The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective:To evaluate the therapeutic efficacy of an upper limb rehabilitation robot on the recovery of elbow function recovery following arthroscopic elbow joint release.Methods:Seventy-two patients who underwent arthroscopic elbow joint release at Shanghai Sixth People’s Hospital from December 2022 to December 2023 were recruited. All patients were randomly assigned to either the conventional group (n=36; 16 males, 20 females; age 34.39±9.04 years, range 24-56; fractures: 4 intercondylar humerus, 18 olecranon, 8 radial head, 6 other) which received conventional rehabilitation postoperatively, or the robot-assisted group (n=36; 18 males, 18 females; age 33.78±9.98 years, range 20-59; fractures distribution identical to the conventional group) receiving conventional rehabilitation combined with robot-assisted upper limb rehabilitation therapy. The active range of motion (ROM) of elbow joint, Mayo elbow performance score (MEPS), visual analogue scale (VAS) of elbow joint were recorded preoperatively and at 4 weeks and 3 months postoperatively. The surface electromyography were analyzed at 3 months postoperatively.Results:All patients completed the 3-month rehabilitation program. At 4 weeks postoperatively, the conventional group exhibited a mean active ROM of 106.78°±9.91°, MEPS of 67.78±7.68, VAS of 2.11±0.74; the robot-assisted group showed active ROM of 113.72°±7.06°, MEPS of 73.33±9.28, VAS of 21.89±0.46. By 3 months postoperatively, the conventional group achieved a mean active ROM of 118.11°±6.75°, MEPS of 85.00±8.66, VAS of 0.67±0.67; robot-assisted achieved a mean active ROM of 127.61°±6.61°, MEPS of 91.11±6.57, VAS of 0.39±0.49. Both groups exhibited significant improvements in active ROM and MEPS, and significant reductions in VAS scores at 4 weeks and 3 months postoperatively compared with preoperatively values ( P<0.05). The robot-assisted group demonstrated significantly higher active ROM and MEPS at both 4 weeks and 3 months postoperatively, and a significantly lower VAS score at 3 months postoperatively, compared with the conventional group ( P<0.05). Surface electromyography at 3 months revealed significantly higher biceps brachii root mean square and significantly lower co-contraction index in the robot-assisted group compared to the conventional group ( P<0.05). No adverse symptoms were reported in the treated elbows of either group during the operation and follow-up period. Conclusion:The integration of upper limb rehabilitation robot-assisted therapy and conventional rehabilitation program significantly enhances the recovery of elbow range of motion and functional outcomes at 3 months following arthroscopic elbow joint release.

ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal （ULN） of alanine aminotransferase （ALT） in evaluating significant liver pathological injury in patients with chronic hepatitis B virus （HBV） infection， and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination， and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA （>30 IU/mL）. According to the treatment threshold or ULN of ALT， the patients were divided into group 1 with 575 patients （≤35 U/L for male patients， ≤25 U/L for female patients）， group 2 with 430 patients （≤30 U/L for male patients， ≤19 U/L for female patients）， group 3 with 443 patients （≤27 U/L for male patients， ≤24 U/L for female patients）， group 4 with 446 patients （≤25 U/L）， group 5 with 158 patients （>35 U/L for male patients， >25 U/L for female patients）， and group 6 with 145 patients （>30 — ≤35 U/L for male patients， >19 — ≤25 U/L for female patients）. Groups 2， 5， and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury， and groups 1， 2， 3， and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade （G）， liver fibrosis stage （S）， and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis （forward stepwise） was performed with whether liver pathology met the treatment indication （≥G2 and/or ≥S2） as the dependent variable and related factors with a significant impact on the dependent variable （P <0.05） as the independent variable. The receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC）， as well as sensitivity， specificity， positive predictive value， negative predictive value， positive likelihood ratio， and negative likelihood ratio， was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients， 259 （35.33%） had ≥G2 liver inflammation， 211 （28.79%） had ≥S2 liver fibrosis， and 306 （41.75%） had treatment indication （≥G2 and/or ≥S2）. There was a significant difference in liver inflammation grade （G0 — G4） between groups 2， 5， and 6 （χ²=22.869， P <0.001）， and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups （χ²=21.742 and 14.921， P<0.001 and P=0.001）. There was a significant difference in liver fibrosis stage （S0 — S4） between groups 2， 5， and 6 （χ²=16.565， P<0.001）， and there were also significant differences in the constituent ratios of patients with ≥S2， ≥S3 or S4 liver fibrosis between the three groups （χ²=13.264， 13.050， and 6.260， P=0.001， 0.001， and 0.044）. There were significant differences between groups 2， 5， and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology （χ²=20.728， P<0.001）. There were significant differences between groups 2， 5， and 6 in the constituent ratio of male patients （χ²=24.836， P<0.05）， age （F=5.710， P<0.05）， ALT （F=473.193， P<0.05）， aspartate aminotransferase （AST） （F=107.774， P<0.05）， ALT/AST ratio （F=40.167， P<0.05）， γ-glutamyl transpeptidase （GGT） （H=15.463， P<0.05）， aspartate aminotransferase-to-platelet ratio index （APRI） （H=63.024， P<0.05）， and LIF-5 （5 indicators for liver inflammation and fibrosis） （H=46.397， P<0.05）. In groups 1 — 4， compared with the patients without treatment indication， the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg， significantly lower levels of platelet count （PLT） and HBV DNA， and significantly higher age， ALT， AST， GGT， APRI， FIB-4， and LIF-5 （all P<0.05）. The Logistic regression analysis showed that age （odds ratio ［OR］=1.044， 95% confidence interval ［CI］： 1.025 — 1.063， P<0.001）， GGT （OR=1.022， 95%CI： 1.007 — 1.038， P=0.003）， and HBV DNA （OR=0.839， 95%CI： 0.765 — 0.919， P<0.001） were influencing factors for treatment indication based on liver pathology in group 1； HBeAg （OR=1.978， 95%CI： 1.269 — 3.082， P=0.003）， age （OR=1.048， 95%CI： 1.025 — 1.071， P<0.001）， GGT （OR=1.016， 95%CI： 1.001 — 1.031， P=0.041）， and PLT （OR=0.995， 95%CI： 0.991 — 1.000， P=0.049） were influencing factors in group 2； age （OR=1.040， 95%CI： 1.014 — 1.066， P=0.002）， ALT （OR=1.047， 95%CI： 1.005 — 1.092， P=0.029）， HBV DNA （OR=0.817， 95%CI： 0.736 — 0.907， P<0.001）， and LIF-5 （OR=7.382， 95%CI： 1.151 — 47.330， P=0.035） were influencing factors in group 3； age （OR=1.054， 95%CI： 1.031 — 1.077， P<0.001）， ALT （OR=1.061， 95%CI： 1.016 — 1.107， P=0.008）， and HBV DNA （OR=0.825， 95%CI： 0.743 — 0.917， P<0.001） were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation， ≥S2 liver fibrosis， and treatment indication in groups 1 — 4 had an AUC of >0.7； group 1 showed the lowest sensitivity （28.76%） and the highest specificity， positive predictive value， positive likelihood ratio， and negative likelihood ratio in judging treatment indication； group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio； groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level， the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment （with a higher specificity）， while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment （with a higher sensitivity）.

