ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Objective:To investigate the clinical characteristics,coexisting gene mutations and prognosis of acute myeloid leukemia(AML)patients with GATA2 gene mutation.Methods:The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively,the next-generation sequencing technology was used to detect the mutated genes in those patients.The clinical characteristics of AML patients with GATA2 mutations,the co-mutated genes of GATA2 mutations,and the effect of GATA2 mutation on prognosis were analyzed.Results:A total of 23 patients(6.2％)with GATA2 mutation was detected in 370 AML patients.Compared with GATA2 non-mutation group,patients in GATA2 mutation group were mostly normal karyotypes(P=0.037)and in low-risk cytogenetic stratification(P=0.028).The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group(P=0.010,P=0.009).There were no statistically significant differences between the two groups in terms of sex,age,white blood cell count(WBC),platelet count,hemoglobin,bone marrow(BM)blast,induction chemotherapy regimen and CR rate(P＞0.05).Among the 23 patients with GATA2 mutation,the most common co-mutated genes were CEBPAdm,NRAS(both 39.1％),NPM1,FLT3,TET2,WT1(all 17.4％),ASXL1 and IDH1(both 13.0％).Survival analysis showed that there was no statistical difference in 5-year overall survival(OS)and leukemia-free survival(LFS)rates between patients with and without GATA2 mutations in whole cohort(n=370)(P=0.306,P=0.308).Among 306 patients without CEBPAdm,the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group,but the difference was not statistically significant(P=0.092,P=0.056).Among 64 patients with CEBPAdm,there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group(P=0.104),but the 5-year LFS rate of the GATA2 mutation group was significantly decreased(P=0.047).Among the 23 patients with GATA2 mutation,16 cases received the"3+7"induction regimen,of which 12 cases received allogeneic hematopoietic stem cell transplantation(allo-HSCT);7 cases received the"DCAG"induction regimen,of which 3 cases received allo-HSCT.The CR rate was not statistically different between the"3+7"regimen group and the"DCAG"regimen group(P=1.000).The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group(P=0.021,P=0.020).Conclusion:GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification,and it is significantly associated with CEBPAdm and NRAS co-mutations.The prognostic significance of GATA2 is influenced by CEBPAdm.The choice of"3+7"or"DCAG"induction regimen in patients with GATA2 mutation does not affect their CR rate,while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

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.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ² test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.
Infant ; Male ; Infant, Newborn ; Humans ; Pregnancy ; Female ; Bronchopulmonary Dysplasia/epidemiology* ; Infant, Premature ; Hypertension, Pulmonary/epidemiology* ; Retrospective Studies ; Nomograms ; Ductus Arteriosus, Patent/epidemiology* ; Pneumonia, Ventilator-Associated/complications* ; Cesarean Section/adverse effects* ; Gestational Age ; Risk Factors ; Sepsis

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates