OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

Epilepsy is a chronic neurological disease characterized by abnormal synchronous discharges of brain neurons. The mutation of GRIN1， a key gene encoding the essential GluN1 subunit of N-methyl-D-aspartate （NMDA） receptors， is closely associated with the pathogenesis and progression of epilepsy. This review summarizes research advances in GRIN1 mutation-related epilepsy， with a focus on its molecular mechanisms， clinical phenotypes， factors influencing phenotypic heterogeneity， and treatment strategies. In terms of molecular mechanisms， GRIN1 mutations affect NMDA receptor function through gain-of-function and loss-of-function mechanisms. Clinical phenotypes show significant heterogeneity， including seizure types， age of onset， and comorbid neurodevelopmental disorders. This heterogeneity may be related to the domain where the mutation is located， the mutation type， and the degree of impact on receptor function. Regarding treatment， gain-of-function mutations can be managed with NMDA receptor antagonists， while loss-of-function mutations may be treated with positive allosteric modulators. The ketogenic diet has also demonstrated potential therapeutic effects. This review aims to provide references for basic research and clinical translation in GRIN1 mutation-related epilepsy， and to promote the development of precision diagnosis and treatment.

Retinitis pigmentosa (RP) is a genetic disorder of photoreceptor cell apoptosis and retinal pigment epithelium (RPE) cell atrophy caused by gene mutation. The clinical manifestations are night blindness, peripheral visual field loss and progressive vision loss. RPE cell apoptosis plays an important role in the progression of RP, and exogenous implantation of RPE cells as an alternative therapy has shown certain efficacy in animal experiments and clinical trials. With the diversification of cell sources, the update of surgical techniques and the continuous emergence of biological materials, more possibilities and hopes are provided for cell therapy. To further promote the development of this field in the future, it is still necessary to strengthen the cooperation between medicine, bioengineering and other disciplines in the future to jointly promote the innovation and development of therapeutic methods. It is believed that RPE cell transplantation therapy will show a brighter prospect in the future

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.

Objective:To observe the efficacy of vitrectomy combined with subretinal injection of tissue plasminogen activator (t-PA) in the treatment of macular hemorrhage (SMH).Method:An observational case series study was performed.Twelve eyes of 12 SMH patients diagnosed in Tianjin Medical University Eye Hospital were included from February 2022 to November 2022, including 11 eyes of polypoid choroidal vascular disease (PCV) and 1 eye of retinal artery aneurysm.There were 5 males and 7 females, aged 56 to 78 years old, with an average age of (65.67±8.09) years.Two eyes had intraocular lenses and 10 eyes were with cataracts.Nine cases had hypertension and 2 cases had diabetes.The duration of SMH was 2 to 25 days, with an average of (14.67±8.03) days.Vitrectomy combined with subretinal injection of t-PA was performed in the 12 eyes.All affected eyes underwent best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect ophthalmoscopy, optical coherence tomography (OCT), and ultra-wide-filed imaging examinations before and 1, 3, 6 months after surgery.The central retinal thickness (CRT) was examined using an OCT instrument.The postoperative ocular conditions and the occurrence of adverse effects were observed.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2022JS-05).Written informed consent was obtained from each patient before surgery.Results:The preoperative, 1-, 3-, and 6-month postoperative average BCVA (LogMAR) of the affected eye was 1.58±0.63, 1.12±0.49, 1.07±0.44, and 0.59±0.19, respectively, showing a statistically significant overall difference ( F=14.435, P<0.001).The BCVA at 6 months after surgery was significantly better than that before surgery ( P<0.001).The preoperative, 1-, 3-, and 6-month postoperative average CRT of the affected eye was (606.25±204.67), (379.83±92.05), (313.75±60.87), and (267.75±73.07)μm, respectively, showing a statistically significant overall difference ( F=27.720, P<0.001).The CRT at 1, 3, 6 months after surgery were significantly thinner than that before surgery (all at P<0.001).One eye had suprachoroidal hemorrhage 3 months after surgery, and 6 eyes received intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs due to recurrent PCV during follow-up, with a total of 16 injections.The average number of anti-VEGF injections at 1, 3, and 6 months after surgery was (0.3±0.5), (1.3±1.4), and (2.7±2.0) times, respectively. Conclusions:In the treatment of SMH, vitrectomy combined with subretinal injection of t-PA can improve BCVA, reduce CRT, reduce retinal damage from blood clots, and promote early postoperative visual recovery.It is a safe and effective surgical procedure.

