ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

Objective:To observe the effect of robot-assisted upper-limb training on motor function in stroke patients with hemiplegia,utilizing ultrasound shear wave elastography(SWE)for quantitative assessment of muscle fiber pa-rameters,and to explore the application value of SWE in evaluating stroke rehabilitation outcomes.Method:Sixty-one stroke patients with upper-limb dysfunction admitted to the Department of Rehabilitation Medicine,People's Hospital of Xinjiang Uygur Autonomous Region between August 2024 and February 2025 were randomly assigned to a control group(n=31)or an experimental group(n=30)using a random number table.The control group received conventional rehabilitation training(60 minutes/session,once daily,7 ses-sions/week for 3 weeks).The experimental group received conventional training(40 minutes)plus upper limb robot-assisted training(20 minutes),with the same frequency and duration.Both groups were assessed before and after treatment using the Brunnstrom recovery stage(BRS)for motor staging,Fugl-Meyer Assessment for Upper Extremity(FMA-UE),modified Ashworth scale(MAS),and modified Barthel index(MBI).SWE was used to measure quantitative muscle fiber parameters.Result:After treatment,both groups showed statistically significant improvements in FMA-UE and MBI scores compared to baseline(P<0.05),with significantly greater improvement in the experimental group(P<0.05).BRS scores improved significantly within the experimental group(P<0.05)but showed no significant be-tween-group difference(P>0.05).MAS scores showed no significant within-or between-group differences(P>0.05).The shear modulus(G-value)of the middle deltoid,biceps brachii,and brachioradialis(in both relaxed and stretched states)improved significantly in the experimental group compared with the control group(P<0.05).The experimental group also showed a significant increase in the triceps brachii G-value in the relaxed state compared with both baseline and the control group(P<0.05).Significant within-group improvements(P<0.05)were seen in the anterior deltoid(experimental group)and posterior deltoid(control group)in the re-laxed state,but no significant between-group differences existed(P>0.05).No significant within-or between-group differences were found in the G-value of the anterior deltoid(experimental),posterior deltoid(con-trol),or triceps brachii in the stretched state(P>0.05).Conclusion:Upper-limb rehabilitation robot-assisted training is superior to conventional rehabilitation training in improving upper-limb motor function and reducing flexor spasticity in stroke patients.SWE technology can be used in quantitatively assessing muscle structural parameters in stroke patients.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

There exist risks of ionizing radiation in radiodiagnosis examinations. Implementing shielding protection following the optimization and as low as reasonably achievable (ALARA) principles represents a measure to reduce radiation doses to patients. The implementation of shielding protection in clinical practices should meet high requirements due to variations in the modalities and items in radiodiagnosis examinations, the characteristics and irradiation method of X-ray beams, the method of automatic selection of image quality and radiation dose-related parameters by imaging equipment, the radiation sensitivity of human tissues and organs. This review introduced the shielding products, methods and effects in various radiodiagnosis examinations, as well as the current status and challenges in their applications, aiming to provide a reference for future related research and clinical practices.

Objective To investigate the drug-drug interaction between donepezil hydrochloride and moxifloxacin hydrochloride during combined administration through in vitro liver microsomal metabolism and changes in pharmacokinetic characteristics in rats.Methods A rat liver microsomal incubation system was constructed and optimized.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis of donepezil hydrochloride and high-performance liquid chromatography(HPLC)analysis of moxifloxacin hydro-chloride were performed.The pharmacokinetic and metabolic characteristics of the two drugs,alone and in combination,were compared in vitro using rat liver microsomes and in vivo using rats.Results In the liver microsomal system,the half-life(T1/2)of donepezil hydro-chloride in the combined administration 1 group was prolonged by 29.892％(P＜0.01)and the intrinsic clearance(CLint)was reduced by 23.194％(P＜0.01)compared with the donepezil hydrochloride group.Conversely,the metabolic parameters of moxifloxacin hydrochlo-ride in the combined administration 2 group did not differ significantly from that of the moxifloxacin hydrochloride group(P＞0.05).In the in vivo study,the AUC0～t and AUC0～∞ of donepezil hydrochloride in the combined administration 1 group increased by 44.259％and 44.496％,respectively,maximum plasma concentration(Cmax)increased by 117.723％,T1/2 was prolonged by 98.063％,and CLint was reduced by 35.293％,compared with that in the donepezil hydrochloride group.Moreover,the differences were all statistically significant(P＜0.05).The in vivo study findings were consistent with the results of the in vitro study.Conclusion A drug-drug interaction occurs when moxifloxacin hydrochloride is used in combination with donepezil hydrochloride.Moxifloxacin hydrochloride promotes the absorption of donepezil hydrochloride,inhibits its metabolism,slows its CLint,and increases donepezil exposure in the body.

