Objective To explore the factors associated with complete resolution of sentinel lymph node metastasis(pCR)after neoadjuvant chemotherapy in breast cancer and to establish a predictive model.Methods The medical records of 136 female patients with breast cancer who received neoadjuvant chemotherapy in the First Hospital of Lanzhou University from January 2022 to February 2024 were retrospectively analyzed.According to the 80/20 rule,the patients were randomly divided into a training set(108 cases)and a validation set(28 cases).Based on the pathological examination results of axillary lymph node dissection(ALND)after neoadjuvant chemotherapy in breast cancer patients,they were classified into the sentinel lymph node pCR group and non-pCR group.Multivariate logistic regression analysis was used to screen the independent risk factors of sentinel lymph nodes failing to reach pCR.Build a nomogram prediction model based on the screened risk factors.By drawing the receiver operating characteristic(ROC)curve calculation curve,the area under ROC curve,sensitivity and specificity are used to evaluate the discrimination of the model.Results Among the 108 breast cancer patients,46 cases achieved pCR in the sentinel lymph nodes,accounting for 42.59％(46 cases/108 cases).In addition,33 cases(30.56％)achieved pCR in the primary tumor lesion.The non-pCR group showed a higher proportion of stage Ⅲ clinical staging,lymph node short-axis reduction of less than 50％before and after treatment,tumor maximum diameter reduction of less than 50％before and after treatment,lymph node type Ⅲ classification,and blood flow grade Ⅲ compared to the pCR group(P＜0.05).Multivariate logistic regression analysis showed that Clinical staging(OR=3.593,95％CI:1.276-10.121),lymph node short-axis reduction of less than 50％before and after treatment(OR=4.272,95％CI:1.517-12.032),tumor maximum diameter reduction of less than 50％before and after treatment(OR=3.710,95％CI:1.317-10.449),lymph node type(OR=3.827,95％CI:1.359-10.779),and blood flow grade(OR=4.764,95％CI:1.691-13.418)were identified as risk factors for not achieving pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The sensitivity of the risk model for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in the training set of breast cancer patients was 0.826(95％CI:0.705-0.943),with a specificity of 0.826(95％CI:0.712-0.919)and an area under the ROC curve of 0.847(95％CI:0.738-0.952).In the validation set,the sensitivity for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients was 0.731(95％CI:0.608-0.904),with a specificity of 0.827(95％CI:0.713-0.941)and an area under the ROC curve of 0.834(95％CI:0.729-0.951).Conclusion Clinical staging,changes in lymph node short-axis before and after treatment,changes in tumor maximum diameter before and after treatment,lymph node type,and blood flow grade are associated with pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.Constructing a predictive model can help evaluate the pCR status of sentinel lymph nodes after neoadjuvant chemotherapy.

Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Objective To explore the factors associated with complete resolution of sentinel lymph node metastasis(pCR)after neoadjuvant chemotherapy in breast cancer and to establish a predictive model.Methods The medical records of 136 female patients with breast cancer who received neoadjuvant chemotherapy in the First Hospital of Lanzhou University from January 2022 to February 2024 were retrospectively analyzed.According to the 80/20 rule,the patients were randomly divided into a training set(108 cases)and a validation set(28 cases).Based on the pathological examination results of axillary lymph node dissection(ALND)after neoadjuvant chemotherapy in breast cancer patients,they were classified into the sentinel lymph node pCR group and non-pCR group.Multivariate logistic regression analysis was used to screen the independent risk factors of sentinel lymph nodes failing to reach pCR.Build a nomogram prediction model based on the screened risk factors.By drawing the receiver operating characteristic(ROC)curve calculation curve,the area under ROC curve,sensitivity and specificity are used to evaluate the discrimination of the model.Results Among the 108 breast cancer patients,46 cases achieved pCR in the sentinel lymph nodes,accounting for 42.59％(46 cases/108 cases).In addition,33 cases(30.56％)achieved pCR in the primary tumor lesion.The non-pCR group showed a higher proportion of stage Ⅲ clinical staging,lymph node short-axis reduction of less than 50％before and after treatment,tumor maximum diameter reduction of less than 50％before and after treatment,lymph node type Ⅲ classification,and blood flow grade Ⅲ compared to the pCR group(P＜0.05).Multivariate logistic regression analysis showed that Clinical staging(OR=3.593,95％CI:1.276-10.121),lymph node short-axis reduction of less than 50％before and after treatment(OR=4.272,95％CI:1.517-12.032),tumor maximum diameter reduction of less than 50％before and after treatment(OR=3.710,95％CI:1.317-10.449),lymph node type(OR=3.827,95％CI:1.359-10.779),and blood flow grade(OR=4.764,95％CI:1.691-13.418)were identified as risk factors for not achieving pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients(P＜0.05).The