Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.

Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.

Objective: To investigate the awareness of hepatitis C prevention and control knowledge and its influencing factors among female sex workers (FSWs) in Jiaxing City, Zhejiang Province. Methods: According to the HIV/AIDS Sentinel Surveillance Plan, FSWs at ages of 15 to 65 years monitored by the national AIDS surveillance sentinel in Jiaxing City were recruited, and demographic information, awareness of hepatitis C prevention and control knowledge and related behaviors were collected by questionnaire surveys. Factors affecting the awareness of hepatitis C prevention and control knowledge were identified by a multivariable logistic regression model. Results: A total of 430 questionnaires were allocated, and 412 were valid, with an effective rate of 95.81%. The respondents had a mean age of (28.58±4.93) years, and included 258 unmarried FSWs (62.62%), 344 with registered residence outside Zhejiang Province (83.50%), 212 with junior high school education or below (51.46%) and 243 from high-end entertainment places (58.98%). The overall awareness of hepatitis C prevention and control knowledge among FSWs was 20.39%, and the awareness of "Transfusion of blood containing hepatitis C virus may acquire hepatitis C" (38.83%) and the awareness of "tattooing, eyebrow tattooing and ear piercing in streets or small shops may infect hepatitis C" (38.11%) were relatively low. Multivariable logistic regression analysis identified marital status (divorced or widowed, OR=0.161, 95%CI: 0.054-0.482), educational level (high school or technical secondary school, OR=2.568, 95%CI: 1.446-4.560; junior college or above, OR=6.110, 95%CI: 2.658 -14.045) and grade of entertainment places (high-end entertainment places, OR=2.756, 95%CI: 1.525-4.982) as factors affecting the awareness of hepatitis C prevention and control knowledge among FSWs. Conclusion FSWs in Jiaxing City have a low awareness of hepatitis C prevention and control knowledge, especially lacking of knowledge about the transmission routes and prognosis of hepatitis C.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the binary coping experience of elderly patients with chronic non-specific low back pain and their spouse caregivers, and provide reference for targeted intervention strategies.Methods:A purposive sampling method was used to select 12 patients with low back pain and their spouses who received treatment in the spinal surgery department of Shanghai Tenth People's Hospital from December 2023 to February 2024 as the research subjects. Phenomenological research methods in qualitative research were used for semi-structured interviews, and thematic analysis was used to summarize data and extract themes.Results:Totally 12 patients aged 60-75 years old, 4 males and 8 females; 12 spouses aged 56-78. Based on the binary coping system interaction model, two themes and nine sub themes were extracted: negative coping (disasters, mutual negation, questioning fate, derivative marital conflicts) and positive coping (taking responsibility, mutual support, mutual comfort, looking forward to the future, open and constructive communication).Conclusions:Elderly patients with chronic non-specific low back pain and their spouse caregivers have both positive and negative coping strategies. Medical workers need to attach importance to providing positive binary coping guidance to patients and their spouses, while also intervening in the coping strategies of both spouses, so that they can better cope with the disease and improve the clinical outcomes of patients.

Objective:To explore the binary coping experience of elderly patients with chronic non-specific low back pain and their spouse caregivers, and provide reference for targeted intervention strategies.Methods:A purposive sampling method was used to select 12 patients with low back pain and their spouses who received treatment in the spinal surgery department of Shanghai Tenth People's Hospital from December 2023 to February 2024 as the research subjects. Phenomenological research methods in qualitative research were used for semi-structured interviews, and thematic analysis was used to summarize data and extract themes.Results:Totally 12 patients aged 60-75 years old, 4 males and 8 females; 12 spouses aged 56-78. Based on the binary coping system interaction model, two themes and nine sub themes were extracted: negative coping (disasters, mutual negation, questioning fate, derivative marital conflicts) and positive coping (taking responsibility, mutual support, mutual comfort, looking forward to the future, open and constructive communication).Conclusions:Elderly patients with chronic non-specific low back pain and their spouse caregivers have both positive and negative coping strategies. Medical workers need to attach importance to providing positive binary coping guidance to patients and their spouses, while also intervening in the coping strategies of both spouses, so that they can better cope with the disease and improve the clinical outcomes of patients.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin