Trends and Patterns of Antibiotic Prescriptions in Primary Care Institutions in Southwest China, 2017-2022.

Purpose: To explore the prescription patterns and usage trends of antibiotics within primary care institutions located in underdeveloped regions of China from 2017 to 2022. Methods: A retrospective analysis of antibiotic prescriptions was conducted from 25 primary care institutions in Guizhou Province during the period of 2017-2022. Antibiotic prescriptions were categorized into appropriate and inappropriate use. Appropriate use is further categorized into preferred medication, and antibiotics can be used or substituted. Inappropriate use is further categorized into unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics. Factors associated with inappropriate use were investigated using generalized estimation equations. Holt-Winters and SARIMA models were employed to predict the number of inappropriate antibiotic prescriptions as the alternative model. Results: A total of 941,924 prescriptions were included, revealing a decreasing trend in both the number and inappropriate rates of antibiotic prescriptions from 2017 to 2022. Diseases of the respiratory system (70.66%) was the most frequent target of antibiotic use, with acute upper respiratory infections of multiple and unspecified sites representing 52.04% of these cases. The most commonly used antibiotics were penicillins (64.44%). Among all prescriptions, inappropriate antibiotic prescriptions reached 66.19%. Physicians aged over 35, holding the title of associate chief physician and possessing more than 11 years of experience were more likely to prescribe antibiotics inappropriately. The phenomenon of inappropriate antibiotic use was commoner among children aged five or younger. By comparing model parameters, it was determined that the SARIMA model outperforms the Holt-Winters model in predicting the number of inappropriate antibiotic prescriptions among primary care institutions. Conclusion: The number and inappropriate rates of antibiotic prescriptions in southwest China exhibited a downward trend from 2017 to 2022, but inappropriate prescription remains a serious problem in primary care institutions. Therefore, future efforts should focus on strengthening physician education, training, and clinical practice. Additionally, physicians' awareness of common misconceptions about inappropriate antibiotic use must be improved, and the prescribing behavior of physicians who fulfill patients' expectations by prescribing antibiotics needs to be modified.

Chidamide Inhibits Aerobic Metabolism to Induce Pancreatic Cancer Cell Growth Arrest by Promoting Mcl-1 Degradation.

Pancreatic cancer is a fatal malignancy worldwide and urgently requires valid therapies. Previous research showed that the HDAC inhibitor chidamide is a promising anti-cancer agent in pancreatic cancer cell lines. In this study, we elucidate a probable underlying anti-cancer mechanism of chidamide involving the degradation of Mcl-1. Mcl-1 is frequently upregulated in human cancers, which has been demonstrated to participate in oxidative phosphorylation, in addition to its anti-apoptotic actions as a Bcl-2 family member. The pancreatic cancer cell lines BxPC-3 and PANC-1 were treated with chidamide, resulting in Mcl-1 degradation accompanied by induction of Mcl-1 ubiquitination. Treatment with MG132, a proteasome inhibitor reduced Mcl-1 degradation stimulated by chidamide. Chidamide decreased O2 consumption and ATP production to inhibit aerobic metabolism in both pancreatic cancer cell lines and primary cells, similar to knockdown of Mcl-1, while overexpression of Mcl-1 in pancreatic cancer cells could restore the aerobic metabolism inhibited by chidamide. Furthermore, chidamide treatment or Mcl-1 knockdown significantly induced cell growth arrest in pancreatic cancer cell lines and primary cells, and Mcl-1 overexpression could reduce this cell growth inhibition. In conclusion, our results suggest that chidamide promotes Mcl-1 degradation through the ubiquitin-proteasome pathway, suppressing the maintenance of mitochondrial aerobic respiration by Mcl-1, and resulting in inhibition of pancreatic cancer cell proliferation. Our work supports the claim that chidamide has therapeutic potential for pancreatic cancer treatment.

Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells.

Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either in combination with gemcitabine, or alone. The pancreatic cancer BxPC-3 and PANC-1 cell lines were treated with triptolide, which resulted in time- and dose-dependent growth arrest. When incorporated into a sequential schedule, triptolide synergistically increased gemcitabine-induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B-cell lymphoma 2 family proteins and loss of mitochondrial membrane potential. Furthermore, triptolide enhanced gemcitabine-induced S phase arrest and DNA double-strand breaks, possibly through checkpoint kinase 1 suppression. The results of the present study suggest that triptolide has therapeutic potential for the treatment of pancreatic cancer, particularly when administered in combination with gemcitabine.

Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

Progestagen-associated endometrial protein (PAEP) is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater) and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.