Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

BACKGROUND: Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis. METHODS: We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results. RESULTS: We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9. CONCLUSION This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Female ; Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Neoplasms, Hormone-Dependent ; Reproducibility of Results ; Endometrial Neoplasms ; Lupus Erythematosus, Systemic/genetics* ; Carcinoma, Endometrioid ; Breast Neoplasms ; Polymorphism, Single Nucleotide

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

Objective:The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively.Methods:A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis.Results:The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively ( P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively ( P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion:The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

Objective:To evaluate the value of a novel multiphase three-dimensional deep learning neural network of computer-aided diagnosis (CAD) used in LDCT lung cancer screening.Methods:Eight thousand eight hundred and fifty volunteers with 1 111 nodules were enrolled in the lung cancer screening from November of 2013 to December of 2017, and the baseline LDCT imaging data of volunteers accompanied with clinical information were retrospectively analyzed. All volunteers in this study were designed to receive LDCT test at least once. All the imaging of volunteers were read through the methods of visual detectioin (VD), CAD, and VD Combined CAD. The criteria of the true pulmonary nodule was determinated by the consistent opinion of two specialists in chest imaging（in case of disagreement, the decision should made by the third chief physician). In terms of the numbers, types or Lung-RADS categories of nodules, the detection rate, missed diagnosis rate and false positive rate of pulmonary nodules or lung cancer among three methods were compared, and the rates between groups were compared by χ 2test. Results:Compared with VD or CAD ,the detection rate of nodules in the CAD combined VD was significantly increased (95.7% , 94.2%, vs. 80.1% P<0.05 ), and the rate of missed diagnosis was significantly reduced (5.8%, 4.3% vs. 19.9% ，χ2=101.650, 128.500 ，P<0.05); Compared with VD, the methods of CAD or VD combined CAD significantly increased the the detection rates of Lung-RADS categories (χ2 =25.083,23.449, P=0.000, 0.000) or different types of nodules (χ2=6.955,6.821, P=0.031, 0.033), but there was no statistically significant difference between CAD and VD combined CAD for Lung-RADS categories and different types of nodules (all P>0.05); Compared with VD and VD combined CAD, the positive prediction rate of CAD for lung cancer was significantly reduced, and the rate of missed diagnosis and false positive rate were significantly increased, but there was no significant difference between VD and VD combined CAD in the prediction rate, missed diagnosis rate and false positive rate of lung cancer. Conclusion:The method of CAD combined VD can reduce the detection of false positive nodules and improve the detection rate of true pulmonary nodules,which is the preferred method using in LDCT lung cancer screening for city population.

Objective: To evaluate the potential clinical value of standardized procedures of fine lymph node sorting from gastric can-cer samples after curative resection. Methods: Between January 2016 and December 2017, 727 gastric cancer patients who under- went R0 resection in the Tianjin Medical University Cancer Institute and Hospital were retrospectively included and assigned to either the fine lymph node sorting group or regional lymph node sorting group in accordance with the lymph node sorting methods from the tumor samples of all patients. Both the numbers of examined lymph nodes and metastatic lymph nodes were compared between the two groups. Additionally, correlation analyses were performed between the numbers of examined lymph nodes and metastatic lymph nodes in the two groups. Results: There was no significant difference in sex, age, or tumor size between the two groups (P>0.05), indi-cating that there was comparability between the two groups. The number of examined lymph nodes in the fine lymph node sorting group was significantly higher than that in the regional lymph node sorting group (P<0.001). Furthermore, the number of examined lymph nodes in the fine lymph node sorting group was much higher than that in the regional lymph node sorting group with the same pT, pN, or pTNM stage (P<0.001). The number of metastatic lymph nodes in the fine lymph node sorting group was significantly higher than that in the regional lymph node sorting group (P<0.001). There was a significant positive correlation between the numbers of ex-amined lymph nodes and metastatic lymph nodes in both groups (fine lymph node sorting group r=0.181, P=0.023; regional lymph node sorting group r=0.227, P<0.001). Additionally, the correlation coefficient between the numbers of examined lymph nodes and metastatic lymph nodes in the fine lymph node sorting group was weaker than that in the regional lymph node sorting group. Conclu-sions: The standard procedures of fine lymph node sorting from tumor samples of gastric cancer may increase the number of exam-ined lymph nodes, accurately provide the postoperative pN stage, reduce the stage migration, and should be applied in clinical stan-dardization.

