Objective This study aimed to explore the potential targets of Yishenqingli Formula in treating idiopathic membranous nephropathy(IMN)using a combination of liquid chromatography-mass spectrometry(LC-MS)analysis and network pharmacology.Methods The active ingredients of the Yishen Qingli Formula were identified through the BATMAN-TCM database and LC-MS qualitative analysis.The biological processes and mechanism pathways of the Yishen Qingli Formula in treating IMN were predicted using network pharmacology,and molecular docking and in vitro,experiments were conducted to verify the selected core targets.The core targets were selected and validated through molecular docking and in vitro experiments.Results A total of 15 active ingredients were selected from the Yishen Qingli Formula,and 72 core genes were obtained by intersecting its target with the IMN disease target.GO enrichment analysis results showed that the regulation of apoptosis signaling pathway,white cell migration,peptide tyrosine phosphorylation,and so on were involved;The KEGG pathway enrichment analysis results showed that the treatment of IMN with Yishen Qingli Formula involves apoptosis-related signaling pathways such as TNF,PI3K/AKT,MAPK,etc.In vitro,experiments have shown that Yishen Qingli Formula can reduce podocyte apoptosis by regulating the PI3K/AKT pathway.Conclusion Yishen Qingli Formula is a treatment for idiopathic membranous nephropathy through multiple targets and pathways.It has an anti-apoptotic effect on the C5b-9 induced podocyte sub-lysis model,and its mechanism of action may be related to the TNF,PI3K/AKT,MAPK signaling pathways.

Background: Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. Methods: Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. Results: In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4–8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. Conclusions Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.

OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Objective:To explore the predictive value of complement and coagulation indicators in sepsis related acute kidney injury (AKI).Methods:Clinical data of 217 patients with sepsis admitted to the Department of Internal Medicine and Intensive Care Unit of Affiliated Hospital of Jiangnan University from January 2018 to June 2019 were retrospectively analyzed. All patients were divided into sepsis with AKI group and without AKI group. Laboratory indicators of all patients were collected, including complement C 3, complement C 4, activated partial thrombin time (APTT), prothrombin time (PT), international normalized ratio (INR), D-dimer, procalcitonin(PCT), etc. logistic regression analysis was used to explore the risk factors of sepsis related AKI. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of independent risk factors. Results:Among 217 patients, 120 patients developed sepsis related AKI and 97 patients didn′t. PCT, lactic acid, PT, APTT, INR and D-dimer in AKI patients were significantly higher than those without AKI ( P<0.01). Complement C 3 and complement C 4 were significantly lower in AKI group ( P<0.01). Multivariate logistic regression analysis suggested that blood pressure<90/60 mmHg (1 mmHg=0.133 kPa)( OR=3.705, 95% CI 1.536-8.934, P=0.004), increased lactic acid ( OR=1.479, 95% CI 1.089-2.008, P=0.012), decreased complement C 3 ( OR=0.027, 95% CI 0.005-0.152, P<0.001) and prolonged APTT ( OR=1.090, 95% CI 1.047-1.137, P<0.001)were independent risk factors predicting AKI. The area under the ROC curve (AUC) of these multivariates were 0.741 (95% CI 0.675-0.807), 0.798 (95% CI 0.732-0.864), 0.712 (95% CI 0.643-0.781) and 0.716 (95% CI 0.648-0.783) respectively. The relevant sensitivity was 57.5%, 80.8%, 87.5%, 59.2%, and the specificity was 90.7%, 75.3%, 51.5%, 77.3%, respectively. The AUC of the combined four indicators was 0.880 (95 %CI 0.835-0.926) with the sensitivity 75.0% and the specificity 90.7%. Conclusion:The low level of complement C 3 and prolonged APTT predict sepsis related AKI, and the predictive value can be enhanced if hypotension and hyperlactacidemia are added.

