Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

The experience of professor YANG Wen-Hui in treating lumbago disease with YANG's Baliao-acupoints moxibustion is introduced in this paper.YANG Wen-Hui believes that the basic pathogenesis of lumbago disease is'cold causes lower back pain',and based on the philosophical idea of'harmony in Shushu(the ways to cultivate health)',he proposes'YANG's Baliao-acupoints moxibustion'for the treatment of lumbago disease.According to the patient's condition,professor YANG used the acupoints of Shangliao(BL31),Ciliao(BL32),Zhongliao(BL33),and selected the moxa cone like jujube core,soybean or wheat grain,and applied moxibustion with the technique of'San Yang Kai Tai'or'Ruo feng Chui Yun',the number of moxibustion is proportional to the age of the patient.YANG's Baliao-acupoints moxibustion in treating lumbago disease exerts highly and remarkable clinical efficacy,and it was widely acclaimed by the patients.

Objective:To investigate the effect of Early infarct growth rate(EIGR) on the prognosis of patients with acute large vessel occlusive ischemic stroke.Methods:A total of 164 patients with acute large vessel occlusive ischemic stroke were enrolled in the emergency department of the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to December 31, 2022.According to the change of the National Institutes of Health Stroke Scale (NIHSS) score at admission and 72 h after treatment, the patients were divided into good prognosis group and poor prognosis group. The basic clinical data of the two groups were observed and compared. The risk factors of poor prognosis were analyzed by univariate regression. The effect of EIGR on prognosis after age stratification was further analyzed.Results:Comparing the clinical data of the two groups, there was no difference in EIGR (mL/h) (7.67 vs. 8.24, P=0.211) between the two groups. The product between EIGR and age was included as the interaction term, and the result of the interaction term in the model was statistically significant ( OR=1.002, 95% CI: 1.000-1.003, P=0.032) .Moreover, the result was still statistically significant after adjusting for relevant variables (gender, history of hypertension, history of atrial fibrillation, history of diabetes, history of coronary heart disease, and history of stroke) ( OR=1.002, 95% CI:1.000-1.003, P=0.027). Subgroup analysis was performed according to the median age (71 years). In the elderly group, the proportion of poor prognosis was higher with fast core infarction growth rate defined by 25 mL/h and 15 mL/h ( P < 0.05).In the younger age group, there was no significant difference in the proportion of poor prognosis in the fast core infarction growth rate compared with the slow type ( P > 0.05). Conclusions:EIGR can predict the early clinical outcome early in elderly patients with large vessel occlusive ischemic stroke.

Objective To develop a low-oxygen mixed gas generator to make up for the deficiencies of low-pressure chambers and load-resistant hypoxia trainers during pilot hypoxia tolerance testing.Methods The device prepared the low-oxygen gas with the principle of gas separation,which was composed of a Sunsource OLF1100D-220AF air compressor,a SMC IDG75SAM4-03 filter,a buffer tank,an AIR Products PA3010 integrated assembly,a control box,sensors and regulators.The sensors included the pressure sensor,flow sensor,concentration sensor and dew point temperature sensor,and the control box consisted of a main control board,a power supply module,a transmission module,a communication module,a display and a housing.The embedded control software of the device was developed with KEIL 5 and C++.Results The device developed prepared the low-oxygen gas with the volume fraction being 4％to 18％and the maximum error of volume fraction being 0.05％,and the main components of the prepared gas met the technical requirements of medical oxygen as stipulated in GB 8982-2009 Oxygen supplies for medicine and aircraft breathing.Conclusion The low-oxygen gas prepared by the device has its volume fraction precisely controlled and can be used for hypoxia tolerance testing and acclimation training for pilots.[Chinese Medical Equipment Journal,2024,45(7):24-28]

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G₀/G₁ phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Flavonoids/pharmacology* ; Colonic Neoplasms/prevention & control* ; Animals ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Mice ; Mice, Inbred BALB C ; Cell Movement/drug effects* ; Humans ; Gene Expression Regulation, Neoplastic/drug effects* ; Cell Cycle Checkpoints/drug effects*

Objective:To investigate the efficacy of endoscopic histoacryl injection in cirrhotic patients with newly-developed esophagogastric varices (EGV) who have previously undergone splenectomy combined with pericardial devascularization.Methods:From January 2015 to January 2020, 125 cirrhotic patients with EGV treated with endoscopic histoacryl injection at the Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, were included in the retrospective analysis. There were 45 patients in the group of splenectomy combined with pericardial devascularization (splenectomy group for short) and 80 patients in the non-splenectomy group. The efficacy of endoscopic treatment, postoperative variceal improvement, rebleeding rate, and complications were analyzed between the two groups.Results:Endoscopic histoacryl injection was successfully completed in all 125 patients, and the median volume of histoacryl was 4.5 mL. The overall effective rate in splenectomy and non-splenectomy group was 80.0% (36/45) and 57.5% (46/80), respectively. The difference in the number of significantly effective, effective, and ineffective cases between the two groups was statistically significant (16, 20, 9 cases, and 20, 26, 34 cases, respectively, χ 2=6.469, P=0.039). Two and 14 patients developed rebleeding in the splenectomy group and non-splenectomy group, respectively; and the difference in the rebleeding rate between the two groups was statistically significant (4.4% VS 17.5%, Log-rank P=0.039). No patient died within 1 year in either group, and no serious complications such as ectopic embolism occurred. Conclusion:After splenectomy combined with pericardial devascularization in cirrhotic patients with EGV and hypersplenism, the application of histoacryl has better short-term efficacy and can significantly reduce the rebleeding rate compared with the non-splenectomy group.

OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively. RESULTS: 4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine. CONCLUSION The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.
Humans ; Dendritic Cells ; Retrospective Studies ; Skin Neoplasms/pathology* ; Antineoplastic Agents/therapeutic use* ; Bone Marrow/pathology* ; Myeloproliferative Disorders ; Hematologic Neoplasms/drug therapy*

Humans ; Otosclerosis/surgery* ; Stapes ; Stapes Surgery/adverse effects* ; Arteries