Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

In recent years, colonic manometry has been gradually introduced into clinical practice. It helps clinicians to gain a better understanding of the physiology and pathophysiology of colonic contractile activity in healthy adults and patients with colonic dysfunction. More and more patterns of colonic motility are being discovered with the help of colonic manometry. However, the clinical significance of these findings still needs to be further investigated. This review enhances our understanding of colonic motility and the current state of development and application of colonic manometry, as well as the limitations, future directions and potential of the technique in assessing the impact of treatment on colonic motility patterns, by analyzing and summarizing the literature related to colonic manometry.
Humans ; Adult ; Gastrointestinal Motility/physiology* ; Colon/physiology* ; Colonic Diseases ; Manometry/methods* ; Clinical Relevance ; Constipation

OBJECTIVE: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer. METHODS: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve. RESULTS: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration. CONCLUSION It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.
Humans ; Female ; Adult ; Middle Aged ; Adolescent ; Breast Neoplasms/epidemiology* ; Cardiovascular Diseases/etiology* ; Proportional Hazards Models ; Logistic Models ; China/epidemiology*

Objective:To observe the clinical effect of combined application of Compound Amino Acid Capsule(8-11)(CAAC8-11)and L-carnitine(LC)in the treatment of idiopathic asthenospermia(IAS),and to explore its possible therapeutic mech-anism.Methods:Based on the principle of double-blind and control,we selected 120 cases of IAS meeting the diagnostic criteria of asthenospermia in the WHO Manual for the Examination and Processing of Human Semen(5th Ed)and randomly divided them into three groups of an equal number:CAAC8-11+LC,LC control and blank control,the former given CAAC8-11 in addition to LC oral liquid,and the latter two given LC oral liquid and life intervention,respectively,all for 12 weeks.We collected semen samples from all the patients before and after treatment,and examined perm motility,the contents of neutral α-glucosidase(NAG)and reactive oxy-gen species(ROS),sperm DNA fragmentation index(DFI),and the expression of the Nrf2 protein.Results:Compared with the baseline,the total sperm motility was significantly improved in the IAS patients after treated with CAAC8-11+LC([27.50± 0.77]％vs[32.50±0.74]％,P＜0.05)or LC only([27.60±0.66]％vs[30.90±0.70]％,P＜0.05),dramatically higher in the CAAC8-11+LC than in the LC and blank control groups(P＜0.01).The content of NAG in the epididymis was re-markably increased after treatment in the CAAC8-11+LC than in the LC and blank control groups([23.90±0.56]vs[21.20± 0.49]and[16.80±0.42]mU,P＜0.05),so was the expression of Nrf2(P＜0.05),while the ROS level was markedly de-creased in the former than in the latter two groups([81.60±2.50]vs[88.50±2.50]and[88.70±2.40]μg/ml,P＜0.05).Conclusion:CAAC8-11+LC has a good clinical effect on asthenospermia,with no adverse reactions,which may be attributed to its ability to regulate the high expression of Nrf2,decrease the production of ROS and reduce the damage of oxidative stress to sperm motility.

OBJECTIVE: To evaluate the early and mid-term clinical results of medial parapatellar soft tissue overlapping suture in total knee arthroplasty for treatment of severe osteoarthritis combined with permanent patellar dislocation. METHODS: We retrospectively analyzed the data of 12 patients (12 knees) diagnosed with severe knee osteoarthritis combined with permanent patellar dislocation undergoing total knee arthroplasty with medial parapatellar soft tissue overlapping suture. Knee Society Score (KSS), University of California Los Angeles (UCLA) activity-level rating, Visual Analog Scale (VAS) pain score, and knee range of motion of the patients were assessed before and 2 years after the surgery. Anteroposterior and lateral radiographs of the knee joint, full-length standing radiographs of the lower limbs and patellar axial radiographs were evaluated. RESULTS: The mean Knee Society Score of the patients increased from 34.2±11.1 before surgery to 73.5±6.3 at two years after the surgery (P < 0.001). The UCLA activity-level rating increased from an average of 3.8 ± 0.8 before surgery to 5.8 ± 0.6 at two years postoperatively (P=0.003). The mean VAS pain score decreased from 42.8±6.0 before surgery to 20.1±3.7 (P < 0.001) and the range of motion of the knee joint increased from 74.6±8.9 degrees to 97.5±4.5 degrees at two years (P < 0.001). The radiographs showed no signs of subluxation or dislocation of the patella in all the patients. CONCLUSIONS Medial parapatellar soft tissue overlapping suture in total knee arthroplasty can achieve good early and mid-term clinical results for treatment of severe osteoarthritis combined with permanent patellar dislocation.
Arthroplasty, Replacement, Knee/methods* ; Humans ; Osteoarthritis, Knee/surgery* ; Patella/surgery* ; Retrospective Studies ; Sutures

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals ; Apoptosis ; Boron/toxicity* ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Trichloroacetic Acid/toxicity* ; Tumor Suppressor Protein p53/metabolism*