Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.

Objective To establish a method for simultaneous determination of 14 components in Cinnamomi Cortex;To comprehensively evaluate its quality by multivariate statistical analysis technology.Methods HPLC method was used to establish the relative correction factors(RCF)between protocatechuic acid and 13 other components of coumalic acid,coumarin,cinnamyl alcohol,cinnamic acid,2-methoxycinnamic acid,cinnamaldehyde,o-methoxycinnamaldehyde,vanillic,syringic acid,4-hydroxybenzoic acid,procyanidin B2,epicatechin and procyanidin C1 to be measured,and the content of each component was calculated.The QAMS method was validated using external standard method(ESM),and the comprehensive quality of Cinnamomi Cortex was evaluated using PCA,OPLS-DA and EW-TOPSIS methods.Results The methodological verification results of ESM were in accordance with the requirements;the RCF established with protocatechuic acid as the reference had good durability under different experimental conditions,and the difference in content of each component between ESM and QAMS was not significant(P>0.05);the results of multivariate statistical analysis showed that accumulative contribution rate of former 2 principle components was 90.312%.Cinnamaldehyde,2-methoxycinnamic acid,procyanidin B2 and 4-hydroxybenzoic acid had a significant impact on the quality of Cinnamomi Cortex.The results of EW-TOPSIS showed that the Pi value of 16 batches of Cinnamomi Cortex ranged from 0.147 2 to 0.768 1.The quality of Cinnamomi Cortex from different producing areas varied greatly,and the overall quality of Cinnamomi Cortex from Guangxi Province was the best,followed by that from Guangdong Province and Yunnan Province,and the quality of Cinnamomi Cortex from Fujian Province was relatively poor.Conclusion The established QAMS multi-component quantitative method combined with multivariate statistical analysis technology can be used for comprehensive quality evaluation of Cinnamomi Cortex.

Drug loading is an important index to evaluate the quality of solid preparation of traditional Chinese medicine. Drug loading is restricted by drug characteristics, dosage form, process, and drug delivery in vivo, which affects the preparation process, therapeutic effect, and drug release rate. By consulting domestic and foreign literature, this paper put forward the significance of increasing the drug loading: improving the compliance of patients, reducing the production cost, reducing the risk of the excipients. In this review, the possible approaches to increase drug loading, such as the selection of high-efficiency excipients, suitable drug preparation techniques, and modification of the physical properties of drugs are summarized. It will provide theoretical basis through this review for the development of high drug loading and high-quality formulations.

Objective:To investigate the underlying neuroimaging mechanism of migraine without aura (MwoA) by using methods of voxel-based morphometry (VBM) and resting-state functional connectivity (FC).Methods:Twenty-five MwoA patients admitted to Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from September 2020 to June 2023 were recruited as MwoA group, and 22 volunteers were recruited as healthy control (HC) group. Demographic, clinical characteristics, scores of Hamilton Anxiety Scale (HAMA), Hamilton Depression Rating Scale (HAMD) and Montreal Cognitive Assessment (MoCA) of all subjects were collected; MwoA patients also received Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visual Analogue Scale assessments. All subjects underwent high-resolution 3D-T 1 and resting-state functional magnetic resonance imaging scanning. The SPM12 software was used to compare the difference in gray matter volume (GMV) between the 2 groups by VBM method. The GRETNA software was adopted to calculate the whole brain FC with anatomical automatic labeling 90 as the regions of interest, and the difference in FC between the 2 groups was statistically analyzed by two-sample t-test. Pearson partial correlation was used to analyze the correlation between brain GMV and FC changes and clinical features and scale scores of MwoA patients. Results:There existed no statistically significant difference between the 2 groups in age, gender, education, scores of HAMA, HAMD and MoCA (all P>0.05). Migraine Disability Assessment Questionnaire, Headache Impact Test-6 and headache Visua Analogue Scale scores of MwoA patients were (8.86±4.55), (50.27±6.35) and (6.68±1.73). Compared with the HC group, GMV was significantly decreased in the right superior frontal gyrus (SFG), right cingulate gyrus (CG) and left thalamus in the MwoA group ( P<0.05, false discovery rate corrected). In addition, the MwoA group showed decreased FC between left thalamus and right cuneus, left lingual gyrus (LG) and bilateral precuneus; decreased FC between right thalamus and right cuneus, right LG and right precuneus; decreased FC between right cuneus and left precuneus and right SFG; decreased FC between left LG and bilateral precuneus, decreased FC between right LG and right precuneus and left SFG; decreased FC between left precuneus and bilateral SFG, and between right precuneus and right SFG (edge P<0.001, component P<0.05, network-based statistics correction, interation=2 000). In MwoA patients, the FC (z-value) between left thalamus and right cuneus was negatively correlated with the duration of disease ( r=-0.530, P=0.011). Conclusions:MwoA patients showed decreased GMV in right SFG, CG and left thalamus. In MwoA patients, FC between thalamus and visual network (VN) and default mode network (DMN) was significantly decreased, and FC among VN, DMN and executive control network was significantly decreased. These changes in brain structure and function may be an adaptive change in the central sensitivity and responsiveness to pain stimuli, and may be an important neuroimaging mechanism of MwoA.