Objective:To evaluate the accuracy, completeness, and reproducibility of domestic open-source large language models (LLM) in diabetic retinopathy (DR) patient education, and to explore their potential as intelligent virtual assistants for DR patient education.Methods:A total of 41 questions and answers related to the diagnosis and treatment of DR in five categories, namely risk factors, screening and examination, symptoms and staging, diagnosis, treatment and prognosis.All questions were repeated twice as a " new dialogue" in the LLM, and all the answers were recorded.Three senior fundus physicians independently evaluated the answers on a 6-point Likert scale for accuracy and a 3-point Likert scale for completeness and repeatability, and for each answer, the evaluator was asked to make a recommendation between the LLM and the manual answers.Five questions were randomly selected to evaluate the three open source LLM, ERNIE Bot 3.5, Qwen and Kimi chat, and the LLM with the best overall performance was selected for further evaluation in the full question bank.Results:Among the three LLM, Kimi chat had the best overall performance, Kimi chat performed best, with percentages of 6 for accuracy, 3 for completeness, and 3 for repeatability among the 5 questions at 90%, 90%, and 100%, respectively.For all questions answered, the number of words in manual replies was 106 (70, 202), which was significantly lower than 505 (386, 600) in Kimi chat ( Z=-7.866, P<0.001).There was no significant correlation between the number of Kimi chat replies and the accuracy score ( rs=-0.044, P=0.492), but it was positively correlated with the integrity score ( rs=0.239, P<0.001).The interclass correlation coefficient for accuracy and completeness scores were above 0.700 among three evaluators, with the highest agreement for repeatability at 0.853, followed by completeness of the first response at 0.771.The proportion of responses ≥5 points for accuracy was 87.0%(214/246), the proportion ≥2 points for completeness was 98.0%(241/246), and the proportion higher than 70% for repeatability was 78.5%(193/246).Kimi chat excelled in answering basic questions about the disease such as disease definition, staging, frequency of screening, and common risk factors, but performed poorly on questions involving treatment choices that require a doctor's professional judgment.The proportion of evaluators choosing Kimi chat responses as superior was 69.5% (171/246), and the reasons for non-selection included lack of characteristic answers, inclusion of too much irrelevant information, and lack of responses to questions requiring a high degree of medical expertise. Conclusions:Kimi chat answers DR-related diagnostic questions in a detailed and well-organized manner, with a high degree of accuracy, completeness and reproducibility.

Objective To evaluate the efficacy and safety of eravacycline in the treatment of complicated intra-abdominal infection(cIAI)in Chinese adult patients.Methods In this multicenter,randomized,double-blind phase Ⅲ study,cIAI patients were randomly assigned to receive either eravacycline(1.0 mg/kg,q12h)or ertapenem(1 g,q24h)by intravenous infusion for 5 to 14 days.The primary and secondary efficacy endpoints included the clinical efficacy and microbiological efficacy in different populations,including modified intention-to-treat(MITT)population,clinically evaluable(CE)population,and microbiologically evaluable(ME)population,at different time points after treatment.Clinical cure rates at specific visits were summarized and compared between treatment groups in different populations.The microbial eradication rate was calculated for the patients with baseline pathogens.The incidence of adverse events(AE)and drug-related treatment emergent adverse event(TEAE)was analyzed by treatment group.Results A total of 144 patients with cIAI who received at least one dose of the study drug were included in the MITT population.The clinical cure rate was 77.8％(56/72)in eravacycline-treated patients and 90.3％(65/72)in ertapenem-treated patients at 25-31 days after the first dose(TOC visit).When the patients who received insufficient treatment(＜72 hours)were excluded,the clinical cure rate was 83.6％(56/67)in eravacycline group and 90.3％(65/72)in ertapenem.For CE and ME patients,the clinical cure rate at TOC visit was 91.1％(51/56)and 83.3％(25/30)in eravacycline group,95.3％(61/64)and 90.9％(30/33)in ertapenem group.Eravacycline treatment achieved microbiological eradication rate of 91.3％(21/23)against Escherichia coli at TOC visit in micro-MITT population while ertapenem treatment resulted in a microbiological eradication rate of 96.2％(25/26).The microbiological efficacy of eravacycline and ertapenem against Klebsiella pneumoniae was 4/5 and 3/3,respectively.The incidence of TEAE was similar in eravacycline and ertapenem groups(75.0％vs.70.8％),most of which were mild or moderate.The AEs associated with eravacycline were mainly infusion site phlebitis(9.7％,7/72)and infusion site pain(8.3％,6/72).Conclusions Similar to ertapenem,eravacycline has good clinical and microbiological efficacy in treating cIAI.It is also safe and well-tolerated in the patients.

