Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme that plays a crucial role in the development and progression of diabetes and its complications. Studies have reported that increased HDAC3 activity is associated with pancreatic β-cell dysfunction in type 1 diabetes, while in type 2 diabetes, HDAC3 affects insulin resistance and signaling by regulating the metabolism of the liver, adipose tissue, and muscle. Additionally, HDAC3 plays a key role in diabetic complications such as cardiomyopathy, retinopathy, and nephropathy. Selective inhibition of HDAC3 has the potential to improve insulin sensitivity, reduce chronic inflammation, and enhance pancreatic cell function, offering a promising new therapeutic strategy for diabetes and its complications.

OBJECTIVE: To analyze the clinical efficacy of manual reduction combined with 3D printing small splint external fixation and synchronous manual reduction combined with traditional small splint external fixation in the treatment of humeral shaft. METHODS: Between January 2021 and December 2022, 40 patients with humeral shaft fractures were treated with 3D printing small splints and traditional small splints. They were divided into 3D group and traditional group according to different fixation methods. Among them, there were 15 males and 5 females in the 3D group, aged from 20 to 52 years old with an average of (36.3±15.6) years old. In the traditional group there were 17 males and 3 females, aged from16 to 51 years old with an average of (32.9±17.2) years old. The occurrence of complications, duration of fracture healing, rate of fracture healing, subjective evaluation scores for brace comfort at 1 week and 4 weeks, as well as the Constant-Murley shoulder function score and Mayo elbow function score at 8 weeks and 16 weeks were compared between the two groups. RESULTS: All patients were followed up for 16 weeks. The 3D group did not experience any complications, while there were two cases of complications in the traditional group. However, this difference was not found to be statistically significant (χ²=2.105, P=0.146). The fracture healing time of the 3D group (90.1±4.5) days was significantly shorter compared to that of the traditional group (93.3±3.8) days (P<0.05). The subjective evaluation scores for brace comfort in the 3D group (53.7±2.3) points and (62.8±1.1) points were significantly higher than those in the traditional group (45.6±2.4) points and (52.3±1.4) points at 1 and 4 weeks after reduction (P<0.05). After 8 weeks of reduction, the Constant-Murley shoulder function score in the 3D group was(68.1±5.3) points, which demonstrated a statistically significant improvement compared to the traditional group(54.3±4.9) points (P<0.05). However, at 16 weeks post-reduction, there were no significant differences observed between the two groups (P>0.05). The Mayo elbow function score of the 3D group (84.1±7.5) points was significantly superior to that of the traditional group (79.5±6.8) points at 8 weeks post-reduction (P<0.05). However, there was no statistically significant difference between the two groups at 16 weeks post-reduction (P>0.05). CONCLUSION For humeral shaft fractures with conservative treatment indications, manual reduction combined with 3D printed small splints is a good choice for treatment. The patient's comfort level is higher, which can not only reduce the occurrence of complications, but also improve the fracture healing rate and joint function to a certain extent, and improve the patient's quality of life.
Humans ; Female ; Male ; Adult ; Middle Aged ; Humeral Fractures/physiopathology* ; Printing, Three-Dimensional ; Splints ; Adolescent ; Young Adult ; Fracture Healing

OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective:To explore the difference between selective lobar bronchial block and main bronchial block in thoracoscopic surgery in children.Methods:A retrospective cohort study was conducted to analyze the clinical data of 150 children undergoing thoracoscopic surgery admitted to Henan Children's Hospital, Zhengzhou Children's Hospital, and Children's Hospital Affiliated to Zhengzhou University from December 2019 to December 2022. In the examination of the electronic medical record, 80 children were found to have selective lobar bronchial block, which was used as the study group, and 70 children were matched as the control group.Compare the general data of children in the two groups, such as age, gender, weight, surgical time, and other data. Compare the two groups with respect to hypoxemia, degree of pulmonary collapse, atelectasis, and number of bronchial blocker shifts. Compare the heart rate(HR), mean arterial pressure(MAP), degree of pulmonary collapse, and airway pressure(PAW) at different time points in the two groups[before single lung ventilation(OLV)(T1), 10 min after OLV(T2), and 10 min after OLV(T3)] Difference in alveolar arterial oxygen partial pressure(AaDO 2) levels. Results:Comparison of the incidence of hypoxemia, bronchial blocker displacement, and atelectasis in children in the study group were statistically significant( P<0.05). The results of repeated measurement of variance showed that there was statistically significant difference in the inter subject effects of HR and MAP levels at different time points between the two groups based on time factors( P<0.05). The results of repeated measurement of variance showed that there was statistical significance between the inter-subjective effects of the levels of PAW and AaDO 2 at different time points of the two groups with time factor as the source, group as the source, and intra-subjective effects with time and group interaction as the source( P<0.05). The levels of PAW and AaDO 2 in the study group at time points T2 and T3 were significantly lower than those in the control group, and the differences between the groups were statistically significant( P<0.05). Conclusion:The effect of selective lobobronchial blockade in thoracoscopic surgery in children is ideal, which can effectively improve the ventilation and related oxygenation of children, and reduce the occurrence of complications such as atelectasis and hypoxemia.

Objective To summarize the aortographic features of child patients with Kawasaki disease(KD)complicated by coronary artery lesion(CAL)who were treated at the Wuhan Children's Hospital of China.Methods The clinical data of 30 child patients with early recovery stage KD complicated by CAL,who received aortic angiography examination at Wuhan Children's Hospital of China between June 2016 and June 2023,were retrospectively analyzed.Preoperative echocardiography was adopted to evaluate the severity of CAL,and aortic angiography under laryngeal mask general anesthesia was performed.Results Successful aortic angiography examination was accomplished in all the 30 child patients with KD complicated by CAL.After angiography,the CAL risk classification results showed that grade I was seen in 5,grade Ⅱ in 7,grade Ⅲ in 12,grade Ⅲ in 4,and grade V in 2 child patients.Of all child patients,old coronary thrombosis was found in one(grade Ⅲb),and coronary artery stenosis with collateral circulation formation in one(grade Ⅴ).The CAL was located at the proximal segment(n=15),middle segment(n=3)and distal segment(n=2)of the right coronary artery,at the left main coronary artery(n=12),and at the proximal segment of left coronary artery anterior descending branch(n=9).Electrocardiography showed sinus rhythm(n=17),sinus arrhythmia(n=4),right bundle branch block(n=4),atrial premature beat(n=1),ventricular premature beat(n=2),T-wave change(n=1),and Q-wave change(n=1,coronary lesion grade V,echocardiography suggested left heart enlargement).No cardiac enlargement,cardiac functional insufficiency,or valvular regurgitation signs were observed in the remaining child patients.Conclusion It is clinically safe and feasible to perform aortic angiography examination in child patients with early recovery stage KD complicated by CAL.In this series of child patients with KD,CAL mainly occurs at the proximal segment of coronary artery,especially at the proximal segment of right coronary artery as well as at the left main artery and left anterior descending branch.

