ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To evaluate the clinical outcomes of posterior approach vertebral column resection (VCR) osteotomy combined with titanium mesh bone-graft fusion and internal fixation for the treatment of special type stage IIIb Kummell disease.Methods:Twelve patients (3 males, 9 females) diagnosed with special type stage IIIb Kummell disease at Zhengzhou Orthopedics Hospital between October 2015 and June 2021 were enrolled. The mean age was 59.1±5.6 years (range, 53-67 years). All patients underwent VCR osteotomy, pedicle screw fixation, and posterior bone-graft fusion using titanium mesh. Preoperative and postoperative outcomes were assessed using visual analogue scale (VAS) scores, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, American Spinal Injury Association (ASIA) grading, Cobb angle correction, and bone graft fusion rate. Intraoperative and postoperative complications were also recorded.Results:All surgeries were completed successfully. The average follow-up duration was 11.6±1.8 months (range, 10-13 months). Significant improvements were observed in VAS scores, ODI, JOA scores, and Cobb angles at both two weeks postoperatively and at the final follow-up ( P<0.05), with no significant differences between the two time points ( P>0.05). The final recovery rates were 79.5% for VAS score, 73.2% for ODI, 72.1% for JOA score, and 77.3% for Cobb angle correction. Neurological function showed marked improvement. One patient developed delayed incision healing due to fat liquefaction but recovered following physical therapy. The remaining 11 patients experienced uneventful wound healing without infection or internal fixation loosening. One patient developed postoperative deep venous thrombosis of the lower limbs, which resolved with drug therapy. Conclusion:Posterior approach VCR combined with titanium mesh bone-graft fusion and internal fixation provides an effective surgical option for stage IIIb Kummell disease characterized by fractured vertebral bodies with only the broken upper and lower endplates remaining.

Objective:To observe the improving effect of acupuncture and Tuina(Chinese therapeutic massage)combined with Ba Duan Jin(Eight-brocade Exercise)on motor function in patients with Parkinson disease(PD)in the early and middle stages.Methods:Seventy patients with early-or middle-stage PD were randomly divided into a control group and an observation group,with 35 patients in each group.The control group was given conventional treatment such as oral levodopa hydrochloride tablets;the observation group was treated with acupuncture,Tuina,and Ba Duan Jin in addition to the control group's treatment.Acupuncture and Tuina were administered twice a week,and Ba Duan Jin was performed five times a week.Each course of treatment lasted 4 weeks,and a total of 3 courses were completed.The changes in the unified Parkinson disease rating scale Ⅲ(UPDRS Ⅲ)score,Berg balance scale(BBS)score,15-meter walking speed,and 6-minute walk distance were compared between the two groups.Results:The total effective rate in the observation group was 93.6%,which was significantly higher than 45.7%in the control group(P<0.01).After 4,8,and 12 weeks of treatment,the UPDRS Ⅲ score in the observation group was significantly lower than the previous score(P<0.05);the BBS score was significantly higher than the previous score(P<0.05),and the 6-minute walk distance also significantly increased compared to the previous result(P<0.05).After 8 and 12 weeks of treatment,the 15-meter walking speed in the observation group was significantly higher than that before treatment and the previous measurement(P<0.05).In comparison with the control group,the observation group showed significantly lower UPDRS Ⅲ scores after 8 and 12 weeks of treatment(P<0.05).Additionally,after 4,8,and 12 weeks of treatment,the observation group had significantly higher BBS scores,15-meter walking speed,and the 6-minute walk distance than the control group(P<0.05).There were no significant differences in the above indicators before and after treatment in the control group(P>0.05).Conclusion:The addition of acupuncture,Tuina,and Ba Duan Jin to Western medication treatment can effectively improve motor function,balance ability,and walking ability in patients with early-or middle-stage PD.

Objective To investigate the relationships of tumor necrosis factor-α(TNF-α)and glycated hemoglobin(HbA1c)with the occurrence of painful diabetic neuropathy(PDN)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 225 patients with T2DM were enrolled and divided into PDN group(52 patients)and non-PDN group(173 patients)based on the presence of PDN.Clinical data of the two groups were collected and compared.A multivariate Logistic regres-sion model was used to analyze risk factors for PDN,and a receiver operating characteristic(ROC)curve was plotted to assess the predictive value of TNF-α and HbA1c for PDN in T2DM patients.Results Patients in the PDN group had a longer duration of T2DM,higher levels of fasting blood glu-cose(FBG),HbA1c,C-reactive protein(CRP),and TNF-α compared with the non-PDN group(P＜0.05).Multivariate Logistic regression analysis showed that a longer duration of T2DM,higher TNF-α levels,and higher HbA1c levels were independent risk factors for PDN in T2DM patients(P＜0.05,OR＞1).ROC curve analysis revealed that the area under the curve for the combined predic-tion of PDN in T2DM patients by TNF-α and HbA1c was 0.877(95％CI,0.826 to 0.916),which was greater than that of TNF-α and HbA1c alone[0.684(95％CI,0.619 to 0.745)and 0.764(95％CI,0.703 to 0.818),respectively].Conclusion High serum levels of TNF-α and HbA1c are independent risk factors for PDN in T2DM patients,and the combined detection of two biomarkers has high predictive efficacy for the risk of PDN in T2DM patients.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective To observe the value of dynamic attention aggregation network(DAANet)for automatic segmentation of anomalous origin of the left coronary artery from the pulmonary artery(ALCAPA)in CT angiography(CTA).Methods CTA data in 30 patients with ALCAPA syndrome were retrospectively enrolled.ALCAPA were segmented in CTA with DAANet based on residual edge feature(REF),pyramid dynamic attention(PDA)and dynamic global feature aggregation(DGFA)modules.Taken physician manual segmentation results as references,the results were compared with those of other networks.Results Compared with other networks,DAANet had better value for automatic segmentation of ALCAPA in CTA,which could show the details of irregular margins of left coronary artery with good continuity and high clarity,and the performance parameters were overall better.Conclusion DAANet had better performance for automatic segmentation of ALCAPA in CTA.

