ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

Objective To investigate the clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.

Background Bipolar disorder is a severe mental disorder characterized by cycling between mania/hypomania and depression,yet its underlying pathophysiological mechanism remains unclear.Several prior studies have suggested a potential role for voltage-gated calcium channel subunit genes in the etiology of bipolar disorder,particularly in their influence on brain structure.Objective To investigate the differences in grey matter volume(GMV)for individuals with bipolar disorder compared to healthy controls,and to explore the potential influence of calcium channel voltage-dependent T-type α1 G subunit(CACNA1G)rs757415 polymorphism on GMV in bipolar disorder and clarify the specific brain regions associated with this genetic variation,thus offering a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder.Methods A cohort of 289 patients who met the Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-IV)criteria for bipolar disorder were selected for participation.These patients were either admitted to hospital or examined in outpatient clinic for bipolar disorder at the Mental Health Center of West China Hospital,Sichuan University between September 2013 and December 2022.Another 322 healthy individuals were concurrently recruited as a control group from Sichuan University and surrounding communities.All participants underwent brain imaging using a 3.0 T magnetic resonance scanner to acquire data on GMV.Additionally,the presence of the CACNA1G rs757415 polymorphism was validated using the imLDRTM technique.Spearman correlation analysis was utilized to investigate potential relationship between abnormal brain regions identified through GMV data and clinical characteristics of the patients.Then the genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed using the full factor method.Results The study successfully enrolled 173 patients with bipolar disorder and 207 healthy controls who completed all the necessary procedures.Analyses revealed decreased GMV for patients with bipolar disorder compared to healthy controls in the left cerebellar declive extending to cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus and inferior occipital gyrus(t=5.664,P<0.05);in the right cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus extending to lingual gyrus(t=4.583,P<0.05);in the bilateral anterior cingulate/paracingulate gyri,superior frontal gyrus and precuneus(t=7.543,P<0.05);in the left lingual gyrus and superior temporal gyrus(t=6.593,P<0.05);and in the right insula entending to central operculum(t=7.153,P<0.05).Correlation analysis indicated that the duration of bipolar disorder was positively correlated with cerebrospinal fluid volume(r=0.258,P=0.003),whereas negatively correlated with the GMV in the left cerebellar declive extending to cerebellar anterior/posterior lobe,inferior occipital gyrus and parahippocampal gyrus(r=-0.204,P=0.019),in the right cerebellar anterior lobe extending to right cerebellar posterior lobe,fusiform gyrus,parahippocampal gyrus and lingual gyrus(r=-0.238,P=0.006),in the bilateral superior frontal gyrus extending to anterior cingulate/paracingulate gyri and precuneus(r=-0.219,P=0.012),in the left lingual gyrus extending to superior temporal gyrus(r=-0.296,P=0.001),and in the right insula extending to central operculum(r=-0.257,P=0.003).A significant genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5(F=19.967,P<0.05).In the control group,individuals carrying the non-risk allele showed increased GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 compared to those carrying the risk allele.In contrast,within the patient group,risk allele carriers exhibited increased GMV in the same brain regions when compared to non-risk allele carriers.Moreover,the GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 of patients with bipolar disorder carrying risk alleles was increased compared to healthy controls.Conclusion CACNA1G rs757415 polymorphism may affect the GMV in the right parahippocampal gyrus,fusiform gyrus and cerebellum 4/5 of patients with bipolar disorder.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To analyze the incidence of venous thromboembolism(VTE)in pulmonary patients and explore the assessment and prevention of the risk of pneumonia accompanied VTE.Methods The patients with pneumonia were divided into control group(simple pneumonia)and treatment group(with VTE)according to the condition of VTE.Demographic data,blood routine,coagulation index,liver and kidney function index and blood gas index were collected.Statistical methods like chi square test,t-test and nonparametric rank sum test were applied to compare the differences between the two groups.Finally,the nomogram was established according to the logistic regression results and the receiver operating characteristic(ROC)curve was calculated.Results 106 cases in control group and 29 cases in treatment group.Univariate analysis showed that age,D-dimer,fibrinogen degradation products,white blood cell count,neutrophil count,albumin-globulin ratio were statistically significant(P＜0.05).Multivariate logistic regression analysis suggests that age[odds ratio(OR)=1.052],D-dimer(OR=2.339),and albumin/globulin(OR=0.042)are independent affecting factors for VTE in pneumonia patients.A nomogram was developed and ROC was calculated,the area under curve(AUC)was 0.754.Conclusion High age,elevated D-dimer and decreased albumin/globulin are independent risk factors for VTE in pneumonia patients.More over,the established prediction model has good accuracy.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus(hsPDA).Methods A retrospective collection of clinical data was conducted on preterm infants with a gestational age of＜34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology,Maternal and Child Health Hospital of Hubei Province,Tongji Medical College,Huazhong University of Science and Technology,from January 2018 to June 2023.The subjects were divided into two groups based on the treatment approach:the ibuprofen group(95 cases)and the ibuprofen plus surgery group(44 cases).The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis.Results The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus,a resistance index(RI)value of the middle cerebral artery ≥0.80,and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA(P＜0.05).Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter＞2.85 mm,a middle cerebral artery RI value ≥0.80,and a total invasive mechanical ventilation time＞16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA(P＜0.05).The combined predictive value of these three factors was the highest,with an area under the curve of 0.843,a sensitivity of 86.5％,and a specificity of 75.0％(P＜0.05).Conclusions A ductus arteriosus diameter＞2.85 mm,a middle cerebral artery RI value ≥0.80,and a total invasive mechanical ventilation time＞16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA,and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.[Chinese Journal of Contemporary Pediatrics,2024,26(4):343-349]

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

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.