Objective To analyze the literature of leech in medicine using CiteSpace knowledge map,comprehensively understand the research status,hotspots and development trends of component analysis and pharmacological effects of leech,and provide reference for researchers in the field of leech.Methods CiteSpace 6.1 R3 software was used to analyze the relevant literature of leech in the field of medical research in CNKI and Web of Science databases from 1996 to 2022.The bibliometric and visual analysis of the number of articles,authors,research institutions,keyword co-occurrence,clustering and emergence were carried out.Results A total of 1 115 Chinese articles in CNKI database and 237 English articles in Web of Science database were included.The analysis of Chinese and English literature showed that the author Shi Hongzhuan had the largest number of Chinese articles,and the German author Hildebrandt had the largest number of English articles.Shandong University of Traditional Chinese Medicine and Chinese Academy of Sciences were the institutions with the largest number of articles in Chinese and English respectively.The country with the most published English literature is the United States.Chinese and English keyword co-occurrence and cluster analysis showed that Chinese literature focused on the study of its active ingredient hirudin,including molecular structure,pharmacological efficacy,mechanism of treating thrombosis,coronary heart disease,kidney disease and other diseases,and paid attention to the differences in the active ingredients of different types of leeches.In addition,English literature focused on the clinical external use of living leeches.The emergence of keywords suggested that the mechanism of action,the search and synthesis of hirudin analogues,and the pharmacodynamic mechanism of compatibility application were not only the current research hotspots,but also the future hot spots.Conclusion The analysis of leech components,the pharmacological mechanism of leech in the treatment of cardiovascular diseases,chronic kidney diseases and other diseases have always been the research hotspots.Hirudin analogues,the pharmacodynamic mechanism of compatibility application,network pharmacology,molecular docking and so on may be the future research hotspots and trends of leeches.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

This study delves into the pivotal factors influencing the consensus process within traditional Chinese medicine guideline development, with the objective of augmenting the quality of this process through methodological recommendations aimed at elevating standardization.

Objective:This study aimed to explore the clinical application value of the indication selection criteria for bi-pedicled deep inferior epigastric arterial perforator flap(DIEP) versus pedicled transverse rectus abdominis myocutaneous flap(TRAM) combined with DIEP for breast reconstruction.Methods:The clinical data of patients who underwent delayed bi-pedicled abdominal flap breast reconstruction after breast cancer surgery in the Department of Oncoplastic and Reconstructive Breast Surgery and Department of Mammoplasty, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2008 to April 2022 were retrospectively analyzed. According to the indications for each procedure, corresponding blood supply source was selected. Subsequently, patients were divided into two groups: bi-pedicled DIEP group and pedicled TRAM+ DIEP combined flap group according to the type of blood supply source. The indication selection criteria for pedicled TRAM+ DIEP combined flap was as follows: lack of two groups of recipient vessels; no dominant perforator in the abdominal donor site; previous abdominal liposuction or abdominal surgery with large dissection range and severe scar; patients were unable to tolerate prolonged surgery or had high risk factors for microsurgery. A comparison of breast reconstruction surgery characteristics was conducted between the two groups. Independent-samples t-test, rank sum test, Chi-square test and Fisher’s exact probability method were used to analyze various data including age, body mass index (BMI), time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy, history of chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length, preoperative and postoperative conditions, as well as postoperative complications. Statistical significance was defined at P<0.05. Results:A total of 54 patients who underwent unilateral breast reconstruction were included in this study with a mean age of 42.2 years (range, 30-59 years). The pedicled TRAM+ DIEP combined flap group consisted of 21 patients with a mean age of 42.7 years (range, 33-56 years) while the bi-pedicled DIEP group comprised 33 patients with a mean age of 41.8 years (30-59 years). Out of the 54 patients, a total of 38 were eventually followed up, comprising 14 in the pedicled TRAM+ DIEP combined flap group and 24 in the bi-pedicled DIEP group. The average follow-up duration for the pedicled TRAM+ DIEP combined flap group was 42 months (range, 6-69 months). Abdominal bulge occurred in one patient, while another patient experienced abdominal hernia. The average follow-up duration for the bi-pedicled DIEP group was 47 months (6-179 months), with no reported cases of abdominal bulge or abdominal hernia. There were no statistically significant differences observed between the two groups regarding age, BMI, time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy or chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length or time to ambulation (all P>0.05). However, there was a statistically significant difference noted in duration of surgery between the pedicled TRAM+ DIEP combined flap group and bi-pedicled DIEP group [6.0(5.5-6.5) hours vs. 8.5(8.0-8.8) hours] ( P<0.01). Comparison analysis revealed no statistically significant differences in terms of partial flap necrosis (0/21 vs. 1/33), abdominal incision dehiscence (2/21 vs. 2/33), abdominal bulge (1/14 vs. 0 /24) or abdominal hernia (1/1 vs. 0/24) between the two groups ( P>0.05). Conclusion:For patients who needed bilateral vascular pedicled lower abdominal wall for breast reconstruction, utilizing a pedicled TRAM+ DIEP combined flap did not increase surgical complication risks. The proposed indication selection criteria for using a pedicled TRAM + DIEP combined flap outlined in this study could serve as guidance when choosing methods for bi-pedicled abdominal flap breast reconstruction.