Objective:To investigate the differences in resting-state functional connectivity (FC) between patients with vestibular migraine (VM) and migraine without aura (MwoA) in order to infer the possible neuroimaging mechanisms of VM.Methods:Thirty VM patients admitted to the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from December 2019 to December 2022 were selected as the experimental group (EG) (6 males and 24 females, with mean age of 38.3 years) and 26 MwoA patients as the control group (7 males and 19 females, mean age 35.5 years). General demographic and clinical data such as gender, age, year of education, course of disease and frequency of attacks were collected for all the patients, as well as data of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), headache Visual Arialogue Scale (VAS), Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment Questionnaire (MIDAS). VM patients were also assessed by Dizziness Handicap Inventory (DHI), dizziness VAS and Vestibular Disorders Activities of Daily Living (VADL) scales. All patients underwent resting-sate functional Magnetic Resonance Imaging (fMRI) scans. Bilateral parietal opercular cortex 2 (OP2) and primary visual cortex (V1) were used as regions of interests (ROIs). Differences in FC between ROIs and other brain regions were calculated between the two groups. In view of the brain regions with significant differences, z-values of FC were extracted for each subject in the EG, and Pearson partial correlation analysis was conducted between z-values of FC and clinical characteristics of patients, P<0.05 was considered to have significant correlation. SPSS 22.0 was used for statistical analysis. Results:There was no significant difference in gender, age, years of education, course of disease, frequency of attack and scores of MoCA, HAMA and HAMD between the two groups ( P>0.05). Headache VAS, HIT-6 and MIDAS scores in VM patients were significantly lower than those in MwoA patients ( P<0.05). Compared with MwoA patients, the FC between left OP2 and bilateral precuneus and left thalamus was significantly increased in VM patients, and the FC between right OP2 and left thalamus and right anterior cingulate gyrus were significantly increased ( P<0.05, False Discovery Rate correction). Correlation analysis showed that the FC between left OP2 and left precuneus was positively correlated with DHI score in VM patients ( P=0.007, r=0.480), and the FC between right OP2 and left thalamus was positively correlated with the disease course in VM patients ( P=0.015, r=0.439). Conclusions:The pathogenesis of VM may be related to the altered FC of vestibular, pain and visual-motor networks, abnormalities of these neural pathways may be important imaging biomarkers of VM pathogenesis.

