: 1.95 (0.90, 4.95) % vs. 0.80 (0.40, 2.10) %, all P < 0.05]. Logistic regression analysis showed that besides pancreatic necrosis, WBC and CRP, immature granulocyte was an independent risk factor for persistent SIRS associated with AP [odds ratio (OR) = 1.844, 95% confidence interval (95%CI) = 1.372-2.220]. ROC curve showed that immature granulocytes had better predictive value for persistent SIRS, the area under the curve (AUC) was 0.806, which was significantly higher than the APACHEⅡ (AUC = 0.783), CTSI (AUC = 0.752), PCT (AUC = 0.676), CRP (AUC = 0.677), WBC (AUC = 0.644). The cut-off value of immature granulocyte was 0.65%, the sensitivity was 84.0%, the specificity was 66.3%, the positive predictive value was 62.4%, and the negative predictive value was 76.3%. Conclusion Immature granulocyte in peripheral blood is a potential indicator for persistent SIRS in AP patients.

Objective: To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease. Methods: Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs. Results: The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment (P<0.001). Conclusion The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.

OBJECTIVETo observe the effects of electroacupuncture (EA) on pain behavior in rats with bone cancer pain and morphine tolerance, and to explore partial action mechanism.

METHODSForty-two SD healthy female rats were randomly divided into a sham operation group (7 rats), a bone cancer pain group (8 rats), a morphine tolerance group (9 rats), an EA group (9 rats) and a sham EA group (9 rats). The rats in the sham operation group were treated with injection of phosphate buffer saline at medullary cavity of left-side tibia, and the rats in the remaining groups were injected with MRMT-1 breast cancer cells. After operation, no treatment was given to rats in the sham operation group and bone cancer pain group. 11 days after operation, rats in the morphine tole-rance group, EA group and sham EA group were treated with intraperitoneal injection of morphine hydrochloride, once every 12 hours, for 11 days to establish the model of bone cancer pain and morphine tolerance. One day after the establishment of this bone cancer pain model, the rats in the morphine tolerance group were injected with morphine, once every 12 hours (9:00 a.m. and 9:00 p.m.) for 7 days; the rats in the EA group and sham EA group were injected with morphine at 9:00 a.m., and treated with EA (2 Hz/100 Hz) and sham EA (only injected into the subcutaneous tissue) at bilateral "Zusanli" (ST 36) and "Kunlun" (BL 60), 30 min per treatment, once a day for 7 days. One day before cancer cell injection, 6 days, 8 days, 10 days after operation, after 30 min on 1 days, 5 days, 9 days, 11 days of morphine injection, and after 30 min on 1 days, 3 days, 5 days, 7 days of EA treatment, the paw withdrawal threshold (PWT) was measured in each group. On 11 day of morphine injection, HE staining was applied to observe the morphology and structure change of tibia in the sham operation group, bone cancer pain group and morphine tolerance group, random 2 rats in each group. On 7 days of EA treatment, fluorescent immunohistochemical method was applied to observe the expression of μ-opioid receptor positive cells in nucleus ceruleus in each group, random 4 rats in each one.

RESULTSAfter 10 days of the cancer cells injection, the PWT of 28 rats of bone cancer pain model (8 rats in the bone cancer pain group, 8 rats in the morphine tolerance group, 6 rats in the EA group and 6 rats in the sham EA group) was significantly lower than that of 7 rats in the sham operation group (<0.01). After one day of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was higher than that of the bone cancer pain group (all<0.01); on 11 d of morphine injection, the PWT of the morphine tolerance group, EA group and sham EA group was not significantly different from that of the bone cancer pain group (all>0.05). On 11 d of morphine injection, the tumor induced by cancer cells was observed in upper 1/3 tibia in the bone cancer pain group and morphine tolerance group, and the marrow cavity was filled with MRMT-1 cancer cells; no abnormal change was observed in the sham operation group. On 1 d, 3 d, 5 d and 7 d of EA treatment, the PWT of the cancer pain group, morphine tolerance group and sham EA group was lower than that of the EA group (all<0.01). On 7 d of EA treatment, the positive expression of MOR in nucleus ceruleus in the cancer pain group, morphine tolerance group, EA group and sham EA group was lower than that in the sham operation group (<0.01,<0.05), and that in the cancer pain group, morphine tolerance group and sham EA group was lower than that in the EA group (all<0.01).

CONCLUSIONSEA can improve mechanical pain threshold in rats with bone cancer pain-morphine tolerance, and improve the abnormal pain, which is likely to be involved with improvement of the MOR positive cells expression in nucleus ceruleus by EA.

Objective To systematically assess the efficacy and safety of electroacupuncture for trigeminal neuralgia. Method Randomized controlled trials of a electroacupuncture treatment for trigeminal neuralgia were sought by a computer search of CNKI,Wan Fang Data,VIP,CBM,PubMed,EMbas and The Cochrane Library.The retrieval time limit was from March 1996 to March 2016. Two reviewers sifted the literature and extracted data independently according to the inclusion and exclusion criteria andthen assessed the riskofbias of the included literatureusing the Cochrane risk of bias assessment tool.Ameta-analysis was made using RevMan 5.3.Result Finally, 12 articles were included with atotal of 847 subjects.The results ofmeta-analysis showed that the total efficacy rate was higher in the electroacupuncture group than in the control group [OR=4.04,95%CI(2.67, 6.13),P<0.00001].There were no statistically significant differences in the VAS score [MD=﹣0.06,95%CI(﹣0.59, 0.47),P=0.82] and the recurrence rate [OR=0.64,95%CI(0.05,7.45),P=0.54] between the electroacupuncture and control groups.Conclusion The currentlimited evidenceshows that the total efficacy rate fortrigeminal neuralgiais higher in the electroacupuncture group than in the control group.There are no statistically significant differences in the VAS score and the recurrence rate of trigeminal neuralgia between the electroacupuncture and control groups of patients.But the conclusions need more high-qualitytrials for validation owing to the limitation of the sample size of the included studies.