In the study, to explore the anti-tumor effects and mechanisms of chlorpromazine (CPZ) and perphenazine (PPZ) combined with temozolomide (TMZ) on human glioma cell lines, we performed MTT assays to determine the growth inhibitory rate of CPZ, PPZ and TMZ in mono and combined treatments. The anti-tumor effects of CPZ and PPZ alone or in combination with TMZ were determined by colony formation, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) detection (JC-1). The expression level of p53 was detected by immunofluorescence assay. Furthermore, autophagy under different administrations was detected by flow cytometry and confocal imaging to explore the anti-tumor mechanism of CPZ and TMZ. Protein phosphatase 2A (PP2A), cancerous inhibitor of protein phosphatase 2A (CIP2A) and proto-oncogene protein (c-Myc) were detected by immunofluorescence assay, tumor stem cell markers (CD44, CD133) and aldehyde dehydrogenase (ALDH) were detected by flow cytometry to explore the anti-tumor mechanism of PPZ and TMZ. The results showed that after 72 h treatments of combinations, the values of half maximal inhibitory concentration (IC₅₀) of TMZ on U87 and U251 cells were reduced, and the ability of TMZ to induce apoptosis and cycle arrest was improved. In addition, the combination of CPZ and TMZ could induce an increased effect of autophagy via activating the relevant pathway of p53 gene in glioma cells. The combination of PPZ and TMZ increased the sensitivity of glioma cells to TMZ, and the underlying mechanism might be related to the inhibition of CIP2A/PP2A/c-Myc signaling pathway. In conclusion, CPZ and PPZ combined with TMZ, showed the significant synergistic effects in cancer treatment, which are the novel and potential therapeutic regimens providing a new treatment strategy for human glioma.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was mean_CIMT=0.324 7+0.006 9×age and SD_CIMT=0.076 9+0.001 2×age. For women, the regression was mean_CIMT=0.354 9+0.005 4×age and SD_CIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male ; Humans ; Adult ; Female ; Carotid Intima-Media Thickness ; Cardiovascular Diseases ; Reference Values ; Carotid Arteries/diagnostic imaging* ; Ultrasonography, Carotid Arteries ; Risk Factors ; Carotid Artery Diseases

Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans ; Acupuncture Therapy ; Periosteum ; Analgesia ; Pain Management ; Consciousness ; Pain

Background: The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values. Methods: In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Results: The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P<0.05). TSH, total thyroxine (TT4), and ATPO levels were significantly correlated with age (P<0.05). The serum levels of TSH, ATG, and ATPO in men were significantly lower than in women; in contrast, the serum TT3 level was significantly higher in men than in women (P<0.05). Serum TSH, TT3, TT4, and ATG levels differed across age groups (P<0.05), but no such variation was observed for ATG levels (P>0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values. Conclusion The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer’s manual. Validated sex-specific values are required for diagnosing thyroid diseases.

Humans ; White Matter/pathology* ; Central Nervous System Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.
Adult ; Adolescent ; Humans ; Prognosis ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Hematopoietic Stem Cell Transplantation ; Lymphoma, T-Cell ; Unrelated Donors