AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective:To analyze the correlation between body mass index (BMI) and the graded expression, subcutaneous depth, and diameter of elbow veins (cephalic vein, median vein, basilic vein) in patients with metabolic syndrome, to provide a method and theoretical basis for precise puncture of peripheral veins in obese patients.Methods:From January to October 2021, a total of 767 patients with metabolic syndrome with gastric volume reduction were selected as the study subjects by retrospective cohort study from the first Affiliated Hospital of Nanjing Medical University. According to the quartile Q1, M and Q3 of BMI level, they were divided into four groups: group A, group B, group C and group D. The subcutaneous depth and diameter of the cephalic vein, median vein and basilic vein were measured by B-ultrasound, and the three veins were evaluated and graded according to the grading criteria of superficial veins.The correlation between BMI and the subcutaneous depth and diameter of the three elbow veins was analyzed, and collected data such as puncture method and puncture times. Results:There was no significant correlation between BMI and subcutaneous depth and vessel diameter of the basilic vein ( r = 0.041 and 0.046, both P>0.05), the level of BMI was positively correlated with the subcutaneous depth and diameter of cephalic vein ( r = 0.275 and 0.117, both P<0.05) and median vein ( r = 0.236 and 0.148, both P<0.05), and a linear regression relationship was found ( OR values were 1.013-1.031, all P<0.05). 187 cases had direct puncture conditions under direct vision, and the success rate of one puncture was 86.63%(162/187).Venipuncture was completed under the guidance of B-mode ultrasound for 25 cases with failure under direct vision and 580 cases without direct puncture conditions under direct vision, the success rate of one puncture was 98.51% (596/605). Conclusions:With the increase of BMI level in patients with metabolic syndrome, the depth and diameter of both cephalic vein and median vein increase, venous exposure is difficult to express. The visual vein puncture guided by B-ultrasound is more accurate and catheterization is more reliable.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Tumor microenvironment (TME) is composed of endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), extracellular matrix (ECM) and other components of the complex biological environment. TME interacts with the tumor cells through a large amount of signaling pathways, participates in the process of tumor progression, invasion, and metastasis. Hence, TME has become a potential therapeutic target for cancer treatment, exhibiting excellent therapeutic potential and research value in the field of cancer treatment. Currently, the novel nanotechnology has been widely applied in anticancer therapy, and nanotechnology-mediated drug delivery system is being explored to apply in TME modulation to inhibit tumor progression. Nanotechnology-mediated drug delivery has many advantages over traditional therapeutic modalities, including longer circulation times, improved bioavailability, and reduced toxicity. This review summarized the research of targeted nano-drug delivery based on TME regulation, including regulation strategies based on CSCs, CAFs, immune cells, ECM, tumor vascularization, exosomes, and microbiota. In addition, we summarized the advantages, opportunities, and challenges of TME regulation strategy compared with traditional treatment strategy, which provides a reference for the application of nano-drug delivery system based on TME regulation strategy in tumor precision therapy.

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.
Male ; Female ; Humans ; Pancreatic Fistula/surgery* ; Retrospective Studies ; Blood Loss, Surgical ; Pancreatectomy/methods* ; Pancreaticoduodenectomy ; Postoperative Complications ; Surgeons ; Postoperative Hemorrhage ; Pancreatic Neoplasms/surgery*

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m² referred to obese individuals, 25≤BMI < 30 kg/m² referred to overweight individuals, 18.5≤BMI < 25 kg/m² referred to normal individuals, BMI < 18.5 kg/m² referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m².Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m², 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m², amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m², 24.7%) and 22 obese individuals (BMI≥30 kg/m², 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.
Humans ; Body Mass Index ; Overweight/epidemiology* ; Retrospective Studies ; Arthritis, Rheumatoid/epidemiology* ; Obesity/epidemiology* ; Diabetes Mellitus ; Hypertension/complications* ; Fatty Liver/complications* ; Hyperlipidemias/complications* ; Osteoporosis/complications* ; Anemia

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (1324 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 1324 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13P=0.002). The incidence of MACCE in 1324 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.
Aged ; Coronary Artery Disease/surgery* ; Diabetes Mellitus ; Drug Therapy, Combination ; Drug-Eluting Stents/adverse effects* ; Female ; Hemorrhage ; Humans ; Male ; Myocardial Infarction/epidemiology* ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prognosis ; Prospective Studies ; Stroke ; Treatment Outcome

