Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To observe the effect of Zha's manipulation combined with muscle energy technique(MET)on neck and shoulder pain and Neck Disability Index(NDI)of patients with second and third cervical facet joint disorders,and then to find out a precise,safe and effective therapies for the its treatment.Methods A randomized controlled trial was conducted for 60 patients with second and third cervical facet joint disorders who met the inclusion criteria.The patients who admitted to the outpatient clinic of the Rehabilitation Department of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine from June 2023 to July 2024 were randomly divided into a treatment group and a control group,with 30 patients in each group.The treatment group was given the treatment of Zha's manipulation combined with MET,and the control group was given conventional tuina therapy.The treatment was performed once a day and the course of treatment covered five consecutive treatments.The changes of Visual Analogue Scale(VAS)scores of pain and NDI scores in the two groups before and after treatment were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)During the treatment,there were no fell-off cases in the two groups,and all patients completed the whole course of treatment.(2)After five days of treatment,the total effective rate of the treatment group was 96.7％(29/30),and that of the control group was 86.7％(26/30);the intergroup comparison(tested by rank sum test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS scores of neck pain in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the VAS scores of neck pain in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the NDI scores for evaluating the cervical vertebra function in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement of NDI scores in the treatment group on was significantly superior to that in the control group(P＜0.05).Conclusion Zha's manipulation combined with MET therapy can effectively alleviate pain and improve the cervical vertebra function of patients with second and third cervical facet joint disorders,and its therapeutic efficacy is superior to that of conventional tuina therapy.

Objective To investigate the effects of emergency endovascular treatment on the short-term and long-term prognosis of patients with minor stroke(National Institutes of Health stroke scale[NIHSS]score≤5)caused by posterior circulation large vessel occlusion(LVO).Methods A retrospective analysis was performed on consecutive patients with minor stroke caused by posterior circulation LVO admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University from July 2019 to March 2024.The patients were divided into the emergency endovascular treatment group and the standard medical treatment group according to the treatment method.Baseline and clinical data were collected from all patients enrolled,including age,sex,smoking history,history of alcohol consumption,medical history(hypertension,diabetes,hyperlipidemia,atrial fibrillation,transient ischemic attack[TIA],blood pressure on admission,stroke history,coronary heart disease),intravenous thrombolysis,tandem lesions,posterior circulation Alberta stroke program early CT score(pc-ASPECTS)on admission,NIHSS score on admission and discharge,time from onset to admission,responsible occluded vessel(basilar artery,left vertebral artery,right vertebral artery),vertebral artery development(left vertebral artery dominant,right vertebral artery dominant,bilateral vertebral artery dominant),non-lesion side vertebral artery development(poor,good,not applicable),basilar artery on CT angiography(BATMAN)score,leptomeningeal branch compensation(open,not open),surgery-related indicators(number of thrombectomy passes[≤2 times,＞2 times],rescue interventions[stent placement,balloon dilation,arterial thrombolysis,intra-arterial tirofiban infusion],immediate postoperative modified thrombolysis in cerebral infarction[mTICI]grade≥2b[successful recanalization],anesthesia method[general,local],endotracheal intubation status[yes,no],duration of mechanical ventilation[not using a ventilator or successfully intubation for≤24 hours and＞24 hours]),in-hospital systematic complications(deep-vein thrombosis,urinary tract infection,lung infection).The primary outcome for short-term prognosis was an excellent outcome(modified Rankin scale[mRS]score of 0-1)within 90 days after onset.Secondary outcomes included a good outcome(mRS score of 0-2)within 90days after onset,recurrent ischemic stroke within 90 days after onset,all-cause mortality within 90 days after onset.Safety outcomes were symptomatic intracerebral hemorrhage(sICH)within 24 hours of treatment(NIHSS score increased by≥4 points or increased level of consciousness score by≥1 point compared with admission,with visible hemorrhagic lesions on follow-up CT scan)and early neurological deterioration(END,NIHSS score increased by≥2 points or motor score increased by≥1 point compared with admission,within 24 hours after treatment).Long-term outcome was defined as recurrent ischemic stroke within 1 year after onset.Short-term and safety outcomes were compared between the emergency endovascular treatment group and the standard medical treatment group.Kaplan-Meier survival curves was used to evaluate the effect of emergency endovascular treatment on the long-term prognosis.Based on the mRS score at 90 days from onset,all patients were divided into an excellent outcome(mRS score 0-1)group and a non-excellent outcome(mRS score 2-6)group.Baseline and clinical data were compared across the two groups.Variables with statistically significant differences were included in the multivariate Logistic regression analysis to investigate the influencing factor of 90-day excellent outcomes in patients with minor stroke caused by posterior circulation LVO.Results A total of 56 patients with minor stroke caused by posterior circulation LVO were enrolled,including 18 patients in the emergency endovascular treatment group and 38 patients in the standard medical treatment group.45 patients achieved excellent outcomes and 11 patients achieved non-excellent outcomes.(1)The emergency endovascular treatment group had lower pc-ASPECTS on admission(8.0[7.0,9.0]points vs.9.0[8.0,10.0]points,P=0.043)and There were no statistically significant differences in the excellent outcome rate,good outcome rate,and ischemic stroke recurrence rate within 90 days after onset between the two groups(all P＞0.05).No all-cause mortality occurred within 90 days after onset in either group.In the emergency endovascular treatment group,one patient developed sICH and one developed END within 24 hours after treatment.(3)No recurrent ischemic stroke in the emergency endovascular treatment group within 1 year after onset,while 3cases(7.89%)of recurrence were observed within 1year after onset in the standard medical treatment group.The Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the incidence of ischemic stroke within one year after onset between the two groups(P=0.341).(4)There were statistically significant differences between patients with excellent outcome and patients with non excellent outcome in drinking history,diabetes history,NIHSS score after discharge,distribution of responsible occlusive vessels,and distribution of vertebral artery development(all P＜0.05).The results of multivariate Logistic regression analysis showed that the NIHSS score at discharge was an independent influencing factor for excellent outcome at 90 days after onset in patients with minor stroke caused by posterior circulation LVO(OR,0.448,95%CI 0.275-0.728,P=0.001).Conclusions This study shows potential safety and effectiveness of emergency endovascular treatment on patients with minor stroke caused by posterior circulation LVO,but it is not superior to standard medical treatment in terms of short-term and long-term outcomes.Further large-sample randomized controlled trials are warranted to validate the findings of this study.

