The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVES: This study aimed to evaluate the application value of a modified retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle in the resection of benign parotid gland tumors. METHODS: Forty-eight patients with benign parotid gland tumors were retrospectively analyzed: 19 cases were included in the experimental group with an improved retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle, and 29 cases were assigned in the control group with a modified facelift incision. Operation time, postoperative drainage, postoperative esthetic degree, and incidence of facial nerve paralysis, salivary fistula, and Frey's syndrome were compared. RESULTS: After the esthetic procedure, the average score of the experimental group was higher than that of the control group, and the esthetic effect of the former was better than that of the latter ( CONCLUSIONS The modified retroauricular hairline incision and sternocleidomastoid flap with an inferior pedicle can be applied to resect benign parotid gland tumors safely. It shows a better cosmetic effect and does not cause obvious postoperative complications. Therefore, it should be promoted for tumor treatments.
Esthetics, Dental ; Humans ; Parotid Gland/surgery* ; Parotid Neoplasms/surgery* ; Postoperative Complications ; Retrospective Studies ; Sweating, Gustatory

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

Objective To compare laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy for the treatment of obese patients with type 2 diabetes mellitus.Methods A retrospective analysis of T2DM patients with LRYGB (28 cases) and LSG (35 cases) was enrolled from Jan 2010 to Jun 2013.Results The indicator such as BMI,fasting glucose,fasting insulin,HbA1c,and insulin resistance were significantly lower in 1 year,3 years and 5 years after operation [LRYGB group:(37.3 ±3.7) kg/m2 to (32.3 ± 3.4) kg/m2 to (28.8 ± 3.0) kg/m2 to (25.5 ± 2.8) kg/m2,t =13.670,15.499,21.710,P=0.000,0.000,0.000;(8.2 ± 1.8) mmol/L to (6.0 ± 1.3) mmol/L to (5.2 ±0.9) mmol/L to (4.7±0.5) mmol/L,t =6.664,8.723,10.282,P=0.000,0.000,0.000;(32.2±17.0) μ IU/ml to (16.1 ± 12.1) μIU/ml to (8.6 ±5.2) μ IU/ml to (5.2 ±2.8) μIU/ml,t =7.453,8.218,8.687,P =0.000,0.000,0.000;(7.4％ ±0.6％) to (6.2％ ±0.7％) to (5.7％ ±0.7％) to (5.1％ ±0.6％),t =11.362,18.771,21.186,P=0.000,0.000,0.000;(12.0±7.3) to (4.6±4.3) to (2.1 ±1.7) to (1.1 ±0.7),t =6.455,7.667,8.050,P=0.000,0.000,0.000;LSG group:(39.2±5.2) kg/m2 to (34.1 ±4.5) kg/m2to (29.3±4.0) kg/m2to (25.1 ±2.3) kg/m2,t=11.676,13.680,19.161,P=0.000,0.000,0.000;(8.0±2.9) mmol/L to (5.8±1.5) mmol/L to (5.1 ±0.9) mmol/L to (4.6 ±0.5) mmoL/L,t=5.467,6.921,7.741,P=0.000,0.000,0.000;(29.1 ±25.2) μIU/ml to (16.4±10.6) μ IU/ml to (8.8±5.5) μ IU/ml to (5.5 ±2.0) μIU/ml,t =3.512,5.232,5.702,P=0.001,0.000,0.000;(7.7％ ±1.3％) to (6.3％ ±0.6％) to (5.8％ ±0.6％) to (5.2％ ±0.6％),t=8.001,10.106,11.922,P =0.000,0.000,0.000;(9.8 ±9.6) to (3.9 ±2.2) to (1.9 ±1.0) to (1.1 ± 0.4),t =3.733,4.972,5.404,P =0.001,0.000,0.000].There was no significant difference between the two groups in 1 year,3 year and 5 year post-operation (DM remission:71％ to 69％,89％ to 80％,93％ to 89％) (P ＞ 0.05).Conclusion LRYGB and LSG have the same long-term efficacy for T2DM patients.

OBJECTIVETo compare the angiogenesis behaviors of vascular endothelial growth factor (VEGF) and Chinese medicine Xuefu Zhuyu Decoction (, XZD) treatments.

METHODSHuman microvascular endothelial cells (HMEC-1) were treated with various concentrations of either XZD-containing serum (XZD-CS) or VEGF for 24, 48, and 72 h, respectively. Cell viability, proliferation, migration, adhesion, and in vitro tube formation assays were used to assess their angiogenic effects.

RESULTSVEGF promoted all cellular phases involved in angiogenesis including cell viability, proliferation, migration, adhesion, and tube formation (<0.05 or <0.01). Unlike the continuous promotion effects of VEGF at the above stages, XZD inhibited cell viability and proliferation (<0.05 or <0.01) and only promoted tube formation in the early phase of angiogenesis (<0.01).

CONCLUSIONSThese two medications promote different angiogenesis behaviors, which might be an important reason for their distinct therapeutic profile in clinical usage.

Cell Adhesion ; drug effects ; Cell Cycle ; drug effects ; Cell Line ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Humans ; Microvessels ; cytology ; Neovascularization, Physiologic ; drug effects ; Vascular Endothelial Growth Factor A ; pharmacology

Objective: To evaluate the predictive value of PARIS bleeding score on in-hospital bleeding of acute myocardial infarction (AMI) patients after drug-eluting stent (DES) implantation with dual-antiplatelet therapy (DAPT). Methods: There were 27 594 AMI patients enrolled in China acute myocardial infarction (CAMI) registry between 2013-01-01 to 2014-09-30 from 107 hospitals, and 14 625 of them had successful in-hospital DES implantation with DAPT were studied. Based on BARC (bleeding academic research consortium definition) criteria, the end point major bleeding (MB) events were defined by both BARC type 3, 5 and BARC type 2, 3, 5; the incidence of in-hospital bleeding, clinical features and predictive value of PARIS bleeding score according to different BARC type were evaluated. Results: Compared with non-MB patients, MB patients had the higher PARIS bleeding score, P<0.001. Based on PARIS score risk stratification, taking BARC type 3, 5 as endpoint, 77/14 625 (0.53%) patients had bleeding events, PARIS scores were different among high risk, mid risk and low risk patients, P<0.001; bleeding risk in mid risk patients was 2.38 times higher than low risk patients, P=0.006 and bleeding risk in high risk patients was 4.78 times higher than low risk patients, P<0.001.Taking BARC type 2,3,5 as endpoint,223(1.52%)patients had bleeding events,bleeding risk in mid risk patients was 1.64 times higher than low risk patients, P=0.002 and bleeding risk in high risk patients was 2.23 times higher than low risk patients, P=0.001. ROC analysis showed that PARIS score had predictive value on both BARC type 3, 5 and BARC type 2, 3, 5 bleeding, area under curve (AUC) of BARC type 3, 5 (AUC: 0.672) was higher than AUC of BARC type 2, 3, 5 (AUC:0.596) (z=2.079, P=0.038), which implied that PARIS score had better predictive value in severe bleeding events. Conclusion: PARIS bleeding score had predictive value on in-hospital bleeding in AMI patients after DES implantation with DAPT, it can also be used in bleeding risk stratification. PARIS bleeding score had better predictive value on severe bleeding.