Objective: To investigate the distribution patterns of 21-gene assay and its influencing factors in Chinese patients with early breast cancer. Methods: Nine hundred and twenty-seven early breast cancer patients were retrospectively recruited from January 2009 to December 2015 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The 21-gene reverse transcriptase-polymerase chain reaction(RT-PCR) assay were conducted in paraffin-embedded tumor tissues to calculate the Recurrence Score(RS). Immunohistochemistry(IHC) assay was used to measure the expression levels of estrogen receptor(ER), progesterone receptor(PR) and Ki-67. Concordances of RT-PCR and IHC results were assessed. Correlations of RS and classical clinicopathological factors were evaluated, and logistic regression were applied to determine independent predictive factors for RS. Results: The median RS of 927 patients was 23(range: 0~90), and the proportions of patients categorized as having a low, intermediate, or high risk were 26.5%, 47.7% and 25.8%, respectively. The distribution of RS varied significantly according to different tumor grade, T stage, PR status, Ki-67 index and molecular subtypes(P<0.05 for all). Grade, PR status and Ki-67 index were independent predictive factors for RS. ER, PR status and Ki-67 index showed significantly correlation between RT-PCR and IHC assays, and the concordance rates for ER and PR status were 98.7% and 87.8%, respectively. Conclusions RS significantly correlated with tumor grade, T stage, PR status, Ki-67 index and subtypes. Grade, PR status and Ki-67 index can independently predict RS. Remarkable concordances of ER, PR status and Ki-67 index are found between RT-PCR and IHC assays.

Objective: To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods: One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results: After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.

Objective To analyze the applied condition of ovary function suppression ( OFS) before and after joint analysis of TEXT and SOFT trials and SOFT trial, and to identify the relevant factors of OFS usage. Methods The analysis was performed in premenopausal women with hormone receptor ( HR ) positive breast cancer receiving surgical treatment from Apr 2013 to Oct 2015 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine. Adjuvant treatment strategy was made in the multidisciplinary team ( MDT) meetings. We analyzed the applied condition of OFS before and after joint analysis, SOFT trial and its relevant factors. Results Among 454 patients, 114 (25.1%) patients received OFS. Before the results of joint analysis came out, all the patients ( 38/38) received OFS together with tamoxifen ( TAM);after the results came out, clinicians began to put OFS with exemestane into practice, among 76 patients, 41(53.9%) patients received OFS with exemestane while 35 (46.1%) patients received OFS together with TAM. Before the results of SOFT trial came out, 71 out of 310 (22.9%) patients received OFS while 43 out of 144 (29.9%) patients received OFS after that. No significant difference was found between the proportion of patients receiving OFS before and after the results of SOFT trial came out ( P=0.112) . Age, histological grade, pN status, Ki?67 status, molecular subtype and acceptance of chemotherapy were correlated with OFS treatment (P<0.05). Age, tumor grade and pN were independent significant predictors of OFS usage. Conclusions After the results of joint analysis came out, clinicians began to apply OFS with exemestane to premenopausal women with HR positive breast cancer. There is no significant difference between the proportion of patients receiving OFS before and after SOFT trial. Age, tumor grade and pN status are independent significant predictors of OFS treatment. Patients younger than 40, with histological grade Ⅱ or Ⅲ tumor and with pN1 or pN2 status are prone to receive OFS.

Objective To analyze the applied condition of ovary function suppression ( OFS) before and after joint analysis of TEXT and SOFT trials and SOFT trial, and to identify the relevant factors of OFS usage. Methods The analysis was performed in premenopausal women with hormone receptor ( HR ) positive breast cancer receiving surgical treatment from Apr 2013 to Oct 2015 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine. Adjuvant treatment strategy was made in the multidisciplinary team ( MDT) meetings. We analyzed the applied condition of OFS before and after joint analysis, SOFT trial and its relevant factors. Results Among 454 patients, 114 (25.1%) patients received OFS. Before the results of joint analysis came out, all the patients ( 38/38) received OFS together with tamoxifen ( TAM);after the results came out, clinicians began to put OFS with exemestane into practice, among 76 patients, 41(53.9%) patients received OFS with exemestane while 35 (46.1%) patients received OFS together with TAM. Before the results of SOFT trial came out, 71 out of 310 (22.9%) patients received OFS while 43 out of 144 (29.9%) patients received OFS after that. No significant difference was found between the proportion of patients receiving OFS before and after the results of SOFT trial came out ( P=0.112) . Age, histological grade, pN status, Ki?67 status, molecular subtype and acceptance of chemotherapy were correlated with OFS treatment (P<0.05). Age, tumor grade and pN were independent significant predictors of OFS usage. Conclusions After the results of joint analysis came out, clinicians began to apply OFS with exemestane to premenopausal women with HR positive breast cancer. There is no significant difference between the proportion of patients receiving OFS before and after SOFT trial. Age, tumor grade and pN status are independent significant predictors of OFS treatment. Patients younger than 40, with histological grade Ⅱ or Ⅲ tumor and with pN1 or pN2 status are prone to receive OFS.

