OBJECTIVES: To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. METHODS: Forty male SD rats were randomly assigned to control group, model group, Najia group and Nazi group (n=10). In the latter 3 groups, rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test. After modeling, the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine. Pathological changes in the hypothalamic tissue of the rats were examined with HE staining, and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Immunohistochemistry was used to detect the expressions of GABAA receptors (GABAARs) in the hypothalamus, and the expression levels of glutamate decarboxylase (GAD65/67) and glutamine synthetase (GS) were determined with Western blotting. RESULTS: Compared with the model group, the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus. Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia. CONCLUSIONS Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism* ; Sleep Initiation and Maintenance Disorders/therapy* ; Glutamine/metabolism* ; Glutamic Acid/metabolism* ; Acupuncture Therapy ; Hypothalamus/metabolism* ; Receptors, GABA-A/metabolism* ; Acupuncture Points

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C₁₈ column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min^-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.

ObjectiveTo establish and validate a clinical prediction model for 1-year major adverse cardiovascular events（MACEs）risk after percutaneous coronary intervention （PCI） in coronary heart disease （CHD） patients with blood stasis syndrome. MethodThe consecutive CHD patients diagnosed with blood stasis syndrome in the Department of Integrative Cardiology at China-Japan Friendship Hospital from September 1， 2019 to March 31， 2021 were selected for a retrospective study， and basic clinical features and relevant indicators were collected. Eligible patients were classified into a derivation set and a validation set at a ratio of 7∶3， and each set was further divided into a MACEs group and a non-MACEs group. The factors affecting the outcomes were screened out by least absolute shrinkage and selection operator （Lasso） and used to establish a logistic regression model and identify independent prediction variables. The goodness-of-fit of the model was evaluated by the Hosmer-Lemeshow test， and the area under curve （AUC） of the receiver operating characteristic （ROC） curve， calibration curve， decision curve analysis （DCA）， and clinical impact curve （CIC） were employed to evaluate the discrimination， calibration， and clinical impact of the model. ResultA total of 731 consecutive patients were assessed and 404 eligible patients were enrolled， including 283 patients in the derivation set and 121 patients in the validation set. Lasso identified ten variables influencing outcomes， which included age， sex， fasting plasma glucose （FPG）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， homocysteine （Hcy）， brachial-ankle pulse wave velocity （baPWV）， flow-mediated dilatation （FMD）， left ventricular ejection fraction （LVEF）， and Gensini score. The multivariate Logistic regression preliminarily identified age， FPG， TG， Hcy， LDL-C， LVEF， and Gensini score as the independent variables that influenced the outcomes. Of these variables， male， high FMD and high LVEF were protective factors， and the rest were risk factors. The prediction model for 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome showed χ²=12.371 （P=0.14） in Hosmer-Lemeshow test and the AUC of 0.90. With the threshold probability > 10%， the model showed better prediction performance for 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome than for that in all the patients. With the threshold probability > 60%， the estimated value was much closer to the real number of patients. ConclusionThe established clinical prediction model facilitates the early prediction of 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome， which can provide ideas for the precise treatment of CHD patients after PCI and has guiding significance for improving the prognosis of the patients. Meanwhile， multi-center studies with larger sample sizes are expected to further validate， improve， and update the model.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

It has been revealed that hypoxia is dynamic in hypertrophic scars; therefore, we considered that it may have different effects on hypoxia-inducible factor-1α (HIF-1α) and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1α and p53, which is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1α and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1α or p53 gene expression or triggered overexpression to investigate the changes of HIF-1α and p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1α, p53, and autophagy-related proteins were assayed using western blotting and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using cell counting kit-8 (CCK-8) and 5-bromo-2'-deoxyuridine (BrdU) staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1α and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1α expression increased in parallel with autophagosome formation. Under hypoxia, HIF-1α expression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1α knockdown downregulated autophagy, proliferation, and p300-bound HIF-1α, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1α, whereas p53 overexpression resulted in the same effects and reduced HIF-1α. Our results suggest a teeterboard-like conversion between HIF-1α and p53, which is linked with scar hyperplasia and regression.
Apoptosis ; Autophagy ; Cell Hypoxia ; Fibroblasts/metabolism* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Tumor Suppressor Protein p53/metabolism*

