BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

ObjectiveTo observe the therapeutic effects of Qishao Huoxue prescription on patients with lumbar disc herniation due to Qi stagnation and blood stasis and the effects of this prescription on hemorheological parameters and serum levels of inflammatory mediators. MethodA total of 86 patients with lumbar disc herniation due to Qi stagnation and blood stasis treated in the Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2023 to February 2024 were selected and assigned according to the random number table into observation and control groups （n=43）. Patients in both groups received lumbar traction treatment. In addition， the observation group was orally treated with Qishao Huoxue prescription and the control group with celebrex for 3 weeks. The visual analogue scale （VAS） score， Oswestry disabilitiy index （ODI） score， 12-item Short-Form Survey （SF-12） score， traditional Chinese medicine （TCM） symptom score， hemorheological parameters ［whole blood high shear viscosity， middle shear viscosity， low shear viscosity， plasma viscosity （PV）， and fibrinogen （FIB）］， and the serum levels of inflammatory mediators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and transforming growth factor-β₁ （TGF-β₁）］ were determined before and after treatment. In addition， the clinical efficacy and adverse reactions were observed and compared between the two groups. ResultAfter treatment， both groups showed declined VAS， ODI， and TCM symptom scores （P<0.05）， increased SF-12 physical component summary （PCS） and mental component summary （MCS） scores （P<0.05）. After treatment， the whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， and FIB decreased in the observation group （P<0.05）， while they did not show significant variations in the control group. After treatment， both groups of patients showed reductions in TNF-α， IL-6， and IL-1β levels and an elevation in the TGF-β₁ level （P<0.05）. Compared with the control group after treatment， the observation group showed decreases in VAS， ODI， TCM symptom scores and main symptom scores （P<0.05）， no significant differences in the secondary symptom scores， increased PCS and MCS scores （P<0.05）. The observation group outperformed the control group in terms of recovering whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， FIB， TNF-α， IL-6， IL-1β， and TGF-β₁ （P<0.05）. The total response rate in the observation group was 97.5% （40/41）， which was higher than that （88.1%， 37/42） in the control group （P<0.05）. No serious adverse reaction was observed in the two groups during the observation period. One case in the observation group showed subcutaneous bruising on the lower limbs， which gradually disappeared after withdrawal. ConclusionQishao Huoxue prescription demonstrated definite effect in treating lumbar disc herniation due to qi stagnation and blood stasis by recovering hemorheological parameters and inhibiting the expression of inflammatory mediators in the serum without inducing adverse reactions. It is worth applying in clinical practice.

ObjectiveTo evaluate the clinical effectiveness and safety of acupuncture with manipulation for lumbar disc herniation in remission period. MethodsOne hundred and four patients with lumbar disc herniation in remission were randomly divided into a treatment group and a control group， with 52 cases in each group. Treatment group applied acupuncture with manipulation of pointing， pulling， and shaking. Acupoints were selected as lumbar Jiaji （EX-B2， bilateral）， Ashi point， Shenshu （BL 23， bilateral）， Huantiao （GB 30， bilateral）， Weizhong （BL 40， opposite side of the affected area）， Chengshan （BL 57， opposite side of the affected area）. The control group applied lumbar traction plus acupoint ultrasonic pulse penetration therapy （acupoints selection same as the treatment group）； 20 minutes each time， 3 times a week， a total of 3 weeks for both groups. The primary outcome was the improvement rate of lumbar disc herniation symptoms and signs， which was calculated at 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up， respectively； the secondary outcome were the Japanese Orthopaedic Association （JOA） scores， Visual Analogue Scale （VAS） scores， and Oswestry Disability Index （ODI） scores （including ODI total scores， sitting scores and standing scores）， which were evaluated before treatment， 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up； clinical effectiveness was assessed at 3 months follow-up； and the occurrence of adverse events in the participants， as well as blood routine， urine routine， stool routine， and electrocardiograms before and after the treatment were recorded to evaluate safety. ResultsTwo patients from each group fell out， and 50 patients of each group were included in the outcome analysis ultimately. The scores of lumbar disc herniation symptoms and signs improved more in the treatment group than in the control group at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up （P＜0.01）. The JOA scores of participants in both groups at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up were higher than those before treatment in the same group， and the VAS scores， ODI total scores， ODI sitting scores and standing scores were significantly lower than those before treatment in the same group （P＜0.05）， and the JOA scores of patients in the treatment group were higher than those of the control group at all time points， and the VAS scores， ODI total scores， ODI sitting scores and standing score were lower than those of the control group （P＜0.05）. At the 3 months follow-up， the excellent rate of the treatment group was 70.00% （35/50） better than that of the control group， which was 50.00% （25/50） （P＜0.05）. There were no abnormalities in blood， urine， stool routines and electrocardiograms before and after treatment in both groups， and no adverse events occurred. ConclusionAcupuncture with manipulation of pointing， pulling， and shaking for treating patients with lumbar disc herniation in remission has a better safety on pain relief and improving quality of life， and the effectiveness is better than lumbar traction plus acupoint ultrasonic pulse penetration therapy.

