ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

Objective:To explore application value of observed tumor enhancement characteristics by dynamic enhancement magnetic resonance imaging(MRI)in assessing blood supply of small hepatocellular cancer.Methods:The cases data of 80 patients with suspected small hepatocellular cancer who admitted to Yichang Central People's Hospital from January 2019 to January 2023 were retrospectively analyzed.The enhancement characteristics of tumors of all patients were real-timely observed by MRI scanner,which included the relative enhancement degree(RSI),enhancement mode,time-signal intensity curve,etc.The enhanced characteristics of the tumors were recorded,which were combined with a series of variables included disease history,tumor type,tumor size,the number of tumor,liver function status of patients to conduct analysis.The receiver operating characteristics(ROC)curve was adopted to analyze the application value of the observed tumor enhancement characteristics by dynamic enhancement MRI in assessing the status of blood supply of small hepatocellular cancer.Results:There were statistically significant differences in the RSI(F=40.151,P＜0.05),enhancement degree(x2=27.374,P＜0.05),and time-signal intensity curve(x2=20.950,P＜0.05)of dynamic enhanced MRI among different stages of small hepatocellular cancer.The differences in medical history(F=17.844,P＜0.05),tumor type(x2=11.219,P＜0.05),tumor size(x2=14.081,P＜0.05),and the number of tumor(x2=74.310,P＜0.05)among different enhancement degrees of arterial phase were also statistically significant.With the enhancement degree increased,the asymptomatic period increased,and the number of malignant tumors increased,and tumor size increased.The differences in liver function status among different time-signal intensity curves were statistically significant(F=330.182,325.872,216.689,P＜0.05).The area under curve(AUC)value of the ROC of the RSI of observed tumor enhancement characteristics by dynamic enhancement MRI was 0.582(95％CI:0.493-0.670)in assessing blood supply of small hepatocellular cancer.Conclusion:Dynamic enhancement MRI can observe the vascular generation and hemodynamic changes of small hepatocellular cancer,which has a certain application value in assessing blood supply of small hepatocellular cancer,and it can help doctors to choose appropriate treatment plan and assess treatment effect.

Objective:To study the effect of tertiary lymphoid structures(TLS)on the pathological response and prognosis of patients with non-small cell lung cancer(NSCLC)receiving neoadjuvant therapy.Methods:We retrospectively collected the data of 132 patients with NSCLC who underwent neoadjuvant therapy and surgery at Tianjin Chest Hospital between January 2019 and December 2023,including 40 in the neoadjuvant chemotherapy(NC)group and 92 in the NC plus immunotherapy(NCI)group.The percentage of residual viable tumor(RVT)and tumor infiltrating lymphocyte(TIL)counts were evaluated by hematoxylin and eosin(H&E)staining,while TLS number and matur-ity were assessed by H&E and immunohistochemical staining.The differences in TLS number and maturity and effects on patient pathologic-al response and prognosis were compared between groups.Results:TIL count,total TLS number,pathological complete response and major pathological response rates were significantly higher in the NCI versus NC group(P<0.001).Moreover,a multivariate Logistic analysis sho-wed that TLS number and maturity and TIL count affected pathological response in the NCI group(P<0.05).A multiple linear regression ana-lysis indicated that a low TIL count was a risk factor for a high RVT in the NC group,while a low number of mature TLS,low TIL count,and N stage were independent risk factors for a high RVT in the NCI group(all P<0.05).In the NCI group,a multivariate Cox regression analysis showed that a low number of mature TLS(P=0.001)and low TIL count(P=0.009)were independent predictors of disease-free survival(DFS),while a survival analysis showed that patients in the NCI group with high(vs.low)numbers of mature TLS and a high(vs.low)TIL count had significantly longer DFS(all P<0.001).Conclusions:A low number of mature TLS and low TIL count were associated with an adverse patholo-gical response and short DFS in patients with NSCLC.Thus,TLS maturity and TIL count can predict the pathological response and prognosis of patients with NSCLC treated with NCI.

