Objective To explore the characteristics of traditional Chinese medicine(TCM)syndrome,syndrome elements and their combination,and the distribution of TCM syndrome types in advanced non-small cell lung cancer(NSCLC)patients suffering from hypothyroidism after treatment with immune checkpoint inhibitors(ICIs).Methods The analysis was conducted on 168 patients with NSCLC at stage ⅢB-ⅣB confirmed by pathological findings,whose epidermal growth factor receptor/anaplastic lymphoma kinase(EGFR/ALK)was negative,and then suffering from hypothyroidism after treatment with ICIs from January 2020 to June 2023,who admitted to Zhongshan Hospital of Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine.The patients'information collected by four diagnostic methods of TCM was analyzed,and then cluster analysis was used to explore the characteristics of TCM syndrome and the distribution of TCM syndrome types of immunotherapy-induced hypothyroidism in advanced NSCLC.Moreover,the distribution of TCM syndrome types in the patients with different genders,age groups,and hypothyroidism grades was analyzed.Results(1)The TCM syndrome of hypothyroidism appearing in 168 patients with advanced NSCLC after immunotherapy was characterized by deficiency type,which manifested as follows:cough,fatigue and weakness,amnesia,lusterless complexion,spontaneous sweating,dry skin,white sputum,unwilling to talk,dizziness,nocturnal polyuria,blurred vision,emaciation,poor skin elasticity,poor appetite or even anorexia,somnolence,long-term poor appetite,edema,insomnia,low voice,dull pain,light white color of fingernails,spitting,frequently intolerance of cold,thirst,bright pale complexion,preference of warmth and aversion to cold,thirst with preference of hot drink,dyspnea,frequent constipation,dry stools,puffiness of face and eyelid,dreaminess,abdominal fullness,lumbar pain,and weakness in defecation.The tongue manifestation and pulse condition were characterized by white and thin coating,pale-red tongue,tongue with tooth-marks,pale and enlarged tongue,pale tongue,deep pulse,slippery pulse,feeble pulse,weak cubital pulse,and thready pulse.(2)The disease-location syndrome elements usually involved in the lung,spleen,and kidney,and the disease-nature syndrome elements usually involved in qi deficiency,yang deficiency,blood deficiency,and water retention.(3)The cluster analysis yielded three syndrome types,and they were lung and spleen qi deficiency syndrome,kidney yang deficiency syndrome,and qi deficiency and water retention syndrome in decreasing sequence of occurrence frequency.(4)Statistically significant difference of the distribution of TCM syndrome types was presented in the patients with various age groups(P<0.01).Lung and spleen qi deficiency syndrome was the main syndrome type in the patients aged 60-69 years old,kidney yang deficiency syndrome was frequently seen in the patients being or over 70 years old,and qi deficiency and water retention syndrome was frequently seen in the patients less than 50 years old.No statistically significant difference of the distribution of TCM syndrome types was presented in the patients with various genders and in the patients with various grades of hypothyroidism(P>0.05).Conclusion The immunotherapy-induced hypothyroidism in patients with advanced NSCLC is usually differentiated as the TCM syndrome types of lung-qi and spleen-qi deficiency,kidney yang deficiency,and qi deficiency and water retention.Deficiency of healthy qi contributes to the fundamental pathogenesis of the development and progression of the disease.Clinicians should pay attention to the changes of symptoms in time and monitor the thyroid function indicators of the patients,thus to avoid serious immunotherapy-related adverse events(irAEs).

Objective The causal relationship between endometriosis(EMs)and 15 trace elements including copper,calcium,carotene,folic acid,iron,magnesium,potassium,selenium,vitamin A,vitamin B12,vitamin B6,vitamin C,vitamin D,vitamin E and zinc was analyzed by double sample Mendelian randomization(MR).Methods Multiple trace elements were used as exposure factors,and the incidence risk of EMs was used as the outcome factor for two-sample MR analysis.The data were sourced from the publicly available integrative epidemiology unit open Genome-Wide Association Studies database and Finnish Genome Research Project database.Five Mendelian randomization analysis methods were employed to investigate the causal relationship between EMs and trace elements.Additionally,sensitivity analysis was carried out to evaluate the influence of heterogeneity and horizontal pleiotropy on the results of the MR analysis.Results The impact of trace elements on various types of EMs varies.The results of the inverse variance weighted(IVW)method indicated that trace element calcium(OR=1.465,95％CI:1.094-1.962)and vitamin B6(OR=1.580,95％CI:1.146-2.178)might be risk factors for ovarian EMs.Vitamin B6(OR=0.203,95％CI:0.044-0.939)may be a protective factor for tubal EMs.The above research results were not affected by heterogeneity and horizontal pleiotropy(P＞0.05).This study did not find a causal relationship between other trace elements and EMs.Conclusion The trace elements calcium and vitamin B6 predicted by genetics may play a regulatory role in the development of EMs.