Objective:To explore the application effect of the goal-oriented and task checklist-driven method based on higher-order thinking in operating room nursing teaching.Methods:We assigned 240 nursing students who interned in the operating room of China-Japan Union Hospital of Jilin University from March 2019 to January 2023 were into control group and observation group according to the order of admission. The control group received traditional teaching, while the observation group received goal-oriented and task checklist-driven teaching based on higher-order thinking. At the end of the internship, the two groups were compared in terms of theory and skill assessment scores, comprehensive teaching feedback, and nursing quality assessment scores. SPSS 22.0 was used to perform the t-test and χ2 test. Results:In the observation group, the scores of basic theory assessment, surgical nursing assessment, basic nursing skill assessment, and operating room nursing skill assessment were (92.69±7.90) points, (93.42±7.62) points, (92.05±7.41) points, and (94.14±7.53) points, respectively, while in the control group, the scores were (85.63±7.71) points, (84.41±6.16) points, (83.86±7.53) points, and (85.05±8.13) points, respectively, showing significant differences between the two groups ( P<0.001). The observation group had significantly higher percentages of positive teaching feedback than the control group ( P<0.05). The total score and the scores of individual domains of nursing quality were significantly higher in the observation group than in the control group ( P<0.001). Conclusions:The application of the goal-oriented and task checklist-driven learning model based on higher-order thinking in operating room nursing teaching can effectively enhance the core professional competencies and higher-order clinical thinking ability of student nurse interns, thereby improving nursing quality.

Objective: To investigate the factors affecting cataract among the elderly, so as to provide insights into cataract control. Methods: Based on the major public health monitoring project of Zhejiang Province, residents at ages of 60 years and older were selected from 7 districts (counties) using a multi-stage stratified cluster random sampling method, and were followed up every other year from 2014 to 2020. Demographics, lifestyle, dietary habits and cataract incidence were collected, and factors affecting the incidence of cataract were identified using a multivariable Cox proportional hazard regression model. Results: Totally 9 642 residents were investigated, with a mean age of (68.89±7.39) years, and including 4 635 males (48.07%). There were 828 incident cataract cases, with an incidence rate of 20.946/1 000 person-years. Multivariable Cox proportional hazard regression analysis showed that women (HR=1.695, 95%CI: 1.377-2.088), age of 65 years and older (HR=1.707-5.044, 95%CI: 1.400-7.327), overweight/obesity (HR=1.313, 95%CI: 1.131-1.524), educational level (primary school, HR=1.642, 95%CI: 1.400, 1.926; junior high school, HR=1.553, 95%CI: 1.148-2.102), annual family income (10 000 to 50 000 Yuan, HR=1.353, 95%CI: 1.155-1.585; 50 000 to 100 000 Yuan, HR=0.663, 95%CI: 0.500-0.881; 100 000 to 150 000 Yuan, HR=0.340, 95%CI: 0.204-0.565), smoking (HR=0.649, 95%CI: 0.494-0.853), frequency of vegetable intake of >3 days/week (HR=0.693, 95%CI: 0.527-0.912), frequency of fruit intake of >3 days/ week (HR=0.833, 95%CI: 0.694-0.899), frequency of egg intake of >3 days/week (HR=0.579, 95%CI: 0.450-0.745), frequency of soy products intake of >3 days/week (HR=0.706, 95%CI: 0.588-0.849), frequency of dairy products intake of >3 days/week (HR=1.510, 95%CI: 1.199-1.901) and frequency of nut intake of >3 days/week (HR=1.733, 95%CI: 1.162-2.586) were statistically associated with the development of cataract among the elderly. Conclusion Gender, age, body mass index, educational level, income, smoking, and frequency of vegetables, fruits, eggs, soy products, dairy products and nuts intake are associated with the development of cataracts.