Objective To investigate the effects of emergency endovascular treatment on the short-term and long-term prognosis of patients with minor stroke(National Institutes of Health stroke scale[NIHSS]score≤5)caused by posterior circulation large vessel occlusion(LVO).Methods A retrospective analysis was performed on consecutive patients with minor stroke caused by posterior circulation LVO admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University from July 2019 to March 2024.The patients were divided into the emergency endovascular treatment group and the standard medical treatment group according to the treatment method.Baseline and clinical data were collected from all patients enrolled,including age,sex,smoking history,history of alcohol consumption,medical history(hypertension,diabetes,hyperlipidemia,atrial fibrillation,transient ischemic attack[TIA],blood pressure on admission,stroke history,coronary heart disease),intravenous thrombolysis,tandem lesions,posterior circulation Alberta stroke program early CT score(pc-ASPECTS)on admission,NIHSS score on admission and discharge,time from onset to admission,responsible occluded vessel(basilar artery,left vertebral artery,right vertebral artery),vertebral artery development(left vertebral artery dominant,right vertebral artery dominant,bilateral vertebral artery dominant),non-lesion side vertebral artery development(poor,good,not applicable),basilar artery on CT angiography(BATMAN)score,leptomeningeal branch compensation(open,not open),surgery-related indicators(number of thrombectomy passes[≤2 times,＞2 times],rescue interventions[stent placement,balloon dilation,arterial thrombolysis,intra-arterial tirofiban infusion],immediate postoperative modified thrombolysis in cerebral infarction[mTICI]grade≥2b[successful recanalization],anesthesia method[general,local],endotracheal intubation status[yes,no],duration of mechanical ventilation[not using a ventilator or successfully intubation for≤24 hours and＞24 hours]),in-hospital systematic complications(deep-vein thrombosis,urinary tract infection,lung infection).The primary outcome for short-term prognosis was an excellent outcome(modified Rankin scale[mRS]score of 0-1)within 90 days after onset.Secondary outcomes included a good outcome(mRS score of 0-2)within 90days after onset,recurrent ischemic stroke within 90 days after onset,all-cause mortality within 90 days after onset.Safety outcomes were symptomatic intracerebral hemorrhage(sICH)within 24 hours of treatment(NIHSS score increased by≥4 points or increased level of consciousness score by≥1 point compared with admission,with visible hemorrhagic lesions on follow-up CT scan)and early neurological deterioration(END,NIHSS score increased by≥2 points or motor score increased by≥1 point compared with admission,within 24 hours after treatment).Long-term outcome was defined as recurrent ischemic stroke within 1 year after onset.Short-term and safety outcomes were compared between the emergency endovascular treatment group and the standard medical treatment group.Kaplan-Meier survival curves was used to evaluate the effect of emergency endovascular treatment on the long-term prognosis.Based on the mRS score at 90 days from onset,all patients were divided into an excellent outcome(mRS score 0-1)group and a non-excellent outcome(mRS score 2-6)group.Baseline and clinical data were compared across the two groups.Variables with statistically significant differences were included in the multivariate Logistic regression analysis to investigate the influencing factor of 90-day excellent outcomes in patients with minor stroke caused by posterior circulation LVO.Results A total of 56 patients with minor stroke caused by posterior circulation LVO were enrolled,including 18 patients in the emergency endovascular treatment group and 38 patients in the standard medical treatment group.45 patients achieved excellent outcomes and 11 patients achieved non-excellent outcomes.(1)The emergency endovascular treatment group had lower pc-ASPECTS on admission(8.0[7.0,9.0]points vs.9.0[8.0,10.0]points,P=0.043)and There were no statistically significant differences in the excellent outcome rate,good outcome rate,and ischemic stroke recurrence rate within 90 days after onset between the two groups(all P＞0.05).No all-cause mortality occurred within 90 days after onset in either group.In the emergency endovascular treatment group,one patient developed sICH and one developed END within 24 hours after treatment.(3)No recurrent ischemic stroke in the emergency endovascular treatment group within 1 year after onset,while 3cases(7.89%)of recurrence were observed within 1year after onset in the standard medical treatment group.The Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the incidence of ischemic stroke within one year after onset between the two groups(P=0.341).(4)There were statistically significant differences between patients with excellent outcome and patients with non excellent outcome in drinking history,diabetes history,NIHSS score after discharge,distribution of responsible occlusive vessels,and distribution of vertebral artery development(all P＜0.05).The results of multivariate Logistic regression analysis showed that the NIHSS score at discharge was an independent influencing factor for excellent outcome at 90 days after onset in patients with minor stroke caused by posterior circulation LVO(OR,0.448,95%CI 0.275-0.728,P=0.001).Conclusions This study shows potential safety and effectiveness of emergency endovascular treatment on patients with minor stroke caused by posterior circulation LVO,but it is not superior to standard medical treatment in terms of short-term and long-term outcomes.Further large-sample randomized controlled trials are warranted to validate the findings of this study.

Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.

Objective To explore the efficacy of repetitive peripheral magnetic stimulation(rPMS)in patients with lumbar disc herniation(LDH).Methods From March 2023 to March 2024,60 LDH patients were recruited in the inpatient or outpatient department of the rehabilitation department of a tertiary hospital.All patients were randomly assigned to the rPMS group or the conventional group,30 cases in each group.Both groups received routine physical therapy,and the rPMS group was treated with rPMS on this basis.VAS,JOA,and neurophysiological tests were performed before intervention and 2 weeks after intervention.Results The VAS and JOA scores of the two groups were significantly lower than those before treatment(P<0.05).Compared with the conventional group,the VAS and JOA scores of the rPMS group were significantly lower(P<0.05).Compared before and after treat-ment,the neuroelectrophysiological examination of the rPMS group was significantly improved(P<0.05).After 2 weeks of treatment,the tibial nerve motor conduction velocity,H reflex latency and IP peak in the conventional group were significantly faster than those before treatment(P<0.05).After 2 weeks of treatment,compared with the conventional group,there were significant differences in tibial nerve motor conduction velocity,peroneal nerve motor conduction velocity,superficial peroneal nerve sensory conduction velocity,sural nerve sensory conduction velocity,H reflex latency and IP peak(P<0.05).Conclusion rPMS can significantly improve and restore pain and nerve injury in patients with LDH.rPMS can be used as an effective adjuvant therapy.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.

Optimizing the drug price management mechanism and improving the availability and affordability of drugs are important in deepening the medical and health reform. The price of drugs in the United States has always been higher than the world average. The price of drugs, the total expenditure on drugs and the personal burden of patients have shown an increasing trend. By exploring the causes of high drug prices in the United States, the author found that there were four main reasons for the current situation of drug prices in the United States, including the interests of enterprises, the limited competition mechanism of the US drug market, relatively insufficient market bargaining power of the US payers, and opaque mechanism of price formation.Firstly, pharmaceutical companies try to achieve their interests by raising drug prices. Secondly, the price formation mechanism of the United States drug market is affected by the price strategy of pharmaceutical companies, and government policies also indirectly affect the role of the market. Thirdly, the payers in the United States are relatively scattered, so that the market bargaining power is relatively insufficient.Fourthly, due to the numerous drug circulation links and stakeholders, the drug price formation mechanism is opaque and lacks supervision. Therefore, when strengthening drug price management in China, we should build a coordination mechanism between the government and the market on the basis of the existing basic economic system and drug management mechanism, establish the strategic purchase and negotiation position of medical insurance for drugs, enhance the transparency of drug circulation and trading, and establish a scientific pricing system. It is also important to promote drug innovation and ensure drug quality.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.