Objective To establish the reference intervals for test indicators of thyroid function,namely thyroid stimulating hormone(TSH),free thyroxine(FT4),and free triiodothyronine(FT3),in the children aged 0 to 15 years old in Nanning,China.Methods A total of 1 289 healthy children aged 0 to 15 years old who attended the Guangxi International Zhuang Medicine Hospital Affiliated with Guangxi University of Chinese Medicine from October 2018 to August 2023 were selected.The concentrations in serum TSH,FT4,and FT3 were measured by chemiluminescent microparticle immunoassay(CMIA).According to the Clinical and Laboratory Standards Institute(CLSI)EP28-A3c guideline,the nonparametric percentile method was used to establish the reference intervals for TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area.Results The established reference intervals were as follows:TSH(male):0 to＜1 month:0.88-7.81 μIU/mL,1 month to 15 years:0.59-5.06 μIU/mL;TSH(female):0 to＜1 month:0.93-8.42μIU/mL,1 month to 15 years:0.60-4.30 μIU/mL.FT4(male):0 to＜1 month:0.99-1.92 pg/mL,1 month to 15 years:0.86-1.33 pg/mL;FT4(female):0 to＜1 month:1.05-2.06 pg/mL,1 month to 15 years:0.85-1.37 pg/mL;FT3:0 to＜1 month:2.16-4.24 pmol/L,1 month to＜11 years:2.75-4.49 pmol/L,11 to 15 years:2.45-4.34 pmol/L.Significant differences were observed among different gender and age groups for TSH,FT4,and FT3 levels(P＜0.05).Conclusion This study successfully established the refer-ence intervals of TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area,which were significantly different among various gender and age groups.

Objective:To investigate the expression level of NME3 in gastric cancer and its correlation with clinicopathological characteristics and prognosis.Methods:A retrospective case series study was conducted. The clinicopathological data of 156 patients with gastric cancer who received radical gastrectomy in Zhejiang Cancer Hospital between January 2013 and December 2017 were collected. The samples of cancer tissues and paracancerous tissues were taken and partial paracancerous tissues were not meet the standard. Finally, immunohistochemical staining was conducted on both cancer tissues (156 cases) and paracancerous tissues (139 cases) to detect the expression of NME3 protein; H scoring system was used to score the expression of NME3 protein and the patients were divided into NME3 high expression group (H score ≥ 6 points) and NME3 low expression group (H score < 6 points). The clinicopathological characteristics of the 2 groups were analyzed. Kaplan-Meier method was used for overall survival (OS) analysis of the 2 groups, and log-rank test was used for comparison. Univariate and multivariate Cox proportional risk models were used to determine the poor independent factors affecting the poor OS in patients with gastric cancer.Results:The median age of the 156 patients was 61 years (53 years, 68 years), including 110 males (70.5%) and 46 females (29.5%). The proportion of patients with NME3 high expression in cancer tissues was lower than that in paracancerous tissues [51.9% (81/156) vs. 75.5% (105/139)], and the difference was statistically significant ( χ2 = 17.60, P < 0.001). The proportion of patients with NME3 high expression in moderate-low differentiation and moderate differentiation group was lower than that of those in low-differentiation group [63.3% (50/79) vs. 39.4% (28/71)], the proportion of patients with NME3 high expression in pTNM staging group Ⅲ-Ⅳ was higher than that of those in pTNM staging group Ⅰ-Ⅱ [55.5% (76/137) vs. 26.3% (5/19)], and the difference was statistically significant (both P < 0.05). The proportion of patients with NME3 high expression was 62.2% (46/74), 52.0% (13/25), 39.3% (22/56), respectively in patients with Lauran intestinal type, mixed type and diffused type, and the differences were statistically significant ( χ2 = 6.69, P = 0.035). In addition, OS of patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the difference was statistically significant ( P < 0.001). The further analysis of gender subgroup showed that OS of male patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and OS of female patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the differences was statistically significant (all P < 0.05). Univariate and multivariate Cox regression analysis showed that the expression of NME3 in cancer tissues (high expression vs. low expression: HR = 0.342, 95% CI: 0.207-0.564, P < 0.001), family history (yes vs. no: HR = 2.240, 95% CI: 1.285-3.907, P = 0.004), pN staging (N 2-3vs. N 0-1: HR = 2.133, 95% CI: 1.114-4.083, P = 0.022), pM staging (M 1vs. M 0: HR = 2.761, 95% CI: 1.386-5.500, P = 0.004), carcinoma embryonic antigen (CEA) level (CEA > 5 ng/ml vs. CEA ≤ 5 ng/ml: HR = 1.688, 95% CI: 1.018-2.798, P = 0.042), carbohydrate antigen 125 (CA125) level (CA125 > 35 U/ml vs. CA125 ≤ 35 U/ml: HR = 2.913, 95% CI: 1.403-6.047, P = 0.004) were independent factors influencing OS in patients with gastric cancer. Conclusions:NME3 is lowly expressed in gastric cancer tissues, and it is highly expressed in higher-differentially, late staged and intestinal type gastric cancer. NME3 low expression is an independent risk factor for the poor prognosis of gastric cancer. It is speculated that NME3 may play a inhibitory role in gastric cancer.

