ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

The operating room is the core settings of various surgical treatments, and exhibits distinct attributes and systemic complexities. Medical staff who work long term in operating rooms face multiple exposures to potential health hazards. Especially with the progress of electrosurgical technology and the frequent use of electrosurgical equipment, the possible health effects of the resulting electrosurgical smoke to those working in operating rooms have gradually attracted attention. This paper reviewed the composition, hazard, exposure risk monitoring, and protective measures of electrosurgical smoke, aiming to deepen the understandings of potential health risks of electrosurgical smoke, improve the self-protection awareness of medical staff, strengthen attention to electrosurgical smoke protection in all hospitals, and ensure the occupational safety of medical staff.

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.