Objective:This study aimed to explore the clinical application value of the indication selection criteria for bi-pedicled deep inferior epigastric arterial perforator flap(DIEP) versus pedicled transverse rectus abdominis myocutaneous flap(TRAM) combined with DIEP for breast reconstruction.Methods:The clinical data of patients who underwent delayed bi-pedicled abdominal flap breast reconstruction after breast cancer surgery in the Department of Oncoplastic and Reconstructive Breast Surgery and Department of Mammoplasty, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2008 to April 2022 were retrospectively analyzed. According to the indications for each procedure, corresponding blood supply source was selected. Subsequently, patients were divided into two groups: bi-pedicled DIEP group and pedicled TRAM+ DIEP combined flap group according to the type of blood supply source. The indication selection criteria for pedicled TRAM+ DIEP combined flap was as follows: lack of two groups of recipient vessels; no dominant perforator in the abdominal donor site; previous abdominal liposuction or abdominal surgery with large dissection range and severe scar; patients were unable to tolerate prolonged surgery or had high risk factors for microsurgery. A comparison of breast reconstruction surgery characteristics was conducted between the two groups. Independent-samples t-test, rank sum test, Chi-square test and Fisher’s exact probability method were used to analyze various data including age, body mass index (BMI), time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy, history of chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length, preoperative and postoperative conditions, as well as postoperative complications. Statistical significance was defined at P<0.05. Results:A total of 54 patients who underwent unilateral breast reconstruction were included in this study with a mean age of 42.2 years (range, 30-59 years). The pedicled TRAM+ DIEP combined flap group consisted of 21 patients with a mean age of 42.7 years (range, 33-56 years) while the bi-pedicled DIEP group comprised 33 patients with a mean age of 41.8 years (30-59 years). Out of the 54 patients, a total of 38 were eventually followed up, comprising 14 in the pedicled TRAM+ DIEP combined flap group and 24 in the bi-pedicled DIEP group. The average follow-up duration for the pedicled TRAM+ DIEP combined flap group was 42 months (range, 6-69 months). Abdominal bulge occurred in one patient, while another patient experienced abdominal hernia. The average follow-up duration for the bi-pedicled DIEP group was 47 months (6-179 months), with no reported cases of abdominal bulge or abdominal hernia. There were no statistically significant differences observed between the two groups regarding age, BMI, time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy or chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length or time to ambulation (all P>0.05). However, there was a statistically significant difference noted in duration of surgery between the pedicled TRAM+ DIEP combined flap group and bi-pedicled DIEP group [6.0(5.5-6.5) hours vs. 8.5(8.0-8.8) hours] ( P<0.01). Comparison analysis revealed no statistically significant differences in terms of partial flap necrosis (0/21 vs. 1/33), abdominal incision dehiscence (2/21 vs. 2/33), abdominal bulge (1/14 vs. 0 /24) or abdominal hernia (1/1 vs. 0/24) between the two groups ( P>0.05). Conclusion:For patients who needed bilateral vascular pedicled lower abdominal wall for breast reconstruction, utilizing a pedicled TRAM+ DIEP combined flap did not increase surgical complication risks. The proposed indication selection criteria for using a pedicled TRAM + DIEP combined flap outlined in this study could serve as guidance when choosing methods for bi-pedicled abdominal flap breast reconstruction.

Objective: To explore the effects of red LEDs on the proliferation and osteogenic differentiation of human stem cells from apical papilla (hSCAPs). Methods: hSCAPs were obtained by isolation, culture and flow cytometry in vitro and irradiated with 1, 3, 5, and 7 J/cm2 red LEDs. The proliferation of hSCAPs was detected using a CCK-8 assay. The osteogenic differentiation of hSCAPs was evaluated using alkaline phosphatase (ALP) staining, ALP activity assay and Alizarin red quantitative detection. The effect of 5 J/cm2 red LEDs on the expression levels of the ALP, Runx2, OCN, OPN and BSP genes and proteins was detected by RT-PCR and western blot, respectively. Results: Red LEDs at 1, 3, 5, and 7 J/cm2 promoted the proliferation of hSCAPs (P < 0.05). The effects of red LEDs with different light energies on the proliferation of hSCAPs were different at different time points (P < 0.05). On the 7th and 14th days after irradiation, red LEDs promoted the osteogenic differentiation of hSCAPs, and the effect of 5 J/cm2 red LEDs was the most obvious under osteogenic induction culture conditions (P<0.05). Red LEDs (5 J/cm2) promoted the expression of the ALP, Runx2, OCN, OPN and BSP genes and proteins (P < 0.05). Conclusion Red LEDs promoted the proliferation and osteogenic differentiation of hSCAPs.

