Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

BACKGROUND: The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs. METHODS: This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables. RESULTS: The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r  = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r  = -0.662, P <0.01). Additionally, SA ( r  = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r  = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P  = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P  = 0.041), body mass index (β = -0.061, P  = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG. CONCLUSION Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans ; Female ; Male ; Osteoarthritis, Knee/pathology* ; Middle Aged ; Retrospective Studies ; Aged ; Patellofemoral Joint/pathology* ; Magnetic Resonance Imaging ; Adult ; Patella/pathology* ; Radiography

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

OBJECTIVE To observe the clinical efficacy and safety of tofacitinib combined with hydroxychloroquine in the treatment of refractory rheumatoid arthritis （RA）. METHODS From January 1， 2021 to January 1， 2022， 120 patients with refractory RA were selected as the study objects. According to the principle of random allocation， the patients were divided into group A， group B and group C， with 40 patients in each group. Group A was given Tofacitinib citrate tablet + Hydroxychloroquine sulfate tablet； group B was given Tofacitinib citrate tablet + Methotrexate tablet； group C was given Tofacitinib citrate tablet + Leflunomide tablet. Three groups were given relevant medicine for 6 months. Therapeutic efficacy and disease activity score 28 （DAS 28） of 3 groups as well as Sharp score， the levels of biochemical indicators [erythrocyte sedimentation rate （ESR）， C- reactive protein （CRP）]， immune indexes [rheumatoid factor （RF）， anti-cyclic peptide containing citrulline （anti-CCP） antibody]， serum cytokine indicators [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] before and after treatment were observed； the occurrence of adverse drug reactions during treatment was recorded. RESULTS After treatment， the proportions of ACR50 and ACR70 patients in group A were significantly higher than groups B and C （P＜0.05）； DAS28 score， Sharp score， biochemical indicators， immune indexes and serum cytokine indicators of 3 groups were significantly lower than before treatment （P＜0.05）， and gradually decreased with prolonged treatment time； after 6 months of treatment， DAS28 score， Sharp score， RF， anti-CCP antibody， the levels of IL-6 and TNF-α in group A were significantly lower than group B and C （P＜0.05）. There was no significant difference in the incidence of diarrhea， nausea and vomiting， leukopenia， rash， abnormal liver and kidney function， or dizziness among 3 groups （P＞0.05）. CONCLUSIONS Tofacitinib combined with hydroxychloroquine shows good efficacy and safety for refractory RA.

Objective To compare the effect of routine speech training and computer-assisted training on post-stroke dysarthria. Methods From March,2021 to April,2023,72 patients with post-stroke dysarthria in Beijing Bo'ai Hospital were ran-domly divided into control group(n=36)and experimental group(n=36).Both groups received routine rehabili-tation,while the control group received routine speech training,and the experimental group received computer-assisted training,for four weeks.They were assessed with modified Frenchay Dysarthria Assessment(m-FDA)and Speech Intelligibility(SI)before and after intervention. Results Eight cases in the control group and one case in the experimental group dropped down.The scores of m-FDA and SI improved in both groups after treatment(|Z|＞4.183,P＜0.001),and there was no significant difference between two groups(|Z|＜1.598,P＞0.05).Noninferiority of m-FDA was found between two groups(|t|＞3.656,P＜0.001). Conclusion Computer-assisted training could improve the speech function of patients with post-stroke dysarthria,simi-lar to routine speech training.

New daily persistent headache(NDPH)is a kind of persistent headache that patients can i-dentify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.

Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.