Objective To observe the clinical efficacy of Qigui Tongluo Oral Liquid(a hospital preparation developed by Guangdong Second Traditional Chinese Medicine Hospital and being composed of Astragali Radix,Angelicae Sinensis Radix,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Achyranthis Bidentatae Radix,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Pheretima,etc.)combined with moxibustion for the treatment of chronic fatigue syndrome(CFS)of qi deficiency and blood stasis type on the basis of qi-collateral theory.Methods A retrospective study was conducted in 60 CFS patients with qi deficiency and blood stasis type.The patients were divided into an observation group and a control group,with 30 patients in each group according to the therapy.The control group was treated with mild moxibustion on Shenque(CV8)point with moxa sticks,and the observation group was treated with Qigui Tongluo Oral Liquid on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Fatigue Scale-14(FS-14)scores,serum immunoglobulin IgA,IgM,IgG levels,and cortisol(COR)level in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 96.67%(29/30),and that of the control group was 80.00%(24/30).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores and FS-14 scores of patients in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the effect on decreasing TCM syndrome scores and FS-14 scores in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum IgA and IgG levels of the two groups as well as the serum IgM and COR levels of the observation group were significantly increased compared with those before treatment(P＜0.01),and the effect of the observation group on increasing serum IgA,IgM,IgG,and COR levels was significantly superior to that of the control group(P＜0.05 or P＜0.01).(4)During the treatment,there were no significant adverse reactions occurring in the two groups.Conclusion Healthy-qi deficiency and collateral obstruction contribute to the core pathogenesis of CFS.Based on the TCM qi-collateral theory and following the therapeutic principle of replenishing deficiency and unblocking collaterals,Qigui Tongluo Oral Liquid combined with moxibustion for the treatment of CFS patients with qi deficiency and blood stasis type can achieve certain efficacy.The combined therapy could significantly alleviate the clinical symptoms,improve the immunity level,and regulate the neuro-endocrine-immune(NEI)network of the patients.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

ObjectiveTo investigate the value of percutaneous and intravenous contrast-enhanced ultrasound（P-Ⅳ-CEUS） in sentinel lymph nodes（SLNs） after resection of early-stage primary breast cancer. MethodsA retrospective analysis was done on the clinical and imaging data of 42 early breast cancer patients. Following primary tumor resection， all these patients underwent reoperation in our hospital. SLNs were examined by preoperative P-Ⅳ-CEUS and intraoperative sentinel lymph node biopsy（SLNB） was performed by using Methylene blue as a tracer. Then we analyzed the detection and false-negative rate in CEUS and SLNB respectively. By using the surgical pathological results as the gold standard， the diagnostic efficacy of CEUS for SLNs was explored. ResultsThe detection rate and false negative rate of SLNs in percutaneous contrast-enhanced ultrasound （P-CEUS） were 92.9% （39/42） and 7.1% （3/42）， respectively. The detection rate in methylene blue staining was 100% （41/41） and one patient underwent neoadjuvant therapy due to biopsy-confirmed metastasis. The sensitivity， specificity， positive predictive value， negative predictive value and accuracy of P-Ⅳ-CEUS were 66.7% （2/3）， 100% （37/37）， 100% （2/2）， 97.3% （36/37） and 97.4% （38/39）， respectively. ConclusionsP-Ⅳ-CEUS after resection of early-stage primary breast cancer can accurately detect SLNs and characterize their status， which is a reliable clinical basis for reducing invasive SLNB.

Abstract: Objective　To investigate the fundus arteriosclerosis and its influencing factors in HIV/AIDS patients after long-term highly active antiretroviral therapy (HAART). Methods　The clinical basic data and fundus examination data of 203 HIV/AIDS patients before and after HAART in the Fourth People 's Hospital of Nanning from January 2020 to June 2022 were collected to evaluate the occurrence of fundus arteriosclerosis and analyze its influencing factors. Results　Of the 203 HIV/AIDS patients, 159 patients developed fundus arteriosclerosis, with an incidence of 78.33%, including 33 patients with grade Ⅰ(20.75%), 87 patients with grade Ⅱ (54.72%), 28 patients with grade Ⅲ(17.61%), and 11 patients (6.92%) with Grade Ⅳ. Before HAART, there was no significant difference in CD4+T lymphocyte count, CD8+T lymphocyte count, viral load, white blood cell count, platelet count, hemoglobin, serum creatinine, blood urea nitrogen, triacylglycerol, total cholesterol, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase and serum total bilirubin between the atherosclerosis group and normal group (P>0.05). After 6 months of HAART, CD8+T lymphocyte count, triacylglycerol and fasting blood glucose in atherosclerosis group were significantly higher than those in normal group (P<0.05). In the stratified comparison of CD4+ and CD8+ lymphocyte counts after 6 months of HAART, the proportion of patients with CD4+ lymphocyte count (CD4+)<200 (cells/μL) in the atherosclerosis group was significantly higher than that in the normal group; the proportion of patients with CD4+ lymphocyte count (CD4+)≥500 (cells/μL) was significantly lower than that in the normal group; the proportion of patients with CD8+ lymphocyte count CD8+≥ 800/μL was significantly higher than that in the normal group (all P<0.05). Binary logistic regression analysis showed that opportunistic infection, HIV course, CD4+T, CD8+T lymphocyte count after HAART and triglyceride were independent risk factors for ocular fundus atherosclerosis in HIV/AIDS patients (all P<0.05). Conclusions　The incidence of ocular fundus arteriosclerosis is high in HIV/AIDS patients. More than 4 years of HIV course, combined opportunistic infection, Low CD4+T lymphocyte count after 6 months of HAART, high CD8+T lymphocyte count and high triglyceride level are independent risk factors for ocular fundus arteriosclerosis in HIV/AIDS patients. Fundus screening should be performed before and after HAART in such population, HAART program should be formulated for the risk of cardiovascular disease, and risk management of cardiovascular disease should be strengthened during treatment to improve patient outcomes.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.
Humans ; Male ; Female ; Aged ; Adult ; Middle Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/pathology* ; B7-H1 Antigen/metabolism* ; Lung Neoplasms/pathology* ; Retrospective Studies ; China ; Prognosis ; Biomarkers, Tumor/analysis* ; DNA Helicases/genetics* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

There is a rare case of an elderly diabetic with diabetic foot infection at Hainan General Hospital in September 2021, which was diagnosed as Corynebacterium diphtheriae infection incidentally on routine culture with conventional methods and molecular biological approaches, to aid in diagnosis in clinical practice. Owing to smear staining, Albert staining and VITEK 2 system, automated identification systems viz matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) confirmed combing with 16S ribosomal RNA (16S rRNA) gene has been used for the taxonomic classification of bacteria. Otherwise, toxin gene tox was done for diphtheria toxin synthesis. The isolate was Gram-stain-positive, rod-like arrangement with irregular thickness, with characteristic metachromatic granules, ferment most sugars and homology of 16S rRNA analyses with C. diphtheriae NCTC11397^T (MW682323.1) was greater than a 100% possibility, toxin gene tox was negative. The findings lay the foundation to clinical identify and trace of non-toxigenic C. diphtheriae. Moreover, this work provides insights into the non-toxigenic C.diphtheriae that contribute to recognized risk of non-toxigenic C.diphtheriae infections.
Aged ; Corynebacterium/genetics* ; Corynebacterium diphtheriae/genetics* ; Diabetes Mellitus ; Diabetic Foot ; Diphtheria/microbiology* ; Humans ; RNA, Ribosomal, 16S/genetics*