sensitivity of the risk model for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in the training set of breast cancer patients was 0.826(95％CI:0.705-0.943),with a specificity of 0.826(95％CI:0.712-0.919)and an area under the ROC curve of 0.847(95％CI:0.738-0.952).In the validation set,the sensitivity for predicting non-achievement of pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients was 0.731(95％CI:0.608-0.904),with a specificity of 0.827(95％CI:0.713-0.941)and an area under the ROC curve of 0.834(95％CI:0.729-0.951).Conclusion Clinical staging,changes in lymph node short-axis before and after treatment,changes in tumor maximum diameter before and after treatment,lymph node type,and blood flow grade are associated with pCR in the sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.Constructing a predictive model can help evaluate the pCR status of sentinel lymph nodes after neoadjuvant chemotherapy.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To analyze the factors associated with the effectiveness of home-based remote pulmonary rehabilita-tion(PR)in chronic obstructive pulmonary disease(COPD)patients.Method:Ninety stable COPD patients were selected and assessed with the social support rating scale(SSRS),6-minute walking test(6MWT),short form of health survey(SF-36)and lung function tests.Corre-lation analysis of SF-36 with SSRS was also performed.Result:The SSRS total score(P<0.001),SSRS subjective support score(P<0.001)and utilization of support score(P=0.038)were significantly higher in the high attendance group than in the low attendance group.The dif-ference between pre-treatment and post-treatment 6-minute walking distance(Δ6MWD)was significantly higher in the high attendance group than in the low attendance group(P<0.001);Role-Emotinal(RE)(P<0.001),Vitality(VT)(P<0.001),Mental Health(MH)(P<0.001),Social Functioning(SF)(P=0.01),Bodily Pain(BP)(P=0.012)and General Health(GH)(P=0.004)were significantly higher in the high attendance group than in the low attendance group in the SF-36.And the total score of the SSRS in the low attendance group had a significant positive cor-relation with Physical Functioning(PF)(r=0.265,P=0.043),Role-Physical(RP)(r=0.452,P<0.001),RE(r=0.513,P<0.001),VT(r=0.329,P<0.001),SF(r=0.469,P<0.001),BP(r=0.389,P=0.002),and GH(r=0.504,P<0.001)in the SF-36.Objective support scores of the SSRS in the low attendance group were significantly positively correlated with RE(r=0.391,P=0.002),BP(r=0.361,P=0.005),and GH(r=0.268,P=0.040)in the SF-36.Subjective support scores of the SSRS in the low attendance group were significantly positively correlated with RP(r=0.520,P<0.001),RE(r=0.342,P=0.008),VT(r=0.318,P=0.014),SF(r=0.402,P=0.002),and GH(r=0.446,P<0.001)in the SF-36.Utilization of support scores of the SSRS in the low attendance group was significantly positively correlated with RP(r=0.454,P<0.001),RE(r=0.313,P=0.016),SF(r=0.416,P=0.001),and GH(r=0.361,P=0.005)in the SF-36.The total score of the SSRS in the high attendance group was significantly positively correlated with VT(r=0.365,P=0.044)in the SF-36.And the subjective support of the SSRS in the high attendance group was signifi-cantly positively correlated with the PF(r=0.374,P=0.038)and SF(r=0.358,P=0.048)in the SF-36.Conclusion:Positive social support helps to increase participation in pulmonary rehabilitation,gain patients'en-ergy and relieve fatigue.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To analyze the physical activity level of patients treated with a percutaneous coronary intervention (PCI) for coronary artery disease in the early out-of-hospital recovery phase, and the factors influencing it.Methods:Patients who had been discharged within the previous 6 months after their first PCI treatment were surveyed using a general information questionnaire, the long form of the International Physical Activity Questionnaire (IPAQ), the Chinese version of the Tilburg Frailty Scale, the Social Support Rating Scale, and for their ability in the activities of daily living. Epidemiological descriptive methods were used to analyze the reported physical activity levels, and multifactoral logistic regression was applied to explore the influencing factors. The receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of the risk factors.Results:A total of 394 former patients were surveyed, including 117 (30%) reporting a low level of physical activity, 202 (51%) describing a moderate level and 75 (19%) claiming a high level. The univariate analysis revealed significant differences in physical activity levels among those of different ages, with different chronic co-morbidities, and with different frailty and self-care ability. Multifactoral logistic regression analysis showed that advanced age, chronic co-morbidities, frailty and little self-care ability are significant predictors of a low level of physical activity. The area under the ROC curve for predicting the physical activity level by combining those four factors was 0.89 (95% CI 0.84-0.94), with a sensitivity of 0.89 and a specificity of 0.80. Conclusions:The physical activity level of patients treated with PCI for coronary disease is moderately low early after their release from the hospital. Targeted intervention to increase it is called for.