Objective:To investigate the association of monocyte to lymphocyte ratio (MLR) with all-cause mortality and cardiovascular disease (CVD) mortality in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a retrospective cohort study. The clinical data of 495 incident CAPD patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The optimal cut-off value of baseline MLR was determined by the receiver operating characteristic (ROC) curve for predicting all-cause death in the first year of CAPD, and then the patients were divided into high MLR group and low MLR group. The differences of clinical data and laboratory tests were compared between the two groups. The endpoint events were death (all-cause death and CVD death), conversion to hemodialysis, conversion to kidney transplantation, or follow-up until March 31, 2020. The survival curve was drawn by the Kaplan-Meier method, and the Log-rank test was used to compare the survival difference between the two groups. A Cox regression model was established to analyze the relevant factors of all-cause mortality and CVD mortality in CAPD patients.Results:The study included 495 patients, with age of (43.79±12.16) years and 308 (62.22%) males. The median age of dialysis was 17(10, 30) months. By the end of follow-up, 61(12.32%) of 495 patients had died, 51(10.51%) had been converted to hemodialysis, and 28(5.66%) had been converted to kidney transplantation. Of the 61 patients who died, 36(59.02%) died of cardiovascular events. ROC curve analysis results showed that the optimal cut-off value was 38.24%, so there were 246 cases in the high MLR group (MLR>38.24%) and 249 cases in the low MLR group (MLR≤38.24%). The all-cause mortality rates were 6.83% in the low MLR group and 17.89% in the high MLR group, and the CVD mortality rates were 3.21% in the low MLR group and 11.38% in the high MLR group, respectively. The Kaplan-Meier survival curve showed that the survival rate of the low MLR group was significantly higher than that of the high MLR group (all-cause mortality, Log-rank χ2=18.369, P<0.001; CVD mortality, Log-rank χ2=16.142, P<0.001). Using all-cause death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 89.4% and 79.9%, respectively, with a median survival time of 64 months in the low MLR group. The 1-year, 3-year and 5-year cumulative survival rates were 95.0%, 68.3% and 49.6%, respectively, with a median survival time of 54 months in the high MLR group. Using CVD death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 95.2% and 91.2%, respectively, with a median survival time of 69 months in the low MLR group. The 1-year, 3-year, and 5-year cumulative survival rates were 97.8%, 78.6%, and 60.8%, respectively, with a median survival time of 60 months in the high MLR group. Multivariate Cox regression analysis showed that MLR was independently associated with all-cause mortality ( HR=2.744, 95% CI 1.484-5.075, P=0.001) and CVD death ( HR=3.249, 95% CI 1.418- 7.443, P=0.005) in CAPD patients. According to the competing risk model analysis, MLR was still independently associated with all-cause mortality and CVD mortality in CAPD patients. Conclusion:MLR is associated with all-cause mortality and CVD mortality in CAPD patients, and can be used as a valuable indicator for judging the prognosis of CAPD patients.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

Objective:To compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients without diabetes mellitus and identify related influencing factors.Methods:Patients who started hemodialysis with an arteriovenous graft or fistula or PD in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to February 1,2019 were included. They were followed up until May 1, 2019. The patients were divided into HD group and PD group according to the initial dialysis modality. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate influence factors for survival rates, and the inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups.Results:There were 371 patients with maintenance dialysis enrolled in this study, including 113 cases (30.5%) in HD group and 258 cases (69.5%) in PD group. At baseline, the scores of standard mean difference ( SMD) in age, body mass index (BMI), combined with cerebrovascular disease, Charlson comorbidity index (CCI), blood potassium, plasma albumin and hemoglobin between the two groups were greater than 0.1. The score of SMD decreased after IPTW, and the most data were less than 0.1, which meant that the balance had been reached between the two groups. The Kaplan-Meier survival curve showed that the cumulative survival rates had no significant difference for all-cause death before using IPTW between the two groups (Log-rank χ2=0.094, P=0.759). After adjusting for confounders with IPTW, the Kaplan-Meier survival curve showed that the cumulative survival rates still had no significant difference for all-cause death between the two groups (Log-rank χ2=2.090, P=0.150). Univariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus for all-cause death (PD/HD, HR=1.171, 95% CI 0.426-3.223, P=0.760). Multivariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus (PD/HD, HR=1.460, 95% CI 0.515-4.144, P=0.477), and high plasma albumin ( HR=0.893, 95% CI 0.813-0.981, P=0.019) was an independent protective factor for survival in ESRD patients without diabetes mellitus. There was still no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus after using IPTW (PD/HD, HR=1.842, 95% CI 0.514-6.604, P=0.348). Conclusion:The difference of cumulative survival rates between HD and PD is not significant in ESRD patients without diabetes mellitus.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.