The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

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 the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Apoptosis ; Benzothiazoles ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Paclitaxel/therapeutic use* ; Phenylurea Compounds ; RNA, Messenger ; STAT5 Transcription Factor/pharmacology* ; Signal Transduction ; fms-Like Tyrosine Kinase 3

Alzheimer's disease (AD), also known as dementia , is a progressive neurodegenerative disease. The main clinical manifestations of AD patients are memory loss, cognitive dysfunction, abnormal behavior and social impairment . At present , there is no effective treatment available for AD, so early prevention and control is particularly important. Since ancient times, the theory of ^“medicine and food are of the same origin^” has existed in traditional Chinese medicine, therefore, a variety of food supplements have been used in the intervention and control of the progress of various diseases. Reasonable diet plays an important role in the early prevention and control of AD. This paper mainly reviews the effects of common plant polyphenols, vitamins, and fatty acids on the pathogenesis of AD, in order to clarify the role of dietary nutrients in the early prevention and control of AD, and to provide theoretical support for adjusting the dietary structure to improve brain health.

OBJECTIVE: To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology. METHODS: The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting. RESULTS: Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05). CONCLUSION Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Myocardial Infarction/drug therapy* ; Network Pharmacology

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in β-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aβ secretion, which was caused by down-regulation of β-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aβ secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.
Alzheimer Disease ; Amyloid Precursor Protein Secretases/metabolism* ; Amyloid beta-Peptides/metabolism* ; Aspartic Acid Endopeptidases/metabolism* ; Down-Regulation ; Forkhead Box Protein O1/genetics* ; Humans ; Phosphorylation ; STAT3 Transcription Factor/metabolism* ; Secosteroids

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

OBJECTIVETo investigate clinical efficacy and experience of total knee arthroplasty in treating knee osteoarthritis patients with Parkinson's disease.

METHODSFrom January 2011 to January 2014, 19 knee osteoarthritis patients with Parkinson's disease treated with total knee arthroplasty were collected. Among them, including 9 males and 10 females aged from 61 to 83 years old with an average of 71.3 years old. Radiology results were checked before and after operation. VAS score and KSS score were applied to evaluate clinical effects. Patients were classified according to HoehnYahr grade, 3 cases in grade 1, 4 cases in grade 1.5, 2 cases in grade 2, 4 cases in grade 2.5, 2 cases in grade 3 and 1 case in grade 4.

RESULTSNineteen patients were followed up from 3 to 7 years with an average of 4.3 years. The pain of patients was significantly reduced or disappeared. All incisions were healed at stage I. At the latest follow-up, 3 patients had knee pain, and mild pain in 1 patient, moderate in 1 patient without severe pain. VAS score was reduced from preoperative 8.4±1.3 to the latest follow-up 3.1±1.2, the difference was statistically significant (0.05). KSS score improved from 43.6±7.3 before operation to 91.8±10.6 after operation. The condition of Parkinson's were controlled by medicine. No loosening and subsidence of prosthesis by X-ray examination.

CONCLUSIONSTotal knee arthroplasty is a safe and effective method for the treatment of Parkinson's disease and has satisfactory mid-term clinical effect.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Knee ; Female ; Follow-Up Studies ; Humans ; Knee Joint ; Knee Prosthesis ; Male ; Middle Aged ; Osteoarthritis, Knee ; surgery ; Parkinson Disease ; complications ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore clinical efficacy of hip replacement for hip-joint diseases with Parkinson disease.

METHODSFrom December 2011 to December 2016, 18 patients with hip-joint diseases with Parkinson disease treated by hip replacement, including 8 males and 10 females aged from 59 to 87 years old with an average of 71 years old. Among them, 3 cases were developmental dysplasia of hip, 3 cases were femoral head necrosis and 12 cases were femoral neck fracture. All patients manifested with obvious pain and limitation of stepping ability. Postoperative complications were observed and Harris score were used to compare hip joint function after operation.

RESULTSThe incision were healed well, and pain were alleviated or disappeared, and hip joint function were improved. Eighteen patients were followed up from 1 to 3 years with an average of 2.3 years. At the latest follow up, 14 cases recovered freedom-walk, 2 cases could walk with walking stick, 1 case could walk with walking aid and 1 case was died. Among 18 patients, 2 cases were occurred dislocation, and 1 case were died for cardiac disease at 3 months after operation. Four patients were occurred slight pain. There were significant differences in Harris scores among preoperative (41.7±1.4), 6 months after operation(80.1±5.4) and the final follow-up (83.4±2.1), and 10 cases got excellent result, 4 good, 1 fair and 2 poor.

CONCLUSIONSApplication of hip replacement for hip-joint diseases with Parkinson disease is a safe and effective clinical therapy, and has advantages of less complications and rapid recovery of hip joint function.

BACKGROUNDThe risk of radial artery occlusion (RAO) needs particular attention in transradial intervention (TRI). Therefore, reducing vascular occlusion has an important clinical significance. The aim of this study was to determine the appropriate puncture site during TRI through comparing the occurrence of RAO between the different puncture sites to reduce the occurrence of RAO after TRI.

METHODSWe prospectively assessed the occurrence of RAO in 606 consecutive patients undergoing TRI. Artery occlusion was evaluated with Doppler ultrasound in 2 days and 1 year after the intervention. Risk factors for RAO were evaluated using a multivariate model analysis.

RESULTSOf the 606 patients, the RAO occurred in 56 patients. Compared with TRI at 2-5 cm away from the radius styloid process, the odds ratio (OR) for occlusion risk at 0 cm and 1 cm were 9.65 (P = 0.033) and 8.90 (P = 0.040), respectively. The RAO occurred in the ratio of the arterial diameter to the sheath diameter ≤1 (OR = 2.45, P = 0.004).

CONCLUSIONDistal puncture sites (0-1 cm away from the radius styloid process) can lead to a higher rate of RAO.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/NCT01979627?term = NCT01979627 and rank = 1.

Aged ; Arterial Occlusive Diseases ; etiology ; Cardiac Catheterization ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Punctures ; Radial Artery