We aimed to study the articles and applied prescriptions of Moutan Cortex in Synopsis of theGolden Chamber, summarize and analyze its laws on the disease location and disease nature, and analyze its compatibility, dosage and processing laws. Based on the knowledge of Moutan Cortex by Zhongjing, we found that the kidney, bladder, uterus and intestine involved in Zhongjing's application of peony bark prescription, which belongs to the disease of "lower abdomen" in Huangdi Nei Jing. And the prescription of Moutan Cortex mainly focused on the syndromes of "depression" and "blood stasis", which are characterised by five kinds: water depression, dampness depression, stasis-heat, blood stasis and ecchymosis. and the compatibility rule of Zhongjing application of Moutan Cortex is analyzed accordingly. In addition, the study found that as the downward movement of the disease position, the amount of Moutan Cortex increased, and the processing of the problem followed the principle of "if disease is slow onset, the Moutan Cortex heart should be removed, but if disease is acute, Moutan Cortex heart should be kept". Finally, we combined modern clinical application of Moutan Cortex with modern pharmacological research, in order to expand the scope of clinical application of Moutan Cortex and "the same treatment of different diseases" to provide theoretical guidance.

OBJECTIVE: To clarify the preparation methods of four rat models of liver ischemia/reperfusion injury (IRI) and to determine a liver IRI animal model that is consistent with clinical conditions, has stable pathological and physiological injury, and is easy to operate. METHODS: A total of 160 male Sprague-Dawley (SD) rats were randomly divided into four groups using an interval grouping method: 70% IRI (group A), 100% IRI (group B), 70% IRI with 30% hepatectomy (group C), and 100% IRI with 30% hepatectomy (group D), with 40 rats in each group. Each model was further divided into sham operation group (S group) and ischemia groups of 30, 60, and 90 minutes, with 10 rats in each group. After surgery, the survival status and awakening time of the rats were observed, and the liver lobectomy weight, bleeding volume, and hemostasis time of groups C and D were recorded. Blood samples were collected by cardiac puncture after 6 hours of reperfusion for determination the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), serum creatinine (SCr), and γ-glutamyl transpeptidase (γ-GT) in the serum to assess liver and kidney function. Hematoxylin-eosin (HE) staining and immunohistochemical staining of macrophages were performed to analyze the liver tissue structure damage from a pathological perspective. RESULTS: Rats in group A exhibited earlier awakening and acceptable mental status, while rats in the other groups showed delayed awakening and poor mental status. The hemostasis time in group D was approximately 1 second longer than that in group C. The mortality of rats subjected to 60 minutes of 70% hepatic ischemia was 0. Compared to the sham operation group, rats in each experimental group showed significant increases in serum levels of AST, ALT, ALP, BUN, SCr, and γ-GT, indicating impaired liver and kidney function in the rat models of liver IRI. In groups A, B, and C, the 90-minute ischemia subgroup exhibited more pronounced elevation in AST, ALT, ALP, BUN, SCr, and γ-GT levels compared to the 30-minute ischemia subgroup [AST (U/L): group A, 834.94±56.73 vs. 258.74±18.33; group B, 547.63±217.40 vs. 277.67±57.92; group C, 930.38±75.48 vs. 640.51±194.20; ALT (U/L): group A, 346.78±25.47 vs. 156.58±13.25; group B, 408.40±138.25 vs. 196.80±58.60; group C, 596.41±193.32 vs. 173.76±72.43; ALP (U/L): group A, 431.21±34.30 vs. 315.95±15.64; group B, 525.88±62.13 vs. 215.63±17.31; group C, 487.53±112.37 vs. 272.46±92.33; BUN (U/L): group A, 18.35±5.63 vs. 14.32±2.30; group B, 30.21±4.55 vs. 17.41±8.14; group C, 20.50±3.64 vs. 15.93±3.22; SCr (U/L): group A, 27.47±8.91 vs. 22.37±5.66; group B, 43.60±15.57 vs. 36.80±7.95; group C, 63.81±20.24 vs. 42.47±7.03; γ-GT (U/L): group A, 15.64±3.57 vs. 6.82±1.48; group B, 9.28±1.91 vs. 5.62±1.21; group C, 10.98±3.18 vs. 5.67±1.10; all P < 0.05]. The 100% IRI 90-minute group and 100% IRI 90-minute group with 30% hepatectomy exhibited more pronounced increases in the above-mentioned indicators compared to the corresponding 70% IRI control group, indicating increased liver and kidney damage in rats subjected to combined blood flow occlusion and hepatectomy. HE staining showed clear liver tissue structure with intact and orderly arranged cells in the sham operation group, while the experimental groups exhibited cell structure damage, including cell rupture or collapse, cell swelling, nuclear pyknosis, deep cytoplasm staining, cell shedding, and necrosis. The interstitium showed infiltration of inflammatory cells. Immunohistochemical staining revealed a higher number of macrophages in the experimental groups compared to the sham operation group. CONCLUSIONS Four models of liver IRI in rat were successfully established. As the duration and severity of hepatic ischemia increased, liver cell ischemia worsened, leading to increased hepatocellular necrosis and exhibiting characteristic features of liver IRI. These models can effectively simulate liver IRI following liver trauma, with the group subjected to 100% ischemia and 30% hepatectomy showing the most severe liver injury. The designed models are reasonable, easy to perform, and exhibit good reproducibility. They can be used for investigating the mechanisms, therapeutic efficacy, and diagnostic methods related to clinical liver IRI.
Rats ; Male ; Animals ; Reproducibility of Results ; Rats, Sprague-Dawley ; Liver ; Reperfusion Injury/drug therapy* ; Ischemia ; Disease Models, Animal ; Necrosis

