Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To observe any effect of dynamic instability training on the balance and posture control of persons with chronic ankle instability (CAI).Methods:Thirty persons with CAI were divided at random into a control group and an observation group, each of 15. Both groups received routine rehabilitation interventions (including ankle strength training, kinesio taping, and vibration training), while the observation group additionally underwent 20 minutes of dynamic instability training daily, 5 days a week for 4 consecutive weeks. Before and after the treatment, everyone′s balance was evaluated using the Berg balance scale (BBS) and the star moving balance test (SEBT). Surface electromyography (sEMG) was used to collect electromyograms of the affected peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles of both groups within 100ms before and after landing in the jump-landing test. The intensity of muscle activation was thus analyzed.Results:After the treatment there was significant improvement in the average BBS scores, anterior medial SEBT, medial SEBT and posterior medial SEBT results of both groups. On average, all three SEBT results [(80.27±4.06)cm, (90.27±4.06)cm and (97.73±3.47)cm respectively] were significantly better in the observation group than in the control group. The standardized integrated electromyographs of the peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles on the affected sides showed significant improvement compared with before the treatment, but there too the observation group′s results were significantly better than those of the control group.Conclusions:Combining dynamic instability training with conventional rehabilitation can further improve the balance and postural control of persons with chronic ankle instability.

Objective:To observe any effect of dynamic instability training on the balance and posture control of persons with chronic ankle instability (CAI).Methods:Thirty persons with CAI were divided at random into a control group and an observation group, each of 15. Both groups received routine rehabilitation interventions (including ankle strength training, kinesio taping, and vibration training), while the observation group additionally underwent 20 minutes of dynamic instability training daily, 5 days a week for 4 consecutive weeks. Before and after the treatment, everyone′s balance was evaluated using the Berg balance scale (BBS) and the star moving balance test (SEBT). Surface electromyography (sEMG) was used to collect electromyograms of the affected peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles of both groups within 100ms before and after landing in the jump-landing test. The intensity of muscle activation was thus analyzed.Results:After the treatment there was significant improvement in the average BBS scores, anterior medial SEBT, medial SEBT and posterior medial SEBT results of both groups. On average, all three SEBT results [(80.27±4.06)cm, (90.27±4.06)cm and (97.73±3.47)cm respectively] were significantly better in the observation group than in the control group. The standardized integrated electromyographs of the peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles on the affected sides showed significant improvement compared with before the treatment, but there too the observation group′s results were significantly better than those of the control group.Conclusions:Combining dynamic instability training with conventional rehabilitation can further improve the balance and postural control of persons with chronic ankle instability.

Objective:To explore any effect of supplementing telerehabilitation with wearable technology on the upper limb functioning and activity of stroke survivors.Methods:Fifty family-based stroke survivors were randomly divided into an experimental group and a control group, each of 25. In addition to routine medication, the control group was given routine rehabilitation guidance at home, while the experimental group was guided using telerehabilitation and wearable technology. The guidance lasted 20 minutes, 5 days a week for 8 weeks. Before and after the intervention, both groups′ upper limb motor functioning was evaluated using the Fugl-Meyer upper extremity assessment (FMA-UE). The modified Ashworth scale (MAS) was used to quantify hemiplegic muscle spasms, and ability in the activities of daily living was quantified using the modified Barthel index (MBI). A wireless motion capture system generated average trace error (ATE) and test execution time data.Results:There were no significant differences between the two groups before the experiment. After the 8 weeks, significant improvement was observed in both groups′ average FMA, MAS and MBI scores, with those of the experimental group significantly better, on average, than those of the control group. There was also a significant improvement in the average ATE and time data in both groups, with significantly better results in the treatment group.Conclusions:Telerehabilitation based on wearable technology can distinctly improve upper limb motor function and ability in the activities of daily living after a stroke.

Objective:To explore any effect of supplementing telerehabilitation with wearable technology on the upper limb functioning and activity of stroke survivors.Methods:Fifty family-based stroke survivors were randomly divided into an experimental group and a control group, each of 25. In addition to routine medication, the control group was given routine rehabilitation guidance at home, while the experimental group was guided using telerehabilitation and wearable technology. The guidance lasted 20 minutes, 5 days a week for 8 weeks. Before and after the intervention, both groups′ upper limb motor functioning was evaluated using the Fugl-Meyer upper extremity assessment (FMA-UE). The modified Ashworth scale (MAS) was used to quantify hemiplegic muscle spasms, and ability in the activities of daily living was quantified using the modified Barthel index (MBI). A wireless motion capture system generated average trace error (ATE) and test execution time data.Results:There were no significant differences between the two groups before the experiment. After the 8 weeks, significant improvement was observed in both groups′ average FMA, MAS and MBI scores, with those of the experimental group significantly better, on average, than those of the control group. There was also a significant improvement in the average ATE and time data in both groups, with significantly better results in the treatment group.Conclusions:Telerehabilitation based on wearable technology can distinctly improve upper limb motor function and ability in the activities of daily living after a stroke.

