ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Objective To analyze the adverse reaction reports （ADRs） of drug-induced liver injury in recent ten years, explore the characteristics and related rules of drug-induced liver injury, and provide reference for clinical safe drug use. Methods ADRs in our hospital from 2011 to 2021 which belonged to drug-induced liver injuries were collected, and Pareto analysis was carried on. Results In 259 ADR reports, the most common type of drug-induced liver injury was hepatocellular injury （37.84%）. The age of drug-induced liver injury was mainly over 46 years, totaling 195 （75.28%）. Drugs were mainly distributed in cardiovascular system medicine （44.02%）, anti-infective medicine （23.94%）and anti-tumor medicine （11.58%）. Among the cardiovascular drugs, atorvastatin calcium 40mg and over 40mg were the highest proportion, with 53 cases （46.49%）. The main anti-infectious drugs were cephalosporins （29.03%）, carbapenem （19.35%）， antifungal （17.74%）and quinolones （11.29%）. Adverse reactions occurred within 6 days （69.88%）, the duration of adverse reactions was 1-2 weeks （31.66%）, and most patients were improved （47.88%） or cured （37.07%）. Conclusion For middle-aged and elderly patients, when the application of cardiovascular system drugs, anti-infective drugs or anti-tumor drugs, it is necessary to monitor the liver function changes of patients for at least 6 days. If there are abnormalities, the drugs should be stopped or given treatment in time, to avoid the progress of drug-induced liver injury.

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Qinghao Biejiatang， first recorded in the Detailed Analysis of Warm Diseases （《温病条辨》） written by WU Jutong in the Qing Dynasty， is composed of Artemisiae Annuae Herba， Trionycis Carapax， Rehmanniae Radix， Anemarrhenae Rhizoma， and Moutan Cortex. With the effects of nourishing Yin and relieving heat， this prescription is often used to treat the syndrome of Yin deficiency and internal heat. The deficiency of healthy Qi， invasion of pathogenic toxins， loss of lung Yin， and generation of deficiency-heat are pathogenesis of lung cancer， pneumonia and other lung diseases， the treatment of which usually follows the principles of nourishing Yin， reinforcing healthy Qi， clearing lung， and eliminating heat. With the effects basically in accordance with the treatment principles of lung diseases， Qinghao Biejiatang is widely used in the treatment of lung diseases such as lung cancer-associated fever， hemoptysis or combined with bone metastasis， tuberculosis， community-acquired pneumonia， and pneumonia caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）. Basic experiments have shown that Qinghao Biejiatang may exert the therapeutic effects by reducing inflammation， maintaining immune balance， regulating intestinal flora， hormone secretion， lipid metabolism， and inhibiting tumor and oxidative damage. In addition， the main active ingredients of this prescription include artemisinin， luteolin， sitosterol， stigmasterol， polysaccharides， catalpol， paeoniflorin， quercetin， paeonol， gallic acid， timosaponin， and mangiferin， which have anti-tumor， anti-oxidant， anti-virus， inflammation-regulating， and immunomodulatory activities. The paper reviewed the clinical and basic studies of Qinghao Biejiatang in the treatment of lung diseases， aming to provide a theoretical basis for the clinical application.

