ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Purpose To investigate the clinicopathological features and cytogenetic characteristics in the fumarate hydratase(FH)-deficient uterine smooth muscle tumors.Methods A total of 334 paraffin-embedded specimen of be-nign,borderline,and malignant uterine smooth muscle tumors were collected.FH-deficient uterine smooth muscle tumors were screened using the immunohistochemical detection with FH and S-(2-succino)-cysteine(2SC)antibodies.A retrospective analysis of the clinicopathological features and FH mutations was conducted.Results Compared with the 310 non-FH-deficient uterine leiomyomas(non-FH-dUL),14 cases(93.3％)out of the 15 FH-dUL presented with staghorn blood vessels(x2=52.86,P＜0.000 1),8 cases(53.3％)exhibited pulmonary edema-like stroma(x2=26.41,P＜0.000 1),8 cases(53.3％)had cytoplasmic eosinophilic globules(x2=41.85,P＜0.000 1),5 cases(33.3％)showed multifocal bizarre nuclei(x2=72.54,P＜0.000 1),5 cases(33.3％)had large eosino-philic nucleoli with viral inclusion-like halos(x2=38.85,P＜0.000 1),and 5 cases(33.3％)demonstrated a sig-nificant increase in cell density(x2=8.782,P=0.003).The above morphological features were also observed in a case of FH-d uSTUMP and FH-d uLMS.Among the 14 cases with follow-up,except for one death in the FH-d uLMS,none reported the renal cell carcinoma and cutaneous leiomyoma.FH mutations were identified in 11 cases and the hotspot mutations were found in exon 1,2,4,5,6 and 7.Among these variations,c.125C＞T,c.151C＞T and c.704A＞C were found to be the hotspot gene variations.Furthemore,7 gene variations(c.197A＞G,c.426G＞T,c.505C＞T,c.704A＞C,c.812A＞C,c.847T＞C,c.1006A＞G)were not included in COSMIC and ClinVar database and were supposed to be novel.Conclusion The combination of FH/2SC immunohistochemical detection and FH exon mutation analysis are reliable tools for the early identification of FH-deficient uterine smooth muscle tumors or hereditary leiomyomatosis and renal cell carcinoma(HLRCC)syndrome.

Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

Objective:To investigate the clinical significance of CD105 and erythropoietin-producing hepatocellular receptor A2 (EPHA2) expressions in breast invasive ductal carcinoma and the effects of the combination of diabetes mellitus on CD105 and EPHA2 expressions.Methods:A retrospective case series study was conducted. A total of 74 patients with breast invasive ductal carcinoma in Affiliated Hospital of Jiangsu University from June 2019 to June 2024 were selected, and paraffin specimens from the patients after surgery were collected. Immunohistochemistry SP method was used to detect the expressions of CD105 and EPHA2 proteins in specimens. CD105 expression was expressed as the number of CD105 labeled microvessels, and EPHA2 expression was expressed as the proportion of EPHA2 positive expression area. The correlation of CD105 and EPHA2 expressions with the clinicopathological characteristics and diabetes mellitus of patients, as well as the relationship between the expressions of CD105 and EPHA2 were analyzed. Cox proportional hazards model was used to make univariate and multivariate analysis of the factors influencing overall survival of patients.Results:All 74 patients were female. The median age was 60 years old, 44 patients (59.46%) had tumor grade ≥ grade 3, 36 patients (48.65%) had tumor diameter ≥ 2 cm, 28 patients (37.84%) had lymph node metastasis, 30 patients (40.54%) had nerve vessel invasion, and 32 patients (43.24%) had diabetes mellitus. There were statistically significant differences in the proportion of patients with different age, tumor diameter, TNM stage, lymph node metastasis or not and nerve vessel invasion or not between diabetes mellitus group and non-diabetes mellitus group (all P < 0.05). The number of CD105 marking the microvessel was (32±9) and (24±8), respectively in diabetes mellitus group and non-diabetes mellitus group, and the difference was statistically significant ( t = 3.63, P < 0.010); the positive expression area proportion of EPHA2 was (19±5)% and (15±4)%, respectively, and the difference was statistically significant ( t = 3.85, P < 0.010). The expression of CD105 was related to the duration of diabetes mellitus, tumor diameter, TNM stage and lymph node metastasis or not (all P < 0.05), and the expression of EPHA2 was related to tumor diameter and TNM stage (all P < 0.05). Pearson correlation analysis showed a positive correlation between CD105 and EPHA2 expression ( r = 0.75, P < 0.001). The differences in overall survival of patients with or without diabetes mellitus and patients with different CD105 and EPHA2 expressions were statistically significant (all P < 0.05). Multivariate analysis showed that CD105 expression ( HR = 1.10, 95% CI: 1.04-1.16, P = 0.001) and EPHA2 expression ( HR = 1.35, 95% CI: 1.10-1.66, P = 0.005) were independent factors influencing the overall survival of patients with breast invasive ductal carcinoma. Conclusions:The expressions of CD105 and EPHA2 are independent prognostic factors in patients with breast invasive ductal carcinoma, and diabetes mellitus can promote the expressions of CD105 and EPHA2, which may increase the risk of poor prognosis.

Objective:To explore the feasibility and adaptability of laparoscopy in the surgical treatment of splenic aneurysm.Methods:The data of 28 patients with splenic aneurysms who underwent laparoscopic surgery in the Department of Hepatobiliary and Pancreatic Surgery of the Third Affiliated Hospital of Soochow University from January 2010 to December 2023 were retrospectively collected and analyzed. Among them, there were 13 males and 15 females, with the age of (57.3±7.7) years. All patients underwent laparoscopic splenic aneurysm resection, and whether to perform splenic artery anastomosis or splenectomy was determined based on the intraoperative situation. Collect the long diameter and location of splenic aneurysms, intraoperative blood loss, operation time, postoperative complications (bleeding, pancreatic fistula, splenic infarction, and splenic vein and portal vein thrombosis), postoperative hospital stay and hospitalization expenses of the patients.Results:All patients successfully underwentlaparoscopic surgery for splenic aneurysms. Aneurysms were located at the origin of the splenic artery in 3 cases (10.7%), in the middle in 8 cases (28.6%), and at the tail in 17 cases (60.7%). The long diameter of the aneurysms was (3.1±1.7) cm. Among the 28 patients, 18 cases (64.3%) underwent splenic aneurysm resection alone, 5 cases (17.9%) underwent splenic aneurysm resection combined with end-to-end anastomosis of the splenic artery, and 5 cases (17.9%) underwent splenic aneurysm resection combined with splenectomy. The operation time of 28 patients was (124.3±55.1) min, the intraoperative blood loss was 100.0 (50.0, 162.5) ml, the postoperative hospital stay was (10.9±3.8) days, and the hospitalization cost was (3.7±1.2) wanyuan. Among the 28 patients, 5 cases (17.9%) developed pancreatic fistula, 1 case (3.6%) had partial splenic infarction, and 1 case (3.6%) had portal vein and splenic vein thrombosis after the operation.Conclusion:Laparoscopic surgery for splenic aneurysm is safe and feasible, with less surgical trauma and quick postoperative recovery.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.