BACKGROUND:Early diagnosis and treatment of intervertebral disc degeneration is particularly important.Pyroptosis of nucleus pulposus cells plays an important role in the early process of intervertebral disc degeneration,but the role of pyroptosis-related molecules of nucleus pulposus cells in early intervertebral disc degeneration and related molecular markers are still unclear. OBJECTIVE:To explore the diagnostic and therapeutic value of differentially expressed genes related to pyroptosis during intervertebral disc degeneration. METHODS:Public datasets of the GEO database were integrated for differential analysis,and intersected with 33 pyroptosis-related genes previously reported.Using Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes,pathway enrichment analysis was performed in genes related to pyroptosis during intervertebral disc degeneration.Enrichment analysis of the intervertebral disc degeneration dataset was conducted using gene set enrichment analysis.To construct the immune cell spectrum in intervertebral disc degeneration samples,the correlation between the differentially expressed pyroptosis-related genes and immune cells was analyzed.Protein interaction networks were built.Screening of the Hub gene to identify key genes associated with intervertebral disc degeneration in protein interaction networks.The receiver operating characteristic curve of the differentially expressed pyroptosis-related genes was plotted,and the area under the curve was calculated.The clinical diagnostic value of target genes was explored.qRT-PCR was applied to verify the difference in the expression of pyroptosis-related genes between normal human nucleus pulposus cells and degenerated human nucleus pulposus cells with intervertebral discs. RESULTS AND CONCLUSION:(1)4426 differentially expressed genes associated with intervertebral disc degeneration were obtained,and 14 differentially expressed pyroptosis-related genes were obtained after the intersection.(2)Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed important enrichment pathways,mainly related to inflammation,cell cycle,infection and NOD-like receptor pathway.Gene set enrichment analysis showed that pathways such as amino acid metabolism and P53 transcription regulation were significantly enriched in patients with intervertebral disc degeneration.Immune infiltration analysis suggested that the occurrence and development of intervertebral disc degeneration were closely related to immune cells.(3)A total of five Hub genes were screened,namely IL1-β,Caspase-1,AIM2,Caspase-5,and NLRC4.(4)Acquisition and identification of key biomarkers for intervertebral disc degeneration:After intersecting the two datasets of GEO with the pyroptosis-related gene,it was found that NLRP3 had significant expression differences,and the receiver operating characteristic curve showed that NLRP3 had clinical diagnostic significance.(5)qRT-PCR showed that the expression of Hub genes such as IL1-β,Caspase-5 and NLRC4 was significantly increased in the nucleus pulposus cells of intervertebral disc degeneration(P<0.05),and there was no difference in Caspase-1,AIM2 and NLRP3 expression(P>0.05).(6)It is suggested that cell pyroptosis plays an important mechanism in the occurrence and development of intervertebral disc degeneration,among which pyroptosis-related molecules NLRP3,IL1-β,Caspase-5 and NLRC4 have early diagnosis and treatment value.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors.Methods:In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children′s Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors.Results:Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis ( HR=2.55, 95% CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant ( HR=2.96, 95% CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions:Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Objective To provide a longitudinal evaluation tool based on the frequency of aggressive be-havior for the aggression assessment of schizophrenia patients.Methods The Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version(LHA-CV)based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical insti-tution.The reliability of LHA-CV was analyzed by means of split-half reliability,test-retest reliability and inter-evaluator consistency.The validity was analyzed by item analysis,construct validity and crite-rion validity.Results Item analysis found that LHA-CV had good homogeneity and discriminant validity.Exploratory factor analysis found that the Kaiser-Meyer-Olkin(KMO)test value was 0.80,and the Bartlett's sphericity test χ2=1203.46(P<0.05),and it revealed four factors including non-physical ag-gression,physical aggression,self-directed aggression and antisocial behavior/consequences.The factor loadings for all 11 items were greater than 0.40.Confirmatory factor analysis was performed on the factor model,Chi-square degree of freedom(χ2/df)was 3.61,root mean square error of approxima-tion(RMSEA)was 0.07,goodness-of-fit index(GFI)was 0.92,comparative fit index(CFI)was 0.90,incremental fit index(IFI)was 0.90,and the discriminant validity of each factor was good.The criterion validity test showed the total score of LHA-CV was positively correlated with the aggressive behavior level of MacArthur Community Violence Instrument,the total score of Buss-Perry Aggression Scale,and the score of Antisocial Personality Disorder Subscale of Personality Diagnostic Question-naire-4th Edition Plus(PDQ-4+_ASPD,P<0.05).The Cronbach's α coefficient of non-physical aggres-sion,physical aggression,self-directed aggression,antisocial behavior/consequences and LHA-CV total score were 0.82,0.73,0.74,0.56 and 0.79,respectively.The test-retest reliability,Spearman-Brown split-half reliability and intra-class correlation coefficient of LHA-CV total score were 0.82(P<0.05),0.66 and 0.99,respectively.Conclusion LHA-CV has good reliability and validity,and can be used as an evaluation tool for longitudinally assessing aggressive behavior in schizophrenia patients.

Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were＞50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P＜0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P＜0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P＜0.001).IgG index was positively correlated with ISR(r=0.878,P＜0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.