OBJECTIVE: To analyze health related quality of life (HR-QoL) and physical function of outpatient department patients with rheumatoid arthritis (RA), and to analyze disease activity influence in HR-QoL and functional capacity as well as the divergences between different disease activity standards. METHODS: The demographic and clinical data of 207 RA cases from Department of Rheumatology and Immunology, Peking University Third Hospital from Jan 2021 to Jul 2021 were collected. RA-specific quality of life (RA-QoL) and the medical outcome 36-item short form health survey (SF-36)were collected to estimate the quality of life. The t test was used for the quantitative data in accordance with normal distribution. RESULTS: A total of 207 cases were included, with RA-QoL score of 7.8±7.1, physical component summary (PCS) score of 63.8±23.8, and mental component summary (MCS) score of 71.7±21.0. According to disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), there were 119 patients (59.5%) with remission and low disease activity, and 125 patients (62.5%) with simplified disease activity index (SDAI). The HR-QoL of the patients with remission or low disease activity was significantly better than that of the patients with moderate or high disease activity. The physical function (76.7±17.2 vs. 86.4±15.0, t=2.855, P < 0.01), bodily pain (67.8±8.5 vs. 77.7±15.6, t=4.277, P < 0.01) and health transition (52.8±22.3 vs. 63.9±24.1, t=2.134, P < 0.05) in the low disease activity (LDA) group were lower than those in the complete remission (REM) group according to DAS28-ESR. Other domains of SF-36 and RA-QoL had no differences between these two groups. PCS in the LDA group was lower than that in the REM group (68.3±15.2 vs. 77.3±15.2, t=2.716, P < 0.01), but MCS was not different between the two groups. Determined by SDAI, the RA-QoL score in the LDA group was significantly higher than that in the REM group (9.4±7.1 vs. 6.0±4.8, t=-2.260, P < 0.05), the various dimensions of physical function in the SF-36 score and the PCS score (69.9±16.4 vs. 81.4±15.1, t=3.879, P < 0.05) were lower than that in the REM group, and the MCS score was lower than that in the REM group (67.9±19.3 vs. 74.5±18.8, t=2.721, P < 0.01). CONCLUSION The RA-QoL and SF-36 scores of RA patients in outpatient clinics were better, and the MCS was higher than the PCS. Treat-to-target is essential to improve HR-QoL. SDAI can better indicate the HR-QoL of each domain in REM and LDA RA patients.
Humans ; Quality of Life ; Cross-Sectional Studies ; Severity of Illness Index ; Arthritis, Rheumatoid ; Remission Induction

Objective:To study the coronal bone structure matching of distal radius in normal population and some patients with postoperative distal radius fracture, and to explore the clinical significance of coronal bone structure reduction of distal radius fracture.Methods:CT scans of 80 asymptomatic wrists were performed. Mimics 20.0 and 3-Matic research software were used to measure the matching data of coronal bone structure of the distal radius. Total of 44 patients with distal radius fractures treated with open reduction and volar plate fixation were collected. According to the data coronal bone structure of the distal radius, the matching group was in the normal range, and the mismatching group was less than the normal range. X-ray films were used to evaluate fracture healing, humeral height, ulnar angle and palm tilt angle at 3 months and 12 months after operation. The clinical indexes of wrist pain, wrist function, grip strength and activity were recorded in 2 groups. The DASH score was used for evaluation, and statistical comparisons was made between the two groups of related indicators.Results:The coronal bone structure matching value of the distal radius in 80 normal adults was 45.0%±16.2%. All the 44 patients with distal radius fracture were followed up for an average of 16 months. The postoperative wound healing was good, and the bone healing standard was reached 3 months after the operation. 3 months after surgery, radius height, ulnar deviation angle and palmar inclination angle of the mismatched group were all smaller than those of the matched group, but the differences had no statistical significance. The pronation angle in the mismatched group (68.82°±11.62°) was lower than that in the matched group (76.91°±9.14°), and the difference was statistically significant ( t=2.567, P=0.014). The DASH score in the mismatched group (15.53±2.36) was higher than that in the matched group (13.62±2.52), and the difference was statistically significant ( t=2.591, P=0.013). 12 months after surgery, the VAS score of the matched group (2.08±2.95) was less than that of the mismatched group (2.95±1.24), and the difference was statistically significant ( t=2.348, P=0.024). There was no significant difference in wrist range of motion, grip strength and DASH score between the two groups. Conclusion:The coronal bone structure matching of distal radius is about 45.0% in normal population. Early wrist dysfunction, limited pronation, and wrist pain may occur when the postoperative matching degree of the distal radius fracture is not within the normal range.

Background: Metabolic diseases pose considerable burden on the healthcare system worldwide, indi-cating the significance of prevention and treatment. In constitution theory of traditional Chinese med-icine, phlegm-dampness constitution (PDC) is the common basis of metabolic diseases. In clinical practice, Huatan Qushi (HTQS) decoction targeting on PDC can effectively improve metabolic indicators. However, its underlying biochemical mechanism still remains unclear.Methods: Eight PDC participants received HTQS decoction for three months. Their blood was collected at baseline and 1 and 3 months after intervention started. Related biomedical indicators were detected. High-throughput sequencing and RT-qPCR were used for validation. Due to the missing data, repeated measures with missing values in mixed models were used. Results: After 3-month treatment, HDL-C level increased (P<.001) and FBG, FINS, and HbA1c all showed decreasing trend at different time points (all P < .05). After miRNA high-throughput sequencing, compared with the baseline, differential miRNAs at 1 and 3 months were screened, and target gene prediction and KEGG pathway enrichment analysis were performed. The results displayed that metabolic disease-related pathways mainly included pathways in cancer, PI3K-Akt signaling pathway, etc. Further, RT-qPCR showed that hsa-miR-1237-3p differed statistically (P =.008). Then we validated the target genes of hsa-miR-1237-3p in the"Pathways in Cancer"pathway including SDF1, AC, CRK, and HGF, also known as upstream target genes of PI3K/AKT pathway. The results showed that two indicators of CRK and HGF were in statistical significance (P=.045 and P=.036, respectively). Conclusion: PDC serves as a common basis for various metabolic diseases. Through adjusting PDC, HTQS decoction can improve biomedical indicators including blood glucose, HbA1c, insulin, and HDL-C. The target pathway is"Pathways in cancer". Specifically, HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237-3p, and probably exerts effects on their downstream PI3K/AKT pathway.