Efficacy and adverse reactions of donepezil:a pharmacogenomic study / 中华老年心脑血管病杂志

Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Therapeutic Effect of Gandou Decoction on Wilson's Disease with Dampness Heat Accumulation Accompanied by Rapid Eye Movement Sleep Behavior Disorder / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease （WD） with dampness heat accumulation accompanied by rapid eye movement （REM） sleep behavior disorder （RBD）. MethodFrom April 2019 to August 2023，62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment，while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment，totaling three courses. The scores of traditional Chinese medicine syndromes，RBD screening questionnaire （RBDSQ） scores，RBD questionnaire-Hong Kong （RBDQ-HK） scores，polysomnography （PSG） parameters，24-hour urine copper （24 h U-Cu） levels，and non-ceruloplasmin-bound copper （NCC） levels between the two groups before and after treatment were compared，and adverse reactions were observed. ResultSixty trial cases were ultimately completed，with 30 cases in each group. Before treatment，there was no statistically significant difference in various indicators between the two groups， and thus they were comparable. Compared with those before treatment，the traditional Chinese medicine syndrome scores，RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced，the 24 h U-Cu levels were significantly increased，and the NCC levels were significantly reduced （P<0.05，P<0.01）. Compared with the control group， the observation group showed better improvement in traditional Chinese medicine syndrome scores， RBDSQ scores， RBDQ-HK scores， and NCC levels （P<0.05，P<0.01）. Compared with those before treatment，the total sleep time （TST），sleep efficiency （SE），sleep/REM latency，the proportion of N1/N2/REM stages，arousal index （ARI），and proportion of phasic electromyographic activity （P-EMG-A） were significantly improved in both groups （P<0.05）. Compared with the control group after treatment，the observation group showed more significant improvements in the proportion of TST，SE，REM stages，ARI，and P-EMG-A proportion （P<0.05）. ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.

Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy / 中华内科杂志

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Relationship between early dialysis anemia status and prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival.Methods:It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality.Results:A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions:The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Short-term efficacy of minimally invasive esophagectomy combined with three-field versus two-field lymphadenectomy for 257 patients / 中国胸心血管外科临床杂志

@#Objective To explore the safety of minimally invasive esophagectomy (MIE) with three-field lymphadenectomy (3-FL) for esophageal squamous cell carcinoma (ESCC) by comparing the short-term outcomes between the 3-FL and the two-field lymphadenectomy (2-FL) in MIE. Methods The clinical data of patients with ESCC who underwent minimally invasive McKeown esophagectomy in our hospital from July 2015 to March 2022 were collected retrospectively. Patients were divided into a 3-FL group and a 2-FL group according to lymph node dissection method. And the clinical outcomes and postoperative complications were compared between the two groups. Results A total of 257 patients with ESCC were included in this study. There were 211 males and 46 females with an average age of 62.2±8.1 years. There were 109 patients in the 3-FL group and 148 patients in the 2-FL group. The operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group (P<0.001). There was no statistical difference between the two groups in the intraoperatve blood loss (P=0.376). More lymph nodes (P<0.001) and also more positive lymph nodes (P=0.003) were obtained in the 3-FL group than in the 2-FL group, and there was a statistical difference in the pathological N stage between the two groups (P<0.001). But there was no statistical difference in the incidence of anastomotic leak (P=0.667), chyle leak (P=0.421), recurrent laryngeal nerve injury (P=0.081), pulmonary complications (P=0.601), pneumonia (P=0.061), cardiac complications (P=0.383), overall complications (P=0.147) or Clavien-Dindo grading (P=0.152) between the two groups. Conclusion MIE 3-FL can improve the efficiency of lymph node dissection and the accuracy of tumor lymph node staging, but it does not increase the postoperative complications, which is worthy of clinical application.

Study on the correlation between color and inner quality during the processing of Prunus mume carbon and its processing end point / 中国药房

OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.

Construction and validation of a simple model for predicting the risk of prenatal depression / 四川精神卫生

BackgroundMental illness during pregnancy has become a major public health problem in China over the recent years， and depression is the most common psychological symptom during pregnancy. Current research efforts are directed towards the therapy on prenatal depression， whereas the construction of prediction model for prenatal depression risk has been little studied. ObjectiveTo construct a simple model for predicting the risk of prenatal depression， thus providing a valuable reference for the prevention of maternal depression during pregnancy. MethodsA total of 803 pregnant women attending three hospitals in Nanchong city were consecutively recruited from May 2021 to February 2022. A self-administered questionnaire was developed for the assessment of social demographic variables， obstetrical and general medical indexes and psychological status of all participants， and Self-rating Depression Scale （SDS） was utilized to screen for the presence of maternal depression. Subjects were randomly assigned into modelling group （n=635） and validation group （n=168） at the ratio of 8∶2 under simple random sampling with replacement. The candidate risk factors of maternal depression during pregnancy were screened using binary Logistic regression analysis， and the predictive model was constructed. Then the performance of the predictive model was validated using receiver operating characteristics （ROC） curve. Results① Lack of companionship （β=-0.692， OR=0.501， 95% CI： 0.289~0.868）， low mood during the last menstrual period （β=-1.510， OR=0.221， 95% CI： 0.074~0.656）， emotional stress during the last menstrual period （β=-1.082， OR=0.339， 95% CI： 0.135~0.853）， unsatisfactory relationship between mother-in-law and daughter-in-law （β=-1.228， OR=0.293， 95% CI： 0.141~0.609）， and indifferent generally relationship between mother-in-law and daughter-in-law （β=-0