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.

Objective To systematically analyze the clinical advantageous diseases and core acupoint combinations of Jin's Three-Needle Therapy,providing data support for its broader clinical application.Methods The relevant literature from the China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database,VIP Chinese Sci-Tech Journal Database,and China Biology Medicine(CBM)database were retrieved,covering all publications since the establishment of Jin's Three-Needle Therapy.A database of acupoint combinations was constructed,and statistical analyses were performed using SPSS Modeler,Cytoscape,Review Manager,Stata,and R software to evaluate literature quality,sensitivity,disease spectrum,therapeutic efficacy,high-frequency acupoint combinations,association rules,and combined therapies.Results A total of 228 eligible studies were included.The results indicate that Jin's Three-Needle Therapy has been applied to 11 disease categories and 63 specific conditions,with post-stroke hemiplegia and autism spectrum disorder identified as its primary advantageous diseases.The Temporal Three-Needle and Four-Spirit Needle emerged as the core acupoint combinations.The overall clinical efficacy rate reached 91.1％,and the therapy was frequently combined with rehabilitation training.Conclusion The unique three-needle prescription pattern of Jin's Three-Needle Therapy demonstrates significant clinical advantages.However,potential publication bias may exist,and further exploration is needed to elucidate its mechanisms and optimize clinical efficacy.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.

Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.Methods Twenty-four adult male SD rats were randomized equally into normal control group,high-glucose and high-fat feeding group,streptozotocin(STZ)-induced diabetic model group,and quercetin treatment(daily dose 100 mg/kg)group.Pathological changes of the renal tissues of the rats were observed with HE staining,serum inflammatory factor levels were determined with ELISA,and renal expression of NF-κB was observed by immunohistochemistry.Fast blood glucose(FBG),serum levels of triglyceride(TG),BUN,and Scr,and 24-h urine protein content of the rats were measured,and renal expressions of HMGB1,RAGE,NF-κB,Bax,Bcl-2,and caspase-3 were detected with Western blotting.Results The diabetic rats showed significantly increased levels of FBG,TG,BUN,and Scr,renal hypertrophy index,24-h urinary protein content,serum IL-1β,IL-6 and TNF-α levels and renal expressions HMGB1,RAGE,NF-κB,Bax,and caspase-3 with decreased renal expression of Bcl-2.All these changes were significantly alleviated by quercetin treatment of the rats.Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.Methods Twenty-four adult male SD rats were randomized equally into normal control group,high-glucose and high-fat feeding group,streptozotocin(STZ)-induced diabetic model group,and quercetin treatment(daily dose 100 mg/kg)group.Pathological changes of the renal tissues of the rats were observed with HE staining,serum inflammatory factor levels were determined with ELISA,and renal expression of NF-κB was observed by immunohistochemistry.Fast blood glucose(FBG),serum levels of triglyceride(TG),BUN,and Scr,and 24-h urine protein content of the rats were measured,and renal expressions of HMGB1,RAGE,NF-κB,Bax,Bcl-2,and caspase-3 were detected with Western blotting.Results The diabetic rats showed significantly increased levels of FBG,TG,BUN,and Scr,renal hypertrophy index,24-h urinary protein content,serum IL-1β,IL-6 and TNF-α levels and renal expressions HMGB1,RAGE,NF-κB,Bax,and caspase-3 with decreased renal expression of Bcl-2.All these changes were significantly alleviated by quercetin treatment of the rats.Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