Objective:To investigate the correlation between 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) and the inflammatory activation of polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) in acute myocardial infarction (AMI), and to evaluate the effect of intervention targeting PFKFB3 on the inflammatory activation of PMN-MDSC during AMI.Methods:① Clinical trial section: a observational study was conducted. The patients with acute coronary syndrome (ACS) admitted to Zhenjiang Fourth People's Hospital were enrolled, and they were divided into AMI group and non-AMI group according to clinical diagnosis. The peripheral venous blood of the two groups was collected to detect the proportion of PMN-MDSC, and the expression of PFKFB3 gene in mononuclear cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). ② Basic experiment section: a total of 30 male C57 mice (aged 6-8 weeks) were divided into normal control group ( n = 5), Sham group ( n = 5), AMI model group ( n = 10) and PFKFB3 inhibitor PKF-15 intervention group ( n = 10) according to random number table method. The AMI model of mice was reproduced by left anterior descending coronary artery (LADCA) ligation, and the mice in the Sham group did not attach the artery after thoracotomy. The PKF-15 intervention group was intraperitoneally injected with PKF-15 (20 μg/g) at the same time of LADCA ligation. Normal control mice did not receive any treatment. Peripheral venous blood and myocardial tissue of mice were collected 24 hours after modeling. Both the circulating PMN-MDSC ratio and the infiltration of PMN-MDSC in myocardial tissue were detected. After staining with hematoxylin-eosin (HE), the degree of inflammatory damage in mouse myocardial tissue was observed under light microscopy. PMN-MDSC were isolated from mice with flow cytometry, and the gene expressions of PFKFB3 and inflammatory factors were measured by RT-qPCR. Results:① Clinical trial section: the circulating PMN-MDSC ratio of patients in the AMI group ( n = 25) was significantly higher than that in the non-AMI group [ n = 20; (8.53±0.96)% vs. (1.13±0.39)%, P < 0.01], and PFKFB3 gene expression in the peripheral blood mononuclear cells was also increased (2 -ΔΔCt: 1.18±0.19 vs. 0.96±0.16, P < 0.01). Pearson correlation analysis showed that circulating PMN-MDSC ratio was positively correlated with PFKFB3 gene expression in mononuclear cells in AMI patients ( r = 0.608, P = 0.001). ② Basic experimental section: the circulating PMN-MDSC ratio and the infiltration of PMN-MDSC in myocardial tissue of AMI mice were significantly higher than those in the normal control group and Sham group. PFK-15 intervention could reduce the ratio of PMN-MDSC in the peripheral blood and myocardial tissue of AMI mice [(26.33±5.27)% vs. (75.12±5.02)% in peripheral blood, (20.87±2.97)% vs. (35.28±4.36)% in myocardial tissue, both P < 0.01]. Under light microscopy, the myocardial cells in the AMI modal group were disordered and a large number of inflammatory cells infiltrated. PFK-15 intervention could maintain a normal arrangement of cardiomyocytes and reduce the infiltration of inflammatory cells. The gene expression levels of PFKFB3 in the peripheral blood and myocardial tissue as well as the inflammatory factors in the myocardial tissue of AMI mice were significantly higher than those in the normal control group and Sham group. PKF-15 intervention could effectively reduce the gene expression levels of PFKFB3 in the peripheral blood and myocardial tissue as well as the inflammatory factors in the myocardial tissue of AMI mice [PFKFB3 mRNA (2 -ΔΔCt): 1.01±0.09 vs. 1.40±0.12 in peripheral blood, 0.95±0.09 vs. 1.47±0.10 in myocardial tissue; myocardial tissue tumor necrosis factor-α (TNF-α) mRNA (2 -ΔΔCt) was 14.55±3.99 vs. 29.66±3.90, interleukin-1β (IL-1β) mRNA (2 -ΔΔCt) was 8.72±1.35 vs. 18.53±2.43, IL-6 mRNA (2 -ΔΔCt) was 11.87±2.97 vs. 19.82±4.32, all P < 0.01]. Conclusions:The activation of PFKFB3 is closely related to the inflammatory activation of PMN-MDSC during AMI. Inhibition of PFKFB3 activity can inhibit the inflammatory activation of PMN-MDSC and reduce myocardial inflammatory injury.