Evidence mapping was used to systematically analyze the clinical research evidence of oral Chinese patent medicines in the treatment of intracerebral hemorrhage(ICH), thus revealing the distribution and quality of evidence in this field. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science from inception to July 5, 2024. The distribution characteristics of evidence were presented numerically and graphically. A total of 35 Chinese patent medicines were identified, involving 261 articles. The basic information of the 35 Chinese patent medicines, publication trend, traditional Chinese medicine(TCM) syndromes, interventions, and outcome indicators were compared and analyzed, and the methodological quality of the articles was evaluated. The results indicated that the clinical scope of Chinese patent medicines in the treatment of ICH was broad. However, the available studies inadequately emphasized the advantages and characteristics of TCM, lacked the safety information and the standards for evaluating outcome indicators, and paid insufficient attention to cognitive ability and neuropsychology. In addition, these articles demonstrated low quality. It is recommended that follow-up clinical research should be standardized and highlight the characteristics of TCM. In the analysis of outcome indicators, TCM syndrome evaluation should be taken as an important outcome indicator, and the evaluation criteria should be unified. Moreover, more attention should be paid to patients' cognitive ability and neuropsychology. The holder of marketing license of Chinese patent medicines should standardize the clinical position and improve the safety information in the medicine instructions according to the relevant requirements of the National Medical Products Administration. Additionally, the proportion of Chinese patent medicines in the category A list of medical insurance should be increased, and the limited medical resources should be rationally allocated.
Cerebral Hemorrhage/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Nonprescription Drugs/administration & dosage* ; Administration, Oral

This article aims to study the processing methods by exploring the main chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms. The relevant articles were retrieved from multiple databases with the time interval of 1960-2024, and the chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms of its processing methods were summarized. The review revealed that the chemical constituents of Aconiti Lateralis Radix Praeparata included 32 diester-type alkaloids, 36 monoester-type alkaloids, 43 alkanolamine-type alkaloids, and 8 lipid-type alkaloids. At the same time, other chemical constituents such as water-soluble alkaloids were also studied, and their pharmacological activities were summarized. The toxicity-attenuating mechanisms of the processing methods included constituent loss, hydrolysis, ester exchange, and ion-pair action. The processing methods of Aconiti Lateralis Radix Praeparata have developed from being traditional to modern, with simplified operation and increased retention amounts of active constituents, which have improved the efficacy of processed Aconiti Lateralis Radix Praeparata products and have facilitated the industrial production. However, the existing processing methods of Aconiti Lateralis Radix Praeparata cannot completely solve the problem of possible reduction in efficacy during toxicity attenuation. More toxicity-attenuating mechanisms and lipid-type alkaloids of Aconiti Lateralis Radix Praeparata should be explored, which is expected to reduce its toxicity while retaining its efficacy.
Aconitum/toxicity* ; Drugs, Chinese Herbal/isolation & purification* ; Alkaloids/chemistry* ; Animals ; Humans