Objective To analyze the emergency treatment protocols and nursing measures for patients with diquat and paraquat poisoning,aiming to provide references for updating future clinical practice.Methods A retrospective study was conducted involving 53 patients with diquat and paraquat poisoning admitted to the department of emergency of the First Affiliated Hospital of Wenzhou Medical University from January 1,2019,to December 31,2023.The patients were divided into survival and death groups based on their prognosis.Clinical data were collected to compare organ dysfunction,the proportion of hemoperfusion(HP),average number of HP sessions,the proportion of blood purification,average duration of blood purification,and the proportion of HP combined with continuous renal replacement therapy(CRRT)between two groups of patients with different prognoses.Results Among the 53 patients,27(50.94%)were male and 26(49.06%)were female;with an age range of 14 to 86 years and a mean age of(38.13±19.68)years.Fifty-two cases were due to intentional ingestion,and 1 was accidental.The detected blood concentrations of diquat ranged from 57.38 to 119762.00 μg/L,while those of paraquat ranged from 60.12 to 71 244.89 μg/L.Forty patients developed multiple organ dysfunction syndrome(MODS),with 38 ultimately progressing to multiple organ failure,primarily affecting the gastrointestinal tract,kidneys,and liver.After aggressive treatment and nursing,the blood concentrations of 13 patients(24.53%)dropped below 50 μg/L,and they were discharged after 4 to 34 days of hospitalization.Thirty-two patients'families opted for withdrawal of treatment and discharge,with subsequent confirmation of death after follow-up,hospital stay:1-4 days.Eight patients died in-hospital,hospital stay:1-3 days,resulting in a total mortality rate of 40 cases(75.47%).Compared to the survival group,the death group had significantly higher rate of neurological,renal,respiratory,and liver injuries[neurological:90.00%(36/40)vs.15.38%(2/13),renal:95.00%(38/40)vs.69.23%(9/13),respiratory:97.50%(39/40)vs.30.77%(4/13),liver injury:85.00%(34/40)vs.46.15%(6/13),all P<0.05].Furthermore,the death group had significantly lower average number of HP sessions and average duration of blood purification compared to the survival group[average number of HP sessions:4.35±2.42 vs.6.62±1.17,average duration of blood purification time(days):1.53±1.09 vs.5.23±3.90,both P<0.05].Conclusions Poisoning with a mixture of diquat and paraquat is life-threatening and associated with a high mortality.In addition to systematic treatment,individualized and dynamic nursing support should be provided,including close monitoring of the manifestations and laboratory indicators of affected organ systems.Therefore,optimization treatment protocols during the peak mortality period may help reduce mortality in patients with diquat and paraquat poisoning.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

OBJECTIVE To explore the influential factors for “Internet +” prescription circulation and construction specifications of prescription circulation platform， so as to provide reference for the government to formulate relevant policies and standardized construction of prescription circulation platform. METHODS Stakeholders in the process of prescription circulation service in medical institutions in Sichuan province were selected to conduct key insider interviews， and grounded theory was used to analyze the data. RESULTS The influential factors of prescription circulation could be divided into three aspects： participant factor， administrative decision factor and information technology factor. The influential factors of prescription circulation mainly lay in pharmacy admission and withdrawal mechanism， medical insurance reimbursement service， supporting policies and pharmaceutical care ability. In terms of pharmacy admission and withdrawal mechanism， pharmacy qualification， pharmaceutical service personnel， drug allocation and distribution should be considered to unify pharmacy admission standards； in terms of medical insurance reimbursement service， it should actively connect with social pharmacies to realize the transfer of prescription medical insurance reimbursement from designated pharmacies； in terms of supporting policies， it should pay attention to the construction of the top-level design of prescription circulation； in terms of pharmaceutical care ability， regular training and assessment of licensed pharmacists should be performed in drug consultation， prescription review and other pharmaceutical care. CONCLUSIONS Participants have more influence on prescription circulation， and pharmacy admission and withdrawal mechanism and pharmaceutical care ability need to be improved. There are various types of prescription circulation platform construction， but each has its own advantages and disadvantages. It is suggested that relevant government departments should improve the access threshold of pharmacies， follow up medical insurance reimbursement services and supporting policies， and explore ways to improve pharmaceutical care capacity， leading and issuing relevant policies and measures to promote the prescription circulation service and make the “Internet +” prescription circulation develop in an orderly manner.