Objective:To investigate the efficacy of volar anatomical locking plates combined with dorsal mini-plates in treating com-plex distal radius fractures.Methods:We retrospectively included patients with complex distal radius fractures who had been treated with volar locking plates and dorsal mini-plates at Chongqing General Hospital from January 2019 to June 2023.The quality of articu-lar surface fragment reduction was assessed through image analysis.Follow-up data included the Mayo wrist score,Disabilities of the Arm,Shoulder,and Hand Questionnaire(DASH)score,wrist range of motion,time to fracture healing,and complications.Results:Twenty-eight patients[19 males,9 females;mean age,(45.4±11.9)years]were included,with a mean follow-up of 1(4.9±3.6)months.Their injury mechanisms included falls from height(11 cases),traffic accidents(9 cases),and simple falls(8 cases).After op-eration,the volar tilt was(5.1±4.9)°,and the ulnar inclination was(19.8±2.8)°;at the final follow-up,the angles were(5.2±4.8)° and(19.3±2.5)°,respectively,neither showing any significant change(P>0.05).At the final follow-up,all fractures healed,with a mean healing time of 3.6 months.At 1 year after operation,the wrist extension was(50.7±6.3)°;the wrist flexion was(49.4±6.1)°;the DASH score was 15.0±6.3;the Mayo wrist scores were excellent or good in 24 cases;the grip strength of the affected side averaged 84.4%of that of the contralateral side.No implant loosening occurred.Two cases of superficial wound infection and one case of exten-sor tendon irritation were reported.Conclusion:Locked volar plat-ing combined with dorsal mini-plating provides stable fixation for comminuted articular surface fragments in complex distal radius fractures,enabling early functional rehabilitation with favorable wrist recovery and low rates of dorsal tendon irritation.

Objective To investigate the clinical value of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy.Methods The clinical data of 6 patients with esophageal stricture lesions with EUS-FNA that cannot be clearly diagnosed by endoscopic general biopsy from January 2021 to Jun 2023 were retrospectively analyzed,and the accuracy of EUS-FNA was analyzed for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy,while the results of surgery pathology or final follow-up results was taken as the diagnostic criteria.Results All the patients underwent EUS-FNA.The puncture clearly diagnosed 5 cases of malignancy and 1 case of chronic inflammation.Among them,5 patients underwent surgical operations,and the postoperative pathological findings were consistent with the puncture pathology.One patient was followed up for a long time and had repeated gastroscopy.There was no evidence of malignant tumor in the clinical manifestations and routine gastroscopic findings,so it was still considered to be an inflammatory change,which was consistent with the puncture pathological result.All patients had no complications,including abdominal pain,bleeding,perforation,and infection.Conclusion EUS-FNA is an effective and safe method for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy and has high clinical application value.

Objective Evaluation of the off-label use of flupentixol melitracen based on an evidence-based medicine approach and recommendations for graded management.Methods The off-label prescriptions of flupentixol melitracen for outpatient clinics in our hospital from November 1,2023,to October 31,2024,were collected to count the clinical diagnoses of off-label use of flupentixol melitracen tablets.Searching foreign drug manuals,authoritative medical monographs,as well as guidelines and literature databases such as the US National Guidelines Clearinghouse(NGC),Guidelines International Network(GIN),Medlive,Yaozh.com,PubMed,Cochrane Library,Embase,WanFang Data,VIP,CNKI and other guidelines and literature databases,to collect literature on evidence-based medical evidence related to the flupentixol melitracen tablets for off-label use.The literature was screened according to the pre-established inclusion and exclusion criteria,and the quality of evidence was assessed and graded to determine the evidence of evidence-based medicine for off-label use,and to make recommendations for grading management.Results Flupentixol melitracen tablets off-label use involves 13 clinical diagnoses of gastritis,sleep disorders,dizziness,neurological disorders,gastroesophageal reflux,gastrointestinal disorders,headache(tension-type headache),abdominal pain(functional abdominal pain syndrome),palpitations,constipation,neurasthenia,cardiac neurosis,and neuralgia.A total of 8 evidence-based medical literature related to off-label use were included,including 4 guidelines,1 Meta-analysis,and 3 clinical randomised controlled trials(RCTs).Based on the evaluation of evidence-based medicine methodology,the quality grade of a Meta-analysis was extremely low,and 3 RCTs were at high risk of bias.There was evidence-based medical evidence for the determination of treating chronic gastritis,which is recommende as level A management and agreed to be used.There was evidence-based medical evidence for the adjudication of treating sleep disorders,headache(tension-type headache),abdominal pain(functional abdominal pain syndrome),neuralgia,and chronic constipation,which was recommended as level B management and restriction for use.There was no evidence-based medical evidence for the remaining off-label uses of the drug.Conclusion The evidence-based medicine evidence for flupentixol melitracen in the treatment of chronic gastritis,sleep disorders,headache,abdominal pain,neuralgia,and chronic constipation are relatively sufficient and their use are reasonable,while the rationale for other off-label use are relatively low and are recommended to be contraindicated.Through the evidence-based medicine methods,the evaluation system for off-label use of flupentixol melitracen has been improved,providing a basis for rational clinical medication and ensuring the safety of patients' medication.