Objective To analyze the influencing factors of unstable ventilation pressure during nasal continuous positive airway pressure(NCPAP)treatment in neonates with hyaline membrane dis-ease(HMD)and construct a nomogram model.Methods A retrospective analysis was conducted in 157 HMD neonates who underwent NCPAP treatment.The patients were divided into unstable group(n=49)and stable group(n=108)based on the occurrence of unstable ventilation pressure during treatment.Logistic regression analysis was used to identify influencing factors of unstable ventilation pressure during NCPAP treatment in HMD neonates.A nomogram model was constructed using R software,and its predictive performance was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and the Hosmer-Lemeshow goodness-of-fit test.Results Unstable venti-lation pressure occurred in 49 HMD neonates during NCPAP treatment,with an incidence rate of 31.21％(49/157).Univariate analysis showed that unstable ventilation pressure during NCPAP treatment had no relation to gestational age,gender,birth weight,delivery mode,neonatal Apgar score,catheter distortion,or excessive condensation in the tube(P＞0.05).However,NCPAP treatment duration,nasal mucosa damage,secretion blockage in the airway,and restlessness were identified as influencing factors for unstable ventilation pressure during NCPAP treatment in HMD neonates(P＜0.05).Multivariate Logistic regression analysis revealed that NCPAP treatment duration ≥72 h,nasal mucosa damage,secretion blockage in the airway,and restlessness were independent risk fac-tors for unstable ventilation pressure during NCPAP treatment in HMD neonates(P＜0.05).A no-mogram model was constructed based on these four independent risk factors.The ROC curve demon-strated good discrimination for the nomogram model,with an area under the curve of 0.801(95％CI,0.730 to 0.861).The Hosmer-Lemeshow goodness-of-fit test showed a chi-square value of 3.550 with a P-value of 0.470,and the calibration curve had a slope close to 1,indicating good fit validity for the nomogram prediction model.Conclusion The nomogram model constructed based on NC-PAP treatment duration,nasal mucosa damage,secretion blockage in the airway,and restlessness has good predictive value for the occurrence of unstable ventilation pressure during NCPAP treatment in HMD neonates.