OBJECTIVE Construct and validate the EGFR-CART (Epidermal growth factor receptor-chimeric antigen receptor T) cells targeting the Fadu cell line of hypopharyngeal squamous cell carcinoma, and provide the preclinical basis for the application of CART cell technology in hypopharyngeal squamous cell carcinoma. METHODS EGFR-CART cells and CART-control cells were constructed by lentivirus transfection. The expression of EGFR antibody in CART cells was detected by FACS fluorescence detection, and the expression of EGFR in Fadu cell line and HCT-116 cell line was verified. RESULTS EGFR-CART cells and CART-control cells were successfully constructed, the infection efficiency was about 67％, and there was no significant difference between the two groups in the distribution of cell subsets. HCT-116 is selected as the non target cells of EGFR-CART, Fadu as target cell. CONCLUSION In this study, we successfully prepared and validated the EGFR-CART cells targeting the Fadu cell line of hypopharyngeal squamous cell carcinoma, and laid the foundation for the application of CART technique in the treatment of hypopharyngeal carcinoma.

OBJECTIVETo investigate the clinicopathological characteristics, diagnosis, treatment and prognosis of patients with primary gastric adenosquamous cell carcinoma.

METHODSA total of 5 562 patients with gastric neoplasm were admitted in Tianjin Medical University Cancer Institute and Hospital from January 2001 to January 2011. Among them 42 patients were diagnosed as primary gastric adenosquamous cell carcinoma, accounting for 0.76% of all the patients. The clinicopathological and follow-up data of these 42 patients with primary gastric adenosquamous cell carcinoma were retrospectively analyzed, and Cox proportional hazard model was used to analyze the prognostic factors of gastric adenocarcinoma squamous cell carcinoma.

RESULTSAmong above 42 patients, 32 were male and 10 were female, with a male-to-female ratio of 3.2/1.0 and the average age was 63 years (range: 46 to 77 years). Five patients (11.9%) were confirmed as adenosquamous cell carcinoma by preoperative pathological examination, while other 37 patients were diagnosed as adenocarcinoma preoperatively. According to the 7th edition AJCC TNM classification system for gastric adenocarcinoma, 5 patients (11.9%) were in stage II(, 30 patients (71.4%) in stage III( and 7 patients (16.7%) in stage IIII(. The maximum tumor diameter was > 5 cm in 18 patients (42.9%). Borrmann type III(-IIII( was found in 29 patients (69.0%), and poorly differentiated (or undifferentiated) tumor was found in 32 patients (76.2%). Radical operations were performed in 31 patients (73.8%), the reasons of non radical operations included infiltration of pancreas in 3 patients, infiltration of radices mesocili transvers in 1 patient and classification of stage IIII( in 7 patients. Lymph node dissection was performed in 37 patients, 83.8% of them (31/37) was found with lymphatic metastases. Twenty-five patients received adjuvant chemotherapy except for 7 patients in stage IIII( and 10 patients who refused adjuvant chemotherapy. All the patients had an average survival time of 36.4 months and median survival time of 28.0 months, and the overall 1-, 3- and 5-year survival rates were 82.2%, 42.3% and 18.2% respectively. Univariate analysis revealed that tumor size (χ=4.039, P=0.044), Borrmann type (χ=18.728, P=0.000), tumor differentiation (χ=19.612, P=0.000), radical gastectomy (χ=41.452, P=0.000), lymph node metastasis (χ=9.689, P=0.002) and clinical stage (χ=26.277, P=0.000) were associated with postoperative survival. Multivariate analysis revealed that tumor differentiation (HR=10.560, 95%CI:2.263-49.281, P=0.003), radical gastrectomy (HR=4.309, 95%CI:1.311-14.168, P=0.016) and clinical stage (HR=2.392, 95%CI:1.022-5.600, P=0.044) were independent prognosis factors.

CONCLUSIONSPrimary gastric adenosquamous cell carcinoma is rare with poor prognosis. Radical gastrectomy is recommended. Tumor differentiation, radical gastrectomy and clinical stage are important indicators to evaluate prognosis of primary gastric adenosquamous cell carcinoma.

Adenocarcinoma ; diagnosis ; mortality ; pathology ; therapy ; Aged ; Carcinoma, Squamous Cell ; diagnosis ; mortality ; pathology ; therapy ; Chemotherapy, Adjuvant ; statistics & numerical data ; Female ; Gastrectomy ; methods ; statistics & numerical data ; Humans ; Lymph Node Excision ; statistics & numerical data ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; statistics & numerical data ; Neoplasm Invasiveness ; pathology ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; mortality ; pathology ; therapy ; Survival Rate