Objective:To evaluate the therapeutic efficacy of an upper limb rehabilitation robot on the recovery of elbow function recovery following arthroscopic elbow joint release.Methods:Seventy-two patients who underwent arthroscopic elbow joint release at Shanghai Sixth People’s Hospital from December 2022 to December 2023 were recruited. All patients were randomly assigned to either the conventional group (n=36; 16 males, 20 females; age 34.39±9.04 years, range 24-56; fractures: 4 intercondylar humerus, 18 olecranon, 8 radial head, 6 other) which received conventional rehabilitation postoperatively, or the robot-assisted group (n=36; 18 males, 18 females; age 33.78±9.98 years, range 20-59; fractures distribution identical to the conventional group) receiving conventional rehabilitation combined with robot-assisted upper limb rehabilitation therapy. The active range of motion (ROM) of elbow joint, Mayo elbow performance score (MEPS), visual analogue scale (VAS) of elbow joint were recorded preoperatively and at 4 weeks and 3 months postoperatively. The surface electromyography were analyzed at 3 months postoperatively.Results:All patients completed the 3-month rehabilitation program. At 4 weeks postoperatively, the conventional group exhibited a mean active ROM of 106.78°±9.91°, MEPS of 67.78±7.68, VAS of 2.11±0.74; the robot-assisted group showed active ROM of 113.72°±7.06°, MEPS of 73.33±9.28, VAS of 21.89±0.46. By 3 months postoperatively, the conventional group achieved a mean active ROM of 118.11°±6.75°, MEPS of 85.00±8.66, VAS of 0.67±0.67; robot-assisted achieved a mean active ROM of 127.61°±6.61°, MEPS of 91.11±6.57, VAS of 0.39±0.49. Both groups exhibited significant improvements in active ROM and MEPS, and significant reductions in VAS scores at 4 weeks and 3 months postoperatively compared with preoperatively values ( P<0.05). The robot-assisted group demonstrated significantly higher active ROM and MEPS at both 4 weeks and 3 months postoperatively, and a significantly lower VAS score at 3 months postoperatively, compared with the conventional group ( P<0.05). Surface electromyography at 3 months revealed significantly higher biceps brachii root mean square and significantly lower co-contraction index in the robot-assisted group compared to the conventional group ( P<0.05). No adverse symptoms were reported in the treated elbows of either group during the operation and follow-up period. Conclusion:The integration of upper limb rehabilitation robot-assisted therapy and conventional rehabilitation program significantly enhances the recovery of elbow range of motion and functional outcomes at 3 months following arthroscopic elbow joint release.