Objective:To evaluate the clinical outcomes of posterior approach vertebral column resection (VCR) osteotomy combined with titanium mesh bone-graft fusion and internal fixation for the treatment of special type stage IIIb Kummell disease.Methods:Twelve patients (3 males, 9 females) diagnosed with special type stage IIIb Kummell disease at Zhengzhou Orthopedics Hospital between October 2015 and June 2021 were enrolled. The mean age was 59.1±5.6 years (range, 53-67 years). All patients underwent VCR osteotomy, pedicle screw fixation, and posterior bone-graft fusion using titanium mesh. Preoperative and postoperative outcomes were assessed using visual analogue scale (VAS) scores, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, American Spinal Injury Association (ASIA) grading, Cobb angle correction, and bone graft fusion rate. Intraoperative and postoperative complications were also recorded.Results:All surgeries were completed successfully. The average follow-up duration was 11.6±1.8 months (range, 10-13 months). Significant improvements were observed in VAS scores, ODI, JOA scores, and Cobb angles at both two weeks postoperatively and at the final follow-up ( P<0.05), with no significant differences between the two time points ( P>0.05). The final recovery rates were 79.5% for VAS score, 73.2% for ODI, 72.1% for JOA score, and 77.3% for Cobb angle correction. Neurological function showed marked improvement. One patient developed delayed incision healing due to fat liquefaction but recovered following physical therapy. The remaining 11 patients experienced uneventful wound healing without infection or internal fixation loosening. One patient developed postoperative deep venous thrombosis of the lower limbs, which resolved with drug therapy. Conclusion:Posterior approach VCR combined with titanium mesh bone-graft fusion and internal fixation provides an effective surgical option for stage IIIb Kummell disease characterized by fractured vertebral bodies with only the broken upper and lower endplates remaining.

Objective To observe the value of dynamic attention aggregation network(DAANet)for automatic segmentation of anomalous origin of the left coronary artery from the pulmonary artery(ALCAPA)in CT angiography(CTA).Methods CTA data in 30 patients with ALCAPA syndrome were retrospectively enrolled.ALCAPA were segmented in CTA with DAANet based on residual edge feature(REF),pyramid dynamic attention(PDA)and dynamic global feature aggregation(DGFA)modules.Taken physician manual segmentation results as references,the results were compared with those of other networks.Results Compared with other networks,DAANet had better value for automatic segmentation of ALCAPA in CTA,which could show the details of irregular margins of left coronary artery with good continuity and high clarity,and the performance parameters were overall better.Conclusion DAANet had better performance for automatic segmentation of ALCAPA in CTA.

Objective:To observe the improving effect of acupuncture and Tuina(Chinese therapeutic massage)combined with Ba Duan Jin(Eight-brocade Exercise)on motor function in patients with Parkinson disease(PD)in the early and middle stages.Methods:Seventy patients with early-or middle-stage PD were randomly divided into a control group and an observation group,with 35 patients in each group.The control group was given conventional treatment such as oral levodopa hydrochloride tablets;the observation group was treated with acupuncture,Tuina,and Ba Duan Jin in addition to the control group's treatment.Acupuncture and Tuina were administered twice a week,and Ba Duan Jin was performed five times a week.Each course of treatment lasted 4 weeks,and a total of 3 courses were completed.The changes in the unified Parkinson disease rating scale Ⅲ(UPDRS Ⅲ)score,Berg balance scale(BBS)score,15-meter walking speed,and 6-minute walk distance were compared between the two groups.Results:The total effective rate in the observation group was 93.6%,which was significantly higher than 45.7%in the control group(P<0.01).After 4,8,and 12 weeks of treatment,the UPDRS Ⅲ score in the observation group was significantly lower than the previous score(P<0.05);the BBS score was significantly higher than the previous score(P<0.05),and the 6-minute walk distance also significantly increased compared to the previous result(P<0.05).After 8 and 12 weeks of treatment,the 15-meter walking speed in the observation group was significantly higher than that before treatment and the previous measurement(P<0.05).In comparison with the control group,the observation group showed significantly lower UPDRS Ⅲ scores after 8 and 12 weeks of treatment(P<0.05).Additionally,after 4,8,and 12 weeks of treatment,the observation group had significantly higher BBS scores,15-meter walking speed,and the 6-minute walk distance than the control group(P<0.05).There were no significant differences in the above indicators before and after treatment in the control group(P>0.05).Conclusion:The addition of acupuncture,Tuina,and Ba Duan Jin to Western medication treatment can effectively improve motor function,balance ability,and walking ability in patients with early-or middle-stage PD.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.