Health consumption upgrading is an important way to benefit residents'livelihood,protect health and promote the construction of healthy China.It analyzes the practical foundation and development dilemma of China's health consumption upgrading in the new period through literature and logical analysis,and puts forward strategies to alleviate the dilemma.It concludes that in the new period,China's health consumption upgrading has the practical foundation of significant effect of health poverty alleviation policies,continuous upgrading of national health consumption concepts,and continuous emergence of health science and technology innovations,but also faces the development dilemmas of unstable health market order,insufficient supply of health products,insufficient application of health science and technology,and lack of deep cultivation of health literacy.Accordingly,the following strategies are proposed to alleviate the difficulties:strengthen top-level design to create a new"environment"for health consumption;promote diversified participation to meet the new"demand"for health consumption;strengthen technology-driven to build a new"industry"for health consumption;and cultivate health literacy.Cultivating health literacy and cultivating new"potential"for healthy consumption.

Objective To investigate the effect of respiratory training based on core stability training on feedforward control in pa-tients with chronic nonspecific low back pain(CNLBP). Methods A total of 60 patients with CNLBP in Jiaxing Second Hospital from January,2022 to March,2023 were ran-domly divided into control group(n=30)and experimental group(n=30).Both groups received health educa-tion,physical factor therapy and core stability training,while the experimental group received respiratory training in addition,for four weeks.Visual Analogue Scale(VAS)score,Japanese Orthopaedic Association low back pain(JOA)score and Oswestry Dysfunction Index(ODI)were compared between two groups before and after treat-ment,while surface electromyography was used to detect the root mean square(RMS)and integrated electromy-ography(iEMG)of transversus abdominis,multifidus and triceps(movement muscles),and the activation se-quence and relative activation time of transversus abdominis,multifidus and triceps were calculated. Results After treatment,the scores of VAS,JOA and ODI improved significantly in both groups(|t|>8.515,P<0.001),and the scores were better in the experimental group than in the control group(|t|>2.089,P<0.05).RMS and iEMG of transversus abdominis and multifidus improved significantly after treatment in both groups(|t|>18.831,P<0.001),and were significantly better in the experimental group(|t|>3.481,P<0.05).The transversus abdominis and multifidus in both groups were activated before the movement muscles,and the relative activation time of transversus abdominis and multifidus increased in negative(|t|>48.115,P<0.001),the experimental group being better(|t|>3.229,P<0.05). Conclusion Combination of core stability training and respiratory training is beneficial in reducing the pain of patients with CNLBP,reducing the lumbar dysfunction,improving the order of muscle activation,and strengthening feed-forward control.

OBJECTIVE To analyze the chemical constituents from classical prescription Xiehuang San(XHS)standard decoc-tion by UPLC-Q-TOF-MS technology,and classify the chemical composition and analyze the representative components.METHODS Acquity HSS T3 column(2.1 mm×100 mm,1.8 μm)was used as the chromatographic column,with 0.1%formic acid solution-0.1%formic acid acetonitrile as the mobile phase for gradient elution.The volume flow rate was 0.4 mL·min-1 and the column tem-perature was 40℃.Mass spectrometry data of XHS were collected in positive and negative ion modes.The chemical constituents from classical prescription XHS were analyzed and identified by Masslynx 4.1 software comparison with reference materials,mass spectrome-try data analysis and reference to relevant literature.RESULTS A total of 107 compounds were analyzed and identified from XHS,including 45 flavonoids,27 triterpenoids,11 monoterpenoids,10 phenylpropanoids,6 chromogenic ketones,5 alkaloids and 3 other other compounds.CONCLUSION The study provides an experimental basis for the further research on the substance basis and qual-ity control of XHS.

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

Objective To analyze risk factors of acute respiratory failure(ARF)in patients with hypertriglyceridemia acute pancreatitis(HTG-AP)and construct a risk prediction model.Methods A total of 222 HTG-AP patients were included in this study and divided into the non-ARF group(176 cases)and the ARF group(46 cases)according to diagnostic guidelines for ARF.Clinical data of the two groups were compared and the predictive factors were screened.These selected factors were then utilized in a multivariate Logistic regression analysis to construct a Logistic regression model.Subsequent evaluation of the model′s predictive ability,accuracy and clinical utility was conducted through ROC,curve analysis,calibration plot examination and decision curve analysis(DCA),respectively.Results Compared with the non-ARF group,the levels of high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL)-C and albumin(ALB)were decreased in the ARF group(P＜0.05),while the levels of creatinine(Cr),urea nitrogen(BUN),aspartate aminotransferase(AST)and C-reactive protein(CRP)were increased,and the incidence of pleural fluid and ascites was also increased(P＜0.05).Multivariate Logistic regression analysis showed that higher levels of Cr and AST,lower levels of ALB,HDL-C and ascites were independent risk factors for HTG-AP complicated ARF(P＜0.05).Based on these results,a column-line prediction model for HTG-AP complicated ARF was established.After internal verification,the area under curve(AUC)of receiver operating characteristic(ROC)curve of the nomogram model was 0.952(95%CI:0.923-0.981),the Youden index was 0.808 and the sensitivity and specificity were 93.33%and 87.43%,respectively.The calibration curve showed that the probability of HTG-AP concurrent ARF predicted by the model was in good agreement with the actual probability.The DCA curve showed that the model had certain clinical value.Conclusion The nomogram prediction model combined could provide a scheme for the clinical prevention of HTG-AP complicated with ARF.