【Objective】 To compare the supply data of red blood cells(RBCs) from 18 blood centers in China before and after the outbreak of COVID-19 during 2018 to 2021. 【Methods】 Eight indicators related to RBCs supply from 18 blood centers in China during 2018-2021 were collected retrospectively, including the storage of total amount of qualified RBCs (referred to as the total amount of storage), the distribution of total amount of RBCs (referred to as the total amount of distribution), the distribution amount of RBCs per 1 000 population (referred to as the amount of distribution per 1 000 population), the distribution amount of RBCs from 400 mL original blood per 1 000 population [referred to as the amount of distribution per 1 000 population (400 mL)], the average daily distribution amount of RBCs (referred to as the average daily distribution amount), the average daily storage amount of RBCs (referred to as the average daily storage amount), the average storage days of RBCs when distribute (referred to as the RBC storage days), and the expired amount of RBCs (referred to as the expired amount). Based on the outbreak time of COVID-19, the data of 2018 and 2019 were the pre-pandemic group, and the data of 2020 and 2021 were the post-pandemic group. 【Results】 Data on RBCs supply in 18 blood centers from 2018 to 2021(comparison of the pre-pandemic group and the post-pandemic group): the amount of distribution per 1 000 population (median 14.68 U>13.92 U) decreased, the amount of distribution per 1 000 population (400 mL) (median 10.16 U>9.21 U) decreased, and the difference was statistically significant (P<0.05); data comparison between 2019 and 2020:the total amount of distribution (median 117 770.38 U>99 084.08 U) decreased, the amount of distribution per 1 000 population (median 15.04 U>12.19 U) decreased, the amount of distribution per 1000 population (400 mL) (median 10.11 U>8.94 U), the average daily distribution amount(322.66 U>270.73 U) decreased and RBC storage days (median 10.50 d<11.45 d) increased, the difference has statistical significance (P<0.05); data comparison between 2020 and 2021:the total amount of storage (median 101 920.25 U<120 328.63 U), the total amount of distribution (median 99 084.08 U<118 428.62 U), the amount of distribution per 1 000 population (median 12.19 U<15.00 U), the amount of distribution per 1 000 population (400 mL) (median 8.94 U<9.46 U), the average daily distribution amount (270.73 U>324.46 U), the average daily inventory (median 3 222.00 U<4 328.00 U) increased, the expired amount (median 1.50 U>0.00 U) decreased, the difference has statistical significance (P<0.05). The results of ANOVA showed that there were significant differences on the data related to RBCs supply (except expired amount) in different blood centers (P<0.05). The ratio of average daily stock to average daily distribution in the post-outbreak group (median 12.36 d) was higher than that in the pre-outbreak group (median 10.92 d), the difference has statistical significance (P<0.05), with significant difference among different blood centers (P <0.05). 【Conclusion】 The COVID-19 pandemic has a significant impact on RBCs supply in different blood centers. In the second year of the pandemic, the supply capability had recovered to some extent, and there were differences in RBCs supply in different blood centers.

Objective To explore the early predictors of the development of the novel coronavirus infection(COVID-19)into severe and critical forms.Methods COVID-19 patients hospitalized in the Department of Intensive Care Medicine,Infection ward,Respiratory and Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as the study objects,and were divided into mild/medium group,severe group,and critical group according to the severity of illness during hospitalization.General clinical data and early laboratory results of the three groups were collected and compared.Results A total of 242 patients with novel coronavirus infection were included,including 117 mild/medium patients,55 severe patients,and 70 critically severe patients.There were 165 males and 77 females with a median age of 70(59,80)years.The age,sex,diabetes,heart disease,stroke,combined pneumonia,combined bloodstream infection,APACHE Ⅱ score,respiratory rate on admission,systolic blood pressure,and early white blood cell count(WBC),lymphocyte count(LYM),urea,creatinine,albumin,C-reactive protein,D-dimer,interleukin-6(IL-6),and calcium reduction of patients in the three groups had significant(all P<0.05).Ordered logistic regression shows,previous heart disease,stroke,combined bloodstream infection,WBC,high IL-6 level,and low LYM level were independent risk factors for severe and critical COVID-19 infection[odds ratio(OR)and 95%confidence interval(95%CI)were 3.253(1.694～6.246),5.251(2.378～11.592),respectively.6.920(2.499～19.189),1.111(1.041～1.186),1.003(1.001～1.006),0.571(0.353～0.926)].ROC curve analysis showed that WBC,LYM,IL-6 and their combined detection had certain predictive value for the severity of COVID-19(all P<0.05),and the combined detection of WBC,LYM and IL-6 had better predictive value than a single indicator(P<0.05).Conclusion Previous heart disease,cerebrovascular disease,early combination of bloodstream infection,high levels of IL-6,white blood cell count,and low lymphocyte levels at admission were independent risk factors that helped to predict the severity of COVID-19 infection early.The combined detection of WBC,LYM and IL-6 has certain predictive value for the development of severe and critical COVID-19.