Objective To explore the application value of telmisartan combined with calcium dobesilate in patients with non-dipper hypertension complicated with type 2 diabetes mellitus(T2DM).Methods A total of 260 patients with non-dipper hypertension complicated with T2DM in the endocrinology department of our hospital were selected in this study from January 2021 to December 2022.All the patients were randomly divided into telmisartan group(Tel,n=110)and telmisartan+calcium dobesilate group(Tel+Cal-dob,n=150).The blood pressure level,blood pressure rhythm changes,brachial flow mediated dilatation(FMD),carotid radial pulse wave velocity(crPWV),vasomotor factors[nitric oxide(NO),endothelin-1(ET-1),vascular endothelial growth factor(VEGF)]and the incidence of adverse reactions were compared between the two groups.Results There was no significant difference in general data and biochemical indexes between the two groups(P>0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while the dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower than before treatment in both groups(P<0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower in Tel+Cal-dob group than in Tel group(P<0.05).After 3,6 and 12 months of treatment,the conversion rates of dipper blood pressure were higher in Tel+Cal-dob groupthan in Tel group(P<0.05).There was no significant difference in the incidence of adverse effects between the two groups(P>0.05).Conclusion Telmisartan combined with calcium dobesilate is effective in the treatment of patients with non-dipper hypertension complicated with T2DM.

Objective:To analyze the dietary patterns of Chinese adults and explore the relationship with serum uric acid (SUA) and hyperuricemia (HUA).Methods:A total of 9 358 adults were selected in the 2018 China Health and Nutrition Survey. Dietary intake data were collected by three consecutive 24-hour dietary recalls and weighing method. The social demographic information of the survey subjects was obtained through questionnaire surveys. The dietary patterns were extracted using factor analysis, and the relationship between dietary patterns and SUA was analyzed using multiple linear regression analysis. The correlation between HUA and dietary patterns was analyzed using logistic regression analysis models.Results:Four dietary patterns were identified: northern (high intakes of wheat, other cereals,and tubers); modern (high intakes of fruit, dairy, eggs, and nuts); southern (high intakes of rice and vegetables);animal food-wine (high intake of organ meats, seafood, and wine). The multiple linear regression analysis results showed that the northern pattern was negatively correlated with SUA ( β=-0.438, 95% CI: -0.500--0.376); the modern pattern was negatively correlated with SUA ( β=-0.134, 95% CI: -0.219--0.049); the southern model was significantly correlated with higher SUA ( β=0.146, 95% CI: 0.079-0.214); the animal food-wine pattern was positively correlated with SUA ( β=0.188, 95% CI: 0.123-0.252). Logistic regression analysis showed that compared with the northern model score Q1 group, the risk of developing HUA was reduced in Q3 and Q4 groups, with ORs values of 0.777 (95% CI: 0.650-0.929) and 0.509 (95% CI: 0.423-0.613), respectively; and compared with the modern model score Q1 group, the higher the scores in Q3 and Q4 groups, the HUA was lower, with ORs of 0.793 (95% CI: 0.660-0.953) and 0.768 (95% CI: 0.631-0.934), respectively. Compared with the animal food-wine pattern score Q1 group, the risk of developing HUA was increased in both Q3 and Q4 groups ( Q3 group: OR=1.224, 95% CI: 1.012-1.480; Q4 group: OR=1.312, 95% CI: 1.086-1.584). Conclusions:Dietary patterns are associated with HUA. The northern and modern patterns are related to lower SUA levels and reduced risk of HUA, while the animal food-wine pattern increases the risk of HUA.