OBJECTIVESTo study the factors influencing the non-sentinel lymph node(NSLN) status and to assess performance of Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram in predicting sentinel lymph node(SLN) metastases in a SLN positive Chinese breast cancer population.

METHODSData were collected from breast cancer patients who were diagnosed with pathological positive sentinel lymph node and received further axillary lymph node dissection(ALND) in Shanghai Ruijin Hospital from January 2011 to August 2014. MSKCC nomogram was used to calculate each patient's NSLN metastasis risk score. The receiver operator characteristic curve (ROC curve) and the area under the ROC curve (AUC) was used to assess the predictive accuracy of the model.

RESULTSAmong the 1 147 patients who received sentinel biopsy, 150 SLN positive patients who received ALND were enrolled in this study. By univariate analysis, multifocal breast cancer (χ(2)=5.887, P=0.015), SLN+ /SLN ratio (χ(2)=6.683, P=0.010) and abnormal axillary lymph node displayed by ultrasound (χ(2)=7.736, P=0.005) were the influencing factors of NSLN metastases. By multivariate analysis, multifocal breast cancer (OR=7.25, 95% CI: 1.73 to 30.43, P=0.007), SLN+ /SLN ratio ≥ 0.5 (OR=2.564, 95% CI: 1.22 to 5.39, P=0.013) and abnormal axillary lymph node displayed by ultrasound (OR=2.471, 95% CI: 1.18 to 5.19, P=0.017) were the independent influencing factors of NSLN metastases. The AUC of MSKCC nomogram in this population was 0.677.

CONCLUSIONSFor breast cancer patients with positive sentinel lymph node, multifocality, SLN+ /SLN ratio and axillary lymphadenopathy displayed by ultrasound is related to NSLN metastasis. MSKCC has low accuracy in predicting NSLN status of this population.

Area Under Curve ; Axilla ; Breast Neoplasms ; China ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Nomograms ; ROC Curve ; Risk Factors ; Sentinel Lymph Node Biopsy

Objective A phase Ⅱ trial of anti-programmed death-1 (PD-1) monoclonal antibody CT-011,an anti PD-1 humanized monoclonal antibody combined with rituximab therapy in patients with relapsed follicular lymphoma (FL) were conducted.Methods In order to evaluate the safety and efficacy of CT-011,the impacts of CT-011 on immune cells both from the peripheral blood (PB) samples and tumor microenvironment were examined.PB and core needle biopsies from involved lymph nodes were collected prior to and on day 14 after the first infusion of CT-011.PB mononuclear cells (PBMC) were analyzed by multiparametric flow cytometry to determine various immune cell subsets.Whole genome gene expression profiling (GEP) was performed on core needle biopsies.Results A significant increase in the absolute number of PB immune cells were observed in day 14 samples compared with baseline including total lymphocyte count (P ＜ 0.01),CD+3 T cells (P =0.01),CD+4 T cells (P ＜ 0.01).Comparison of GEP from core needle biopsies obtained pretreatment and day 14 (n =8 pairs) showed up regulation of several genes associated with T cell activation.Conclusion Administration of CT-011 was associated with increase in the numbers of CD+4 T cells and resulted in activation of T cells in the PB and the tumor microenvironment in FL.These results provide insight into the mechanism of action of CT-011 and offer a predictive biomarker for selection of patients for future clinical trials with this class of agents in FL.