Objective The clinical value of serum VILIP-1 and Hepc25 in predicting the prognosis of patients with Acute ischemic stroke(AIS)from intravenous thrombolysis was analyzed.Methods A total of 225 patients with acute ischemic stroke diagnosed and treated in the hospital from January 2022 to November 2023 were selected.According to Rankin Scale(mRS)grouping study,97 patients with mRS≥3 were divided into poor prognosis group and 128 patients with mRS<3 were divided into good prognosis group.The serum levels of VILIP-1 and Hepc25 were compared and their prognostic value for intravenous thrombolysis.Results After logistic regres-sion analysis,age,admission blood glucose,LYM,NIHSS score,PLT,WBC,VILIP-1,and Hepc25 were all factors affecting the prognosis of AIS patients(P<0.05);VILIP-1 and Hepc25 levels increased in patients with moderate and severe defects compared with mild defects.VILIP-1 and Hepc25 levels were higher in patients with severe defects than those with moderate defects.Compared with the poor prognosis group,the VILIP-1 and Hepc25 levels in the good prognosis group were decreased,with statistical difference(P<0.05).ROC curve analysis showed that single diagnosis of VILIP-1 and Hepc25 was lower than combined diagnosis(P<0.05).Conclusion The elevated levels of VILIP-1 and Hepc25 participate in the process of intravenous thrombolysis and affect the prognosis of patients,and can be used as clinical indicators for the prognosis of AIS patients.

ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis"， this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine （TCM）， predict their efficacy， and obtain the core prescriptions for treating tremors in TCM， providing references for clinical application and new drug development. MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure （CNKI） were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System （V3.0） was used to analyze and explore the medication rules including drug frequency， properties， flavor， meridian tropism， and pharmacological effects， as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions， prestigious doctors' medical cases， and network analysis results， the priority level of the developed prescriptions was determined through comprehensive evaluation. ResultA total of 81 ancient prescriptions were screened， involving 246 drugs， and 171 prescriptions were screened from prestigious doctors' medical cases， involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor， mainly acting on the liver， spleen， and kidney meridians. In terms of efficacy， they were mainly effective in tonifying deficiency， soothing liver and extinguishing wind， activating blood and resolving blood stasis， clearing heat， and resolving exterior. Through association rules and K-means clustering， the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix， Atractylodis Macrocephalae Rhizoma， Angelicae Sinensis Radix， Poria， Gastrodiae Rhizoma， and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood， with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases， as well as multi-target drug efficacy prediction， showed that Combination 1 had the highest disturbance score on the disease network. Furthermore， comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases， indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison， Combinations 3， 2， and 4 were less utilized in contemporary clinical practice， with lower rankings in network disturbance scores， suggesting that their development value still warranted further exploration. ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver， spleen， and kidney. In line of syndrome differentiation， drugs potent in soothing liver， extinguishing wind， activating blood， and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Astragali Radix， Poria， and Atractylodis Macrocephalae Rhizoma （combination 1） have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.

ObjectiveTo explore the mechanism of Naoxintong capsules' intervention in cerebral ischemia-reperfusion by building a mouse cerebral ischemia-reperfusion model based on short-chain fatty acids. MethodC57BL/6J male mice were randomly divided into the sham group， model group， Naoxintong group （158.9 mg∙kg^-1）， and Ginaton group （12.1 mg∙kg^-1） according to the random number table method. The model of cerebral ischemia-reperfusion （MCAO/R） was prepared via the filament occlusion method. The effect of Naoxintong capsules on brain injury in MCAO/R mice was evaluated by the neuroethological score， cerebral infarction area determination， Nissl staining， and immunofluorescence staining. Hematoxylin-eosin （HE） staining and Western blot were employed to evaluate the effect of Naoxintong capsules on the intestinal barrier in MCAO/R mice. The content of short-chain fatty acids in mouse feces was detected by LC-MS/MS. ResultCompared to the sham group， the model group exhibited significant increases in the cerebral infarction area， neuroethological score， and cell apoptosis rate （P<0.01）， with a notable decrease in the number of Nissl bodies （P<0.01）. The protein expression levels of Claudin-1 and Occludin were significantly reduced （P<0.05）. Compared with the model group， the intervention of Naoxintong capsules significantly decreased the cerebral infarction area （P<0.05） and improved the neuroethological score （P<0.01） and cell apoptosis rate （P<0.01）， with the number of Nissl bodies （P<0.01） and expression levels of Claudin-1 and Occludin proteins （P<0.01） increased. LC-MS/MS results showed that compared to the sham group， the model group featured a significantly reduced content of acetic acid， propionic acid， and butyric acid in feces （P<0.01）， while valeric acid， isovaleric acid， and isobutyric acid levels were increased （P<0.01）. The intervention of Naoxintong capsules notably lowered the content of valeric acid， isovaleric acid， and isobutyric acid （P<0.01）. ConclusionNaoxintong capsules can improve brain and intestinal barrier damage and play a protective role in cerebral ischemia-reperfusion by regulating the content of short-chain fatty acids.

Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.