Objective Evaluation of the off-label use of flupentixol melitracen based on an evidence-based medicine approach and recommendations for graded management.Methods The off-label prescriptions of flupentixol melitracen for outpatient clinics in our hospital from November 1,2023,to October 31,2024,were collected to count the clinical diagnoses of off-label use of flupentixol melitracen tablets.Searching foreign drug manuals,authoritative medical monographs,as well as guidelines and literature databases such as the US National Guidelines Clearinghouse(NGC),Guidelines International Network(GIN),Medlive,Yaozh.com,PubMed,Cochrane Library,Embase,WanFang Data,VIP,CNKI and other guidelines and literature databases,to collect literature on evidence-based medical evidence related to the flupentixol melitracen tablets for off-label use.The literature was screened according to the pre-established inclusion and exclusion criteria,and the quality of evidence was assessed and graded to determine the evidence of evidence-based medicine for off-label use,and to make recommendations for grading management.Results Flupentixol melitracen tablets off-label use involves 13 clinical diagnoses of gastritis,sleep disorders,dizziness,neurological disorders,gastroesophageal reflux,gastrointestinal disorders,headache(tension-type headache),abdominal pain(functional abdominal pain syndrome),palpitations,constipation,neurasthenia,cardiac neurosis,and neuralgia.A total of 8 evidence-based medical literature related to off-label use were included,including 4 guidelines,1 Meta-analysis,and 3 clinical randomised controlled trials(RCTs).Based on the evaluation of evidence-based medicine methodology,the quality grade of a Meta-analysis was extremely low,and 3 RCTs were at high risk of bias.There was evidence-based medical evidence for the determination of treating chronic gastritis,which is recommende as level A management and agreed to be used.There was evidence-based medical evidence for the adjudication of treating sleep disorders,headache(tension-type headache),abdominal pain(functional abdominal pain syndrome),neuralgia,and chronic constipation,which was recommended as level B management and restriction for use.There was no evidence-based medical evidence for the remaining off-label uses of the drug.Conclusion The evidence-based medicine evidence for flupentixol melitracen in the treatment of chronic gastritis,sleep disorders,headache,abdominal pain,neuralgia,and chronic constipation are relatively sufficient and their use are reasonable,while the rationale for other off-label use are relatively low and are recommended to be contraindicated.Through the evidence-based medicine methods,the evaluation system for off-label use of flupentixol melitracen has been improved,providing a basis for rational clinical medication and ensuring the safety of patients' medication.

Objective To investigate the clinical value of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy.Methods The clinical data of 6 patients with esophageal stricture lesions with EUS-FNA that cannot be clearly diagnosed by endoscopic general biopsy from January 2021 to Jun 2023 were retrospectively analyzed,and the accuracy of EUS-FNA was analyzed for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy,while the results of surgery pathology or final follow-up results was taken as the diagnostic criteria.Results All the patients underwent EUS-FNA.The puncture clearly diagnosed 5 cases of malignancy and 1 case of chronic inflammation.Among them,5 patients underwent surgical operations,and the postoperative pathological findings were consistent with the puncture pathology.One patient was followed up for a long time and had repeated gastroscopy.There was no evidence of malignant tumor in the clinical manifestations and routine gastroscopic findings,so it was still considered to be an inflammatory change,which was consistent with the puncture pathological result.All patients had no complications,including abdominal pain,bleeding,perforation,and infection.Conclusion EUS-FNA is an effective and safe method for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy and has high clinical application value.

OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides(TSG)on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ(AngⅡ).METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups:control group,AngⅡgroup(2 μmol/L),TSG group(7.5 μg/mL),PFK-015 group[6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)inhibitor,10 nmol/L],and TSG+PFK-015 group(TSG 7.5 μg/mL+PFK-015 10 nmol/L).The surface area,protein synthesis,energy metabolism-related indicators[free fatty acid(FFA),coenzyme A(CoA),acetyl coenzyme A(acetyl-CoA)],and the expressions of glycolysis-related factors[hypoxia-inducible factor 1α(HIF-1α),glucose transporter protein 4(GLUT-4),lactate dehydrogenase A(LDHA),pyruvate dehydrogenase kinase 1(PDK1)and PFKFB3]in primary cardiomyocytes of each group were measured.RESULTS Compared with the control group,the surface area of primary cardiomyocytes and protein synthesis were significantly increased,the content of FFA,protein and mRNA expressions of HIF-1α,LDHA,PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group,while the contents of CoA and acetyl-CoA,the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated(P＜0.05).Compared with the AngⅡ group,both TSG group and PFK-015 group showed significant improvements in these indexes,with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone(P＜0.05).CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes,decrease protein synthesis,and inhibit their hypertrophic changes.These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.