Background Because of high working intensity, high responsibility, and unexpected situations, health care workers may suffer great work pressure, which may lead to health damage. Objective To explore the self-rated health status and its influencing factors such as demographic and occupational-related factors of medical staff in Lanzhou. Methods In-service medical staff were selected by using cluster random sampling method from 18 public hospitals in Lanzhou City and were investigated with a self-made questionnaire and the Self-rated Health Measurement Scale (SRHMS). SRHMS includes 48 items in 10 dimensions, which are divided into three sub-scales of physical health, mental health, and social health, and another independent dimension is overall health. The scores were converted into a percentage scale and expressed as the percentage of measured score to full score; a higher score indicated better health, and >70% was considered good health status. t test, Kruskal-Wallis H test, and Spearman correlation were used to analyze the scores of SRHMS and the demographic and occupational-related factors affecting the scores of physical, mental, and social health sub-scales. Results A total of 2989 valid questionnaires were recovered. There were statistically significant differences in total score and the scores of physical, mental, and social health among medical staff of different age, educational background, length of service, and weekly working hours groups (P < 0.05). The percentage of total score to full score in the medical staff was 71.41%, but the scores of physical, mental, and social health sub-scales and total scale of selected participants were all lower than the corresponding domestic norms (t=−3.323, −12.283, −7.157, −9.659, P < 0.05); the percentage of psychological symptoms and negative emotions in mental health scale to full score was the lowest, only 58.39%. Educational background, length of service, and weekly working hours were negatively correlated with physical health score (r=−0.061, −0.060, −0.165, P < 0.05); professional title was positively correlated with mental health score (r=0.045, P < 0.05), while educational background and weekly working hours were negatively correlated with it (r=−0.051, −0.172, P < 0.05). Monthly income, professional title, and length of service were positively correlated with social health score (r=0.040, 0.049, 0.071, P < 0.05), while educational background and weekly working hours were negatively correlated with it (r=−0.038, −0.110, P < 0.05). Conclusion The self-rated health status of selected medical staff in Lanzhou is generally good, but lower than that of the norm, especially the mental health score is the lowest. The self-rated health score of total scale is correlated with education, length of service, professional title, and working time per week.

Eucommiae Folium(EF),a traditional Chinese medicine,has been used to treat secondary hypertension,including renal hypertension and salt-sensitive hypertension,as well as hypertension caused by thoracic aortic endothelial dysfunction,a high-fat diet,and oxidized low-density lipoprotein.The antihyperten-sive components of EF are divided into four categories:flavonoids,iridoids,lignans,and phenyl-propanoids,such as chlorogenic acid,geniposide acid and pinoresinol diglucoside.EF regulates the occurrence and development of hypertension by regulating biological processes,such as inhibiting inflammation,regulating the nitric oxide synthase pathway,reducing oxidative stress levels,regulating endothelial vasoactive factors,and lowering blood pressure.However,its molecular antihypertensive mechanisms are still unclear and require further investigation.In this review,by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology,we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension,the related components,and underlying mechanisms.The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component,multi-target and multi-pathway mechanism.In particular,we discussed the role of EF tar-gets in the treatment of hypertension,including epithelial sodium channel,heat shock protein70,rho-associated protein kinase 1,catalase,and superoxide dismutase.The relevant signal transduction path-ways,the ras homolog family member A(RhoA)/Rho-associated protein kinase(ROCK)and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase/eNOS/NO/Ca2+pathways,are also discussed.

Objective To detect the serum level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF),a significant metabolite offish oil,in subjects with normal glucose tolerance (NGT) in local communities,and to investigate the association of CMPF with fatty acid metabolism.Methods A total of 272 NGT participants from screening for diabetes in Shanghai in 2013 were enrolled.Anthropometric measurements,biochemical evaluation,and questionnaire interview were performed for all the participants.The participants were divided into normal weight group [body mass index (BMI) ≤23.9 kg/m2,n =143] and overweight/obesity group (BMI ≥ 24 kg/m2,n =129).The serum CMPF concentrations were determined using an enzyme-linked immunosorbent assay.Results Serum CMPF level in overweight/obesity group was lower than that in normal weight group [96.50 (46.11,169.56) μmol/L vs 153.20 (83.16,282.97) μmol/L,P＜0.05].The serum CMPF level was negatively correlated with BMI (r =-0.256,P＜0.01),triglycerides (r =-0.175,P =0.004),and free fatty acid (r =-0.126,P =0.041) according to bivariate correlation analyses.A multivariate stepwise linear regression analysis showed that the serum CMPF level was independently associated with BMI,triglycerides,free fatty acid,and HbA1C.A logistic regression analysis showed that the CMPF was a protective factor against obesity (OR =0.324,95％ CI 0.158,0.664).Conclusion Serum CMPF level is reduced in overweight/obese subjects.CMPF is beneficial to lipid metabolism.

Objective: By use of Meta analysis to compare efficacy, safety and compliance of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) on allergic rhinitis (AR). Methods: Cochrane Library, Pubmed, Embase, CNKI Database, Wan Fang and Chinese Sci-tech Journal Database (from established time to May of 2018) were searched for trials about the AR treated by SCIT and SLIT. The relevant literatures were screened, and the randomized controlled studies were chosen. Nasal symptom scores, visual analogue scale (VAS) scores, adverse reactions and compliance were used as the outcome indicators, and the methodological quality of the literatures was evaluated strictly. The extracted data were analyzed by RevMan 5.3 and Stata 14 software. Results: A total of 20 randomized controlled studies were included, the overall quality of which was relatively high. No publication bias was found. There was no significant difference in nasal symptom scores, VAS scores and compliance between SCIT and SLIT (SMD value was 0.03, 0.14, respectively, RR=1.12; 95%CI value was -0.17-0.23, -0.03-0.31, 0.92-1.35, respectively, all P>0.05); SLIT group resulted in lower overall incidence of adverse reactions than that of SCIT group (RR=1.79, 95%CI: 1.42-2.26, P<0.05). Conclusion Both SCIT and SLIT have similar eppecacy and compliance for treatment of AR, while adverse reactions are more frequently observed in SCIT.