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 establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

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.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective:To explore the screening value of platelet parameters from blood cell analysis for MYH9-related disorders(MYH9-RD).Methods:A cross-sectional study was conducted with 38 patients diagnosed with MYH9-RD at Shenzhen Children's Hospital from May 1, 2016, to August 31, 2024, including 24 males and 14 females; the median age was 11.5 (3.8, 35) years; categorized by gene mutation location into "head region" ( n=8 ) and "tail region" ( n=30); and by clinical manifestations into " isolated hematological manifestations" ( n=16) and "hematological manifestations with extra-hematological involvement"( n=22). The control groups included 39 cases of immune thrombocytopenia (ITP), 38 cases of acute lymphoblastic leukemia (ALL), and 40 healthy individuals. Platelet-related parameters were detected by hematology analyzer, and platelet counts and sizes were confirmed by manually counting and microscopic observation. Kruskal-Wallis test was used to compare platelet parameters between MYH9-RD and control groups. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of platelet parameters for MYH9-RD. Results:In MYH9-RD patients the median value of mean platelet volume (MPV) was 13.4 (11.2, 14.7) fl, immature platelet fraction (IPF) was 52.7% (43.5%, 58.0%), platelet large cell ratio(PLCR) was 57.6 %(45.0%, 62.9%), and microscopic large platelet ratio (PLCR-M) was 30.0% (25.0%, 30.0%).And those values weresignificantly higher than in ITP, ALL, and healthy controls (all P<0.05). Patients with MYH9 gene "head region" mutations had a lower platelet count [24.5 (15.0, 47.5)×10 9/L]than those with "tail region" mutations [69.0 (49.5, 86.3) ×10 9/L]( Z=-3.493, P<0.001), but a higher IPF ( t=2.024, P=0.044).Patients with "extra-hematological involvement had a lower platelet count than those with "isolated hematological manifestations" ( t=-2.015, P=0.043). The optimal cutoff value for diagnosing MYH9-RD with IPF was 26.7%, with a sensitivity of 100% and specificity of 98.7%; the area under the curve was 0.999 (95% CI 0.995-1.000), which was superior toMPV, PLCR and PLCR-M parameters. Conclusion:IPF is superior to other platelet parameters sush as MPV,showing high diagnostic efficacy in distinguishing MYH9-RD from ITP and ALL. It can be used as a simple and effective indicator for early screening of MYH9-RD.

Objective To explore the latent profile of health-promoting lifestyle in patients with lumbar disc herniation treated conservatively and analyze its influencing factors,so as to provide reference for the develop-ment of targeted interventions.Methods Patients with conservative treatment of Lumbar Disc Herniation at the orthopedic outpatient clinic of a tertiary hospital in Guangzhou from March to December 2024 were selected as study subjects.General Information Questionnaire,Health-Promoting Lifestyle Profile Revised-Ⅱ,Visual Analogue Scale,Oswestry Disability Index and Social Support Rating Scale were used for the investigation.Latent profile analysis was used to explore the potential categories of health-promoting lifestyle in patients with lumbar disc her-niation and the influencing factors were identified by univariate analysis and disordered multiple logistic regression analysis.Results A total of 422 lumbar disc herniation patients treated conservatively were included and the score of Health-Promoting Lifestyle Profile Revised-Ⅱ Scale was(102.44±13.19)points.The health-promoting lifestyle of patients with lumbar disc herniation can be divided into three potential profile:low health promotion group-low responsibility and less exercise type(18.7%),balanced health promotion group(51.7%)and high health promotion group-spiritual social leading type(29.6%).The results of logistic regression analysis showed that course of disease,oswestry disability index,social support level and take regular physical exercise are the influenc-ing factors of health-promoting lifestyle in patients with conservative treatment of lumbar disc herniation(P<0.05).Conclusions There is heterogeneity in the health-promoting lifestyle in patients with conservative treat-ment of lumbar disc herniation.Nursing staff can carry out targeted interventions according to the latent profile type of health-promoting lifestyle in lumbar disc herniation patients treated conservatively to improve their health-promoting lifestyle.