Objective To investigate the effect of Lianpu Yin on duodenal microinflammation in rats with functional dyspepsia(FD)by regulating NLRP3 activation.Methods Wistar rats were randomly divided into blank group and model group.FD rats were reconstructed by iodoacetamide method(2%sucrose solution containing 0.1%iodoacetamide),and the model was verified.FD model rats were randomly divided into model group,Lianpu Yin group and Moxapride group by random number expression method.After a period of two weeks of administration,measurements were taken to determine the body mass,three-hour food consumption,as well as the rates of gastric emptying and intestinal propulsion.The pathological structure of duodenal tissue was observed by HE staining.The serum levels of IL-1β and IL-18 were quantified using the enzyme-linked immunosorbent assay(ELISA)method.The expression levels of NLRP3 and Caspase-1 in each group were detected by Western blot.Expression levels of NLRP3 and Caspase-1 proteins were detected by immunofluorescence.Results Compared with the blank group,body weight,food intake at 3 h,gastric emptyand intestinal propulsion rate in model group were significantly decreased(P<0.01),and inflammatory infiltration of duodenum tissue appeared in the model group.Meanwhile,the expressions of NLRP3 and Caspase-1 proteins,as well as the levels of IL-1β and IL-18 in the duodenal tissue of the model group,showed significant increasing(P<0.05).Compared with the model group,rats in the Lianpu Yin and Moxapride groups displayed significant increasing in body weight,gastric emptying rate,and intestinal propulsion rate(P<0.01).Additionally,inflammatory infiltration of duodenum tissue reduced in these groups.Furthermore,NLRP3 and Caspase-1 protein expressions,as well as IL-1β and IL-18 levels,significantly decreased in the Lianpu Yin and Moxapride groups compared to the model group(P<0.05).Conclusion Lianpu Yin can treat FD rats by inhibiting duodenal microinflammation and then restoring gastrointestinal motility,which may be related to the abnormal activation of NLRP3 inflammasome.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Objective:To observe the effect of robot-assisted upper-limb training on motor function in stroke patients with hemiplegia,utilizing ultrasound shear wave elastography(SWE)for quantitative assessment of muscle fiber pa-rameters,and to explore the application value of SWE in evaluating stroke rehabilitation outcomes.Method:Sixty-one stroke patients with upper-limb dysfunction admitted to the Department of Rehabilitation Medicine,People's Hospital of Xinjiang Uygur Autonomous Region between August 2024 and February 2025 were randomly assigned to a control group(n=31)or an experimental group(n=30)using a random number table.The control group received conventional rehabilitation training(60 minutes/session,once daily,7 ses-sions/week for 3 weeks).The experimental group received conventional training(40 minutes)plus upper limb robot-assisted training(20 minutes),with the same frequency and duration.Both groups were assessed before and after treatment using the Brunnstrom recovery stage(BRS)for motor staging,Fugl-Meyer Assessment for Upper Extremity(FMA-UE),modified Ashworth scale(MAS),and modified Barthel index(MBI).SWE was used to measure quantitative muscle fiber parameters.Result:After treatment,both groups showed statistically significant improvements in FMA-UE and MBI scores compared to baseline(P<0.05),with significantly greater improvement in the experimental group(P<0.05).BRS scores improved significantly within the experimental group(P<0.05)but showed no significant be-tween-group difference(P>0.05).MAS scores showed no significant within-or between-group differences(P>0.05).The shear modulus(G-value)of the middle deltoid,biceps brachii,and brachioradialis(in both relaxed and stretched states)improved significantly in the experimental group compared with the control group(P<0.05).The experimental group also showed a significant increase in the triceps brachii G-value in the relaxed state compared with both baseline and the control group(P<0.05).Significant within-group improvements(P<0.05)were seen in the anterior deltoid(experimental group)and posterior deltoid(control group)in the re-laxed state,but no significant between-group differences existed(P>0.05).No significant within-or between-group differences were found in the G-value of the anterior deltoid(experimental),posterior deltoid(con-trol),or triceps brachii in the stretched state(P>0.05).Conclusion:Upper-limb rehabilitation robot-assisted training is superior to conventional rehabilitation training in improving upper-limb motor function and reducing flexor spasticity in stroke patients.SWE technology can be used in quantitatively assessing muscle structural parameters in stroke patients.