BACKGROUND:The induced membrane technique(Masquelet technique)is a novel two-stage surgical approach for the reconstruction of large bone defects,gaining increasing popularity in clinical applications.However,the precise mechanism underlying its bone defect repair is still not fully understood.OBJECTIVE:To review the background,repair mechanism and advantages of the induced membrane technique,the characteristics of the induced membrane,membrane-bone graft communication,selection of animal models,types and morphology of bone cement,the effects of loaded antibiotics on the induced membrane,choice of fixation methods,and bone tissue engineering materials to provide new insights for the future treatment of critical-sized bone defects and the improvement of the induced membrane technique.METHODS:A literature search was conducted in PubMed,Web of Science,and CNKI databases,covering publications from 1986 to 2024.A total of 890 references were retrieved.Manual screening and analysis were performed based on inclusion criteria related to the fundamental research of induced membrane technique,excluding those with poor relevance to the topic and duplicates.The included literature comprised original experimental studies,reviews,meta-analyses and other relevant publications.Finally,72 articles were included for summary and analysis.RESULTS AND CONCLUSION:(1)The mechanism underlying the bone defect repair using this technique remains unclear,but both the membrane and bone grafting are indispensable.(2)The induced membrane is a distinctively layered tissue rich in various bone-forming related cells,growth factors,and blood vessels,with its vascularization and secretion of growth factors dynamically changing overtime.(3)In terms of animal model selection,sheep are more similar to humans in anatomical structure,weight-bearing patterns,and bone remodeling.However,rats are more suitable considering their lower feeding costs,easier handling,and shorter modeling period.(4)Polymethyl methacrylate is not the only material that can be used to induce a biomembrane,and there may be more suitable materials capable of inducing higher-quality biomembranes.The recommended dose of antibiotics(primarily vancomycin)is 1-4 g per 40 g polymethyl methacrylate.(5)For animal fixation,especially in rats,the use of steel plates is more widespread,providing a more reliable and reproducible fixation method.(6)In the future,there is potential for new materials to replace autogenous bone and enhance the bone repair capabilities of the Masquelet technique.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

Objective The causal relationship between endometriosis(EMs)and 15 trace elements including copper,calcium,carotene,folic acid,iron,magnesium,potassium,selenium,vitamin A,vitamin B12,vitamin B6,vitamin C,vitamin D,vitamin E and zinc was analyzed by double sample Mendelian randomization(MR).Methods Multiple trace elements were used as exposure factors,and the incidence risk of EMs was used as the outcome factor for two-sample MR analysis.The data were sourced from the publicly available integrative epidemiology unit open Genome-Wide Association Studies database and Finnish Genome Research Project database.Five Mendelian randomization analysis methods were employed to investigate the causal relationship between EMs and trace elements.Additionally,sensitivity analysis was carried out to evaluate the influence of heterogeneity and horizontal pleiotropy on the results of the MR analysis.Results The impact of trace elements on various types of EMs varies.The results of the inverse variance weighted(IVW)method indicated that trace element calcium(OR=1.465,95％CI:1.094-1.962)and vitamin B6(OR=1.580,95％CI:1.146-2.178)might be risk factors for ovarian EMs.Vitamin B6(OR=0.203,95％CI:0.044-0.939)may be a protective factor for tubal EMs.The above research results were not affected by heterogeneity and horizontal pleiotropy(P＞0.05).This study did not find a causal relationship between other trace elements and EMs.Conclusion The trace elements calcium and vitamin B6 predicted by genetics may play a regulatory role in the development of EMs.

BACKGROUND:The induced membrane technique(Masquelet technique)is a novel two-stage surgical approach for the reconstruction of large bone defects,gaining increasing popularity in clinical applications.However,the precise mechanism underlying its bone defect repair is still not fully understood.OBJECTIVE:To review the background,repair mechanism and advantages of the induced membrane technique,the characteristics of the induced membrane,membrane-bone graft communication,selection of animal models,types and morphology of bone cement,the effects of loaded antibiotics on the induced membrane,choice of fixation methods,and bone tissue engineering materials to provide new insights for the future treatment of critical-sized bone defects and the improvement of the induced membrane technique.METHODS:A literature search was conducted in PubMed,Web of Science,and CNKI databases,covering publications from 1986 to 2024.A total of 890 references were retrieved.Manual screening and analysis were performed based on inclusion criteria related to the fundamental research of induced membrane technique,excluding those with poor relevance to the topic and duplicates.The included literature comprised original experimental studies,reviews,meta-analyses and other relevant publications.Finally,72 articles were included for summary and analysis.RESULTS AND CONCLUSION:(1)The mechanism underlying the bone defect repair using this technique remains unclear,but both the membrane and bone grafting are indispensable.(2)The induced membrane is a distinctively layered tissue rich in various bone-forming related cells,growth factors,and blood vessels,with its vascularization and secretion of growth factors dynamically changing overtime.(3)In terms of animal model selection,sheep are more similar to humans in anatomical structure,weight-bearing patterns,and bone remodeling.However,rats are more suitable considering their lower feeding costs,easier handling,and shorter modeling period.(4)Polymethyl methacrylate is not the only material that can be used to induce a biomembrane,and there may be more suitable materials capable of inducing higher-quality biomembranes.The recommended dose of antibiotics(primarily vancomycin)is 1-4 g per 40 g polymethyl methacrylate.(5)For animal fixation,especially in rats,the use of steel plates is more widespread,providing a more reliable and reproducible fixation method.(6)In the future,there is potential for new materials to replace autogenous bone and enhance the bone repair capabilities of the Masquelet technique.