Objective:To explore the screening value of platelet parameters from blood cell analysis for MYH9-related disorders(MYH9-RD).Methods:A cross-sectional study was conducted with 38 patients diagnosed with MYH9-RD at Shenzhen Children's Hospital from May 1, 2016, to August 31, 2024, including 24 males and 14 females; the median age was 11.5 (3.8, 35) years; categorized by gene mutation location into "head region" ( n=8 ) and "tail region" ( n=30); and by clinical manifestations into " isolated hematological manifestations" ( n=16) and "hematological manifestations with extra-hematological involvement"( n=22). The control groups included 39 cases of immune thrombocytopenia (ITP), 38 cases of acute lymphoblastic leukemia (ALL), and 40 healthy individuals. Platelet-related parameters were detected by hematology analyzer, and platelet counts and sizes were confirmed by manually counting and microscopic observation. Kruskal-Wallis test was used to compare platelet parameters between MYH9-RD and control groups. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of platelet parameters for MYH9-RD. Results:In MYH9-RD patients the median value of mean platelet volume (MPV) was 13.4 (11.2, 14.7) fl, immature platelet fraction (IPF) was 52.7% (43.5%, 58.0%), platelet large cell ratio(PLCR) was 57.6 %(45.0%, 62.9%), and microscopic large platelet ratio (PLCR-M) was 30.0% (25.0%, 30.0%).And those values weresignificantly higher than in ITP, ALL, and healthy controls (all P<0.05). Patients with MYH9 gene "head region" mutations had a lower platelet count [24.5 (15.0, 47.5)×10 9/L]than those with "tail region" mutations [69.0 (49.5, 86.3) ×10 9/L]( Z=-3.493, P<0.001), but a higher IPF ( t=2.024, P=0.044).Patients with "extra-hematological involvement had a lower platelet count than those with "isolated hematological manifestations" ( t=-2.015, P=0.043). The optimal cutoff value for diagnosing MYH9-RD with IPF was 26.7%, with a sensitivity of 100% and specificity of 98.7%; the area under the curve was 0.999 (95% CI 0.995-1.000), which was superior toMPV, PLCR and PLCR-M parameters. Conclusion:IPF is superior to other platelet parameters sush as MPV,showing high diagnostic efficacy in distinguishing MYH9-RD from ITP and ALL. It can be used as a simple and effective indicator for early screening of MYH9-RD.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

Objective To explore the latent profile of health-promoting lifestyle in patients with lumbar disc herniation treated conservatively and analyze its influencing factors,so as to provide reference for the develop-ment of targeted interventions.Methods Patients with conservative treatment of Lumbar Disc Herniation at the orthopedic outpatient clinic of a tertiary hospital in Guangzhou from March to December 2024 were selected as study subjects.General Information Questionnaire,Health-Promoting Lifestyle Profile Revised-Ⅱ,Visual Analogue Scale,Oswestry Disability Index and Social Support Rating Scale were used for the investigation.Latent profile analysis was used to explore the potential categories of health-promoting lifestyle in patients with lumbar disc her-niation and the influencing factors were identified by univariate analysis and disordered multiple logistic regression analysis.Results A total of 422 lumbar disc herniation patients treated conservatively were included and the score of Health-Promoting Lifestyle Profile Revised-Ⅱ Scale was(102.44±13.19)points.The health-promoting lifestyle of patients with lumbar disc herniation can be divided into three potential profile:low health promotion group-low responsibility and less exercise type(18.7%),balanced health promotion group(51.7%)and high health promotion group-spiritual social leading type(29.6%).The results of logistic regression analysis showed that course of disease,oswestry disability index,social support level and take regular physical exercise are the influenc-ing factors of health-promoting lifestyle in patients with conservative treatment of lumbar disc herniation(P<0.05).Conclusions There is heterogeneity in the health-promoting lifestyle in patients with conservative treat-ment of lumbar disc herniation.Nursing staff can carry out targeted interventions according to the latent profile type of health-promoting lifestyle in lumbar disc herniation patients treated conservatively to improve their health-promoting lifestyle.