Objective To analyze the influencing factors of unstable ventilation pressure during nasal continuous positive airway pressure(NCPAP)treatment in neonates with hyaline membrane dis-ease(HMD)and construct a nomogram model.Methods A retrospective analysis was conducted in 157 HMD neonates who underwent NCPAP treatment.The patients were divided into unstable group(n=49)and stable group(n=108)based on the occurrence of unstable ventilation pressure during treatment.Logistic regression analysis was used to identify influencing factors of unstable ventilation pressure during NCPAP treatment in HMD neonates.A nomogram model was constructed using R software,and its predictive performance was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and the Hosmer-Lemeshow goodness-of-fit test.Results Unstable venti-lation pressure occurred in 49 HMD neonates during NCPAP treatment,with an incidence rate of 31.21％(49/157).Univariate analysis showed that unstable ventilation pressure during NCPAP treatment had no relation to gestational age,gender,birth weight,delivery mode,neonatal Apgar score,catheter distortion,or excessive condensation in the tube(P＞0.05).However,NCPAP treatment duration,nasal mucosa damage,secretion blockage in the airway,and restlessness were identified as influencing factors for unstable ventilation pressure during NCPAP treatment in HMD neonates(P＜0.05).Multivariate Logistic regression analysis revealed that NCPAP treatment duration ≥72 h,nasal mucosa damage,secretion blockage in the airway,and restlessness were independent risk fac-tors for unstable ventilation pressure during NCPAP treatment in HMD neonates(P＜0.05).A no-mogram model was constructed based on these four independent risk factors.The ROC curve demon-strated good discrimination for the nomogram model,with an area under the curve of 0.801(95％CI,0.730 to 0.861).The Hosmer-Lemeshow goodness-of-fit test showed a chi-square value of 3.550 with a P-value of 0.470,and the calibration curve had a slope close to 1,indicating good fit validity for the nomogram prediction model.Conclusion The nomogram model constructed based on NC-PAP treatment duration,nasal mucosa damage,secretion blockage in the airway,and restlessness has good predictive value for the occurrence of unstable ventilation pressure during NCPAP treatment in HMD neonates.

Objective:To investigate the epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province in 2021, and provide evidence for the improvement of COVID-19 control and prevention measures.Methods:The incidence data of COVID-19 in Shangyu from December 7 to 21, 2021 was obtained from Shangyu District Center for Disease Control and Prevention. The epidemiological characteristics of the cases, i.e. the population, time and space distributions, were analyzed, and the incubation period and time-varying reproduction numbers ( R t) were calculated. Results:From December 7 to 21, 2021, a total of 380 COVID-19 cases caused by 2019-nCoV Delta variant were detected in Shangyu, the median age of the cases was 52 years, M ( Q1，Q3: 38, 61). The male to female ratio of the cases was 1∶1.25, and the cases were mainly workers (36.58%) and farmers (27.63%). The epidemic affected 9 townships (or community) of Shangyu, especially Caoe and Baiguan communities with the cases accounting for 57.10% and 31.53% respectively. The median incubation period of cases was 4.00 days, M ( Q1，Q3: 3.00, 5.75). The basic reproduction number ( R0) was 4.06, and the R t was 5.62 in early phase of the outbreak (the highest) and continuously decreased to less than 1.00 within 10 days after the detection of the outbreak. The number of COVID-19 cases decreased to 0 within 14 days after the outbreak (December 7-21), and the main detection methods were screening in centralized isolation (55.53%) and home isolation (40.00%). The infection rates of close contacts and secondary close contacts were 2.06% and 0.46% respectively. Conclusion:The epidemic of COVID-19 in Shangyu characterized by short incubation period, large number of infected people, and case clustering, suggesting the strong transmission of Delta variant (B.1.617.2). Comprehensive prevention and control measures, such as management of close contacts and secondary close contacts, and high-risk area, are essential for the rapid control of the epidemic.