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Objective To analyze serum characteristics and determine the reference range for thyroid function among healthy 11～16 year-old teenagers in Xi'an in order to offer a theoretical basis for clinical diagnosis and therapy.Methods A sum of 1 378 healthy 11～16 year-old teenagers who met the inclusion criteria from the First Affiliated Hospital of the Air Force Medical University(Xijing Hospital)between January 2020 and December 2022 were selected as research subjects,including 628 males and 750 females.They were divided into three groups based on age:Group 1:11～＜13 year-olds(433 cases),Group 2:13～＜15 year-olds(425 cases),and Group 3:15～≤16 year-olds(520 cases).Differences in serum thyroid function indices among different genders and age groups were analyzed,the reference ranges for these indices were established,and 99 healthy 11-16 year-old teenagers who met the inclusion criteria were chosen for verification.Results There were no significant differences between different genders in thyroid stimulating hormone[TSH,2.56(1.80,3.63)μIU/ml vs 2.43(1.68,3.48)μIU/ml]and total thyroxine[TT4,97.84(85.34,111.00)nmol/L vs 98.20(87.16,111.23)nmol/L],the differences were statistically significant(Z=-1.881,-0.638,all P＞0.05).Meanwhile,the differences in free thyroxine[FT4,16.93(15.49,18.60)pmol/L vs 16.26(14.80,17.83)pmol/L],free triiodothyronine[FT3,6.21(5.66,6.80)pmol/L vs 5.59(4.98,6.19)pmol/L],and total triiodothyronine[TT3,2.24(1.96,2.55)nmol/L vs 2.04(1.78,2.34)nmol/L]between different genders were significant(Z=-5.368,-11.994,-6.417 all P＜0.01).The differences in thyroid function indices were significant among different age groups(Z=10.649～261.003,all P＜0.05).The reference ranges for thyroid function indices across different age groups and genders were established,in which thyroid function indicators were verified to be within the established reference range by 99 samples.Conclusion Teenage hormone secretion varies greatly,and the secretion of thyroid hormones is influenced by various factors.Thus,the diagnosis and treatment of teenage thyroid diseases cannot fully rely on the reference ranges provided by adults or manufacturers.This study established the reference range of the thyroid function indices of 11～16 year-old teenagers in Xi'an,offering clinical doctors'diagnosis and treatment data support.

Objective:To explore the relationship between body composition and the risk of gestational diabe-tes mellitus(GDM)in pregnant women.Methods:90 pregnant women with spontaneous pregnancy of singleton who underwent routine prenatal examination in our hospital were selected as GDM group,and 219 pregnant women with normal singleton in the same period as control group(NGT).The body composition was determined by bioimpedance method at 24-28 weeks of gestation.The relationship between body mass index(BMI),per-centage of body fat(FMP),percentage of fat-free body weight(FFMP),extracellular/intracellular fluid(ECW/ICW),body fat index(FMI)and GDM were analyzed.The levels of circulating adiponectin,fatty acid binding pro-tein 4(FABP4),leptin and fasting insulin(FINS)were measured by enzyme linked immunosorbent assay(ELISA)method,and their relationship with various indicators of human body composition was analyzed.Results:①Adi-ponectin in GDM group was lower than that in NGT group,while leptin was higher than that in control group(P＜0.05).②The FMP,ECW/ICW and FMI in GDM group were significantly higher than those in control group(P＜0.05).Univariate regression analysis showed that BMI,FMP,FMI and ECW/ICW before pregnancy were the risk factorsof GDM(OR＞1,P＜0.05),FFMP,MP,PP and M/F was the protective factor of GDM(OR＜1,P＜0.05).Multivariate analysis showed that only FMP was significantly correlated with the risk of GDM,which was an independent risk factor(OR＞1,P＜0.05).③In GDM group,HOMA-IR was positively correlated with FMI(r＞1,P＜0.05)and negatively correlated with PP(r＜1,P＜0.05).④The ROC curve showed that the diagnostic value of pre-pregnancy BMI、FMP、ECW/ICW and FMI in GDM was similar.There was no significant difference in pre-pregnancy BMI,FMP and FMI(P＞0.05),but they were slightly better than ECW/ICW(P＜0.001).Conclu-sions:Body composition during pregnancy is related to the risk of gestational diabetes.The increase in FMP is associated with an increased risk of developing GDM.The higher the FMP,the higher the risk of GDM.The diag nostic efficacy of BMI,FMP and FMI in GDM is Similar.