OBJECTIVE: To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. METHODS: Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. RESULTS: Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index ( CONCLUSIONS CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway
Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Fibroblasts ; Mice ; Nephroblastoma Overexpressed Protein

Objective:To observe the clinical efficacy and adverse reactions of rituximab in the treatment of systemic sclerosis (SSc).Methods:Eight SSc patients who received rituximab treatment in the Department of Rheumatology of Shanghai Ruijin Hospital from November 2016 to May 2020 were treated with rituximab at week 0, week 2, week 4, week 24 and week 48. The clinical symptoms and laboratory parameters were evaluated at baseline, week 4, week 24 and week 48 respectively. All data were analyzed by Wilcoxon test.Results:All the patients were diagnosed as diffuse SSc, including seven females and one male, with a median disease course of 2.5 years. At week 0, week 24 and week 48, the modified Rodnon skin scores (MRss) were 16.5 (11.8, 29.5) , 14.5 (9.5, 27) ( Z=0.841) and 10.5 (7, 24.3) ( Z=0.420) respectively, which were significantly improved as compared with the baseline ( P<0.05). The patients' self-scores were 60(50, 77.5), 52.5(41.3, 67.5)( Z=0.113) and 47.5(36.3, 57.5)( Z=0.474) respectively, which were significantly improved at week 24 and week 48, and the High Resolution CT (HRCT) scores at baseline and week 48 were 2.7(1.02, 3.7) and 1.6(0.65, 2.95)( Z=0.964) respectively, significantly improved after treatment ( P<0.05). The pulmonary aterial hypertension (PAH) values were 48(41, 58.5) mmHg and 47(38.5, 57) mmHg ( Z=0.315) respectively. There was no significant difference between the two groups. Clinical observation showed that the condition was improved and no adverse reaction occurred at the same time period. Conclusion:The improvement of skin sclerosis, pulmonary interstitial lesion and pulmonary artery pressure can be observed during the treatment with rituximab, which may be a new choice for the treatment of SSc. There is no serious adverse reaction during the treatment, and the patients are well tolerated and safe.

Objective:Anti-synthase syndrome (ASS) is a rare autoimmune disease. To increase the understanding of the disease and reduce the rate of miss diagnosis.Methods:The clinical data of 8 patients with positive anti-synthase antibody afterprimary Sj?gren's syndrome (pSS) were retrospectively analyzed and descriptive statistical analysis was carried out.Results:The diagnosis of Sjogren's syndrome (SS) was in accordance with the revised European criteriaof SS issued by the US-Europe consensus Group in 2002 or the classification criteria of American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) SS in 2016, and the diagnostic ASS was in accordance with the diagnostic criteria of Conners in 2010 or Solomon in 2011. Eight(100%) patients had a history of interstitial lung disease, and 7 (88%) patients had fever (oral temperature >38.5 ℃). All patients were positive for anti-Ro-52 antibody, 4 patients were positive for anti-PL-7 antibody, 2 patients were positive for anti-EJ antibody, 1 patient was positive for both anti-PL-7 antibody and anti-EJ antibody, and 1 patient was positive for anti-PL-12.Conclusion:pSS patients with severe interstitial lung disease or high fever of unknown causes should be screened for anti-synthase antibodies and the possibility of ASS.

Objective? To explore the current status of nurses' knowledge, attitude and practice in Class Ⅲ Grade A hospitals on early enteral nutrition in critically ill patients. Methods? A total of 114 nurses in a Class Ⅲ Grade A hospital in Beijing were selected by convenience sampling method on March of 2019. Self-designed Nurses' Knowledge, Attitude and Practice Questionnaire on Early Enteral Nutrition in Critically Ill Patients was used to investigate the nurses,and the contents included their general information and their related knowledge, attitude, practice towards the critically ill patient's early enteral nutrition. Results? Nurses scored 5.00-85.00 points on Nurses' Knowledge Questionnaire on Early Enteral Nutrition in Critically Ill Patients, with a median of 35.00 points; Attitude Questionnaire scored 0.00-80.00 points, with a median of 80.00 points;Practice Questionnaire scored(51.49±13.18) points, ranging from 13.33 to 83.33 points; 27.19% of nurses had never received relevant knowledge training. Conclusions? Nurses should have comprehensive knowledge of early enteral nutrition for severely ill patient to enable patients receive more effective enteral nutrition support, pay attention to the clinical application of pyloric retroperitoneal feeding technology, integrate dynamic nutrition screening and intra-abdominal pressure measurement into routine nursing work, and find out the exist problems of early enteral nutrition in severely ill patients in time, improve the quality of holistic nursing, so that severely ill patients can get the most effective enteral nutrition support.