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the risk factors for intraoperative hemorrhage during endoscopic submucosal dissection (ESD) for colorectal lesions.Methods:Data of 386 patients with colorectal lesions, who underwent ESD at The Third People's Hospital of Datong and its cooperative hospital, Nanjing Drum Tower Hospital, from December 2019 to August 2021 were retrospectively analyzed. The patients were divided into the hemorrhage group ( n=85) and the non-hemorrhage group ( n=301) according to intraoperative hemorrhage. The correlationship of patients'basic information, lesion-related factors and hemorrhage during colorectal ESD was analyzed. Univariate and multivariate logistic regression were used to identify the risk factors for intraoperative hemorrhage during ESD. The risk predictive model of intraoperative hemorrhage during ESD was established according to the screened risk factors, and receiver operator characteristic (ROC) curve was used to evaluate the predictive model. Results:Univariate logistic regression showed that a history of diabetes ( OR=2.340, P<0.05), a history of coronary atherosclerotic heart diseases ( OR=3.100, P<0.05), the lesion located in the rectum ( OR=3.272, P<0.05), longer lesion ( OR=1.093, P<0.05), wider lesion ( OR=1.057, P<0.05), larger lesion ( OR=1.126, P<0.05), depressed lesion ( OR=6.128, P<0.05), the laterally spreading lesion ( OR=2.651, P<0.05), the lesion infiltrated into the SM-S layer ( OR=0.088, P<0.05), the lesion infiltrated into the SM-D layer ( OR=0.174, P<0.05), the diameter of hemorrhage vessels 0.5~<1.0 times of the diameter of incision knife ( OR=246.854, P<0.05), the postoperative pathology as early cancer ( OR=7.000, P<0.05) were risk factors for intraoperative hemorrhage during ESD. Considering the quantitative relationship between the length, the width and the area of lesions, multi-factor models were constructed using the length and area of lesions respectively. Forward stepwise regression was used to screen variables and determine the final model, and the results showed that a history of coronary atherosclerotic heart diseases, the depressed lesion, the longer lesion, the larger lesion, the diameter of hemorrhage vessels 0.5~<1.0 times of the diameter of the incision knife were independent risk factors for intraoperative hemorrhage during ESD. The two modeling results of the lesion length and the lesion area were very similar. Therefore, lesion length was recommended to describe lesions in clinical practice. Conclusion:A history of coronary atherosclerotic heart disease, the depressed lesion, the longer lesion, the larger lesion, the diameter of vessels 0.5~<1.0 times of that of the incision knife are independent risk factors for intraoperative hemorrhage during ESD.

Objective:To investigate the independent predictors of colorectal polyps complicating colorectal laterally spreading tumors (CLST) and the independent risk factors for malignancy in CLST coexisting with colorectal polyps.Methods:Clinical data of 260 patients with CLST who underwent endoscopy and received treatment in the Second Affiliated Hospital of Dalian Medical University from January 2016 to December 2021 were retrospectively collected. Patients were divided into the coexisting group ( n=135) and the non-coexisting group ( n=125) according to the presence or absence of polyps. Differences in clinicopathological characteristics between the two groups were compared and binary logistic regression was used to analyse the predictors of coexistence. Then the coexisting group was further divided into coexisting malignant group ( n=38) and coexisting non-malignant group ( n=97) according to the infiltration depth of CLST, and binary logistic regression was used to analyse the risk factors for malignancy in CLST coexisting with colorectal polyps. Results:Male ( P=0.002, OR=2.355, 95% CI:1.354-4.099), villous tubular adenoma ( P=0.022, OR=3.873, 95% CI: 1.214-12.355) and polyps history ( P=0.001, OR=2.738, 95% CI: 1.527-4.909) were independent predictors for colorectal polyps coexisting with CLST. Area under the curve (AUC) of the predictive model was 0.725 ( P<0.001, 95% CI: 0.664-0.786). Polyp diameter≥10 mm ( P=0.007, OR=6.266, 95% CI:1.634-24.034), CLST diameter≥20 mm ( P<0.001, OR=11.879, 95% CI:4.078-34.601), granular-mixed type CLST ( P=0.003, OR=8.584, 95% CI: 2.126-34.660), flat-elevated type CLST ( P=0.021, OR=4.399, 95% CI: 1.250-15.482) and pseudo-depressed type CLST ( P<0.001, OR=31.426, 95% CI: 4.975-198.509) were independent risk factors for malignancy in CLST coexisting with polyps. AUC of the predictive model was 0.854 ( P<0.001, 95% CI: 0.775-0.933). Conclusion:Male CLST patients with polyps history and a pathological type of villous tubular adenoma are more likely to develop coexistence. In patients with CLST which is granular-mixed type, flat-elevated type and pseudo-depressed type coexisting with colorectal polyps, the larger the diameter of the polyp and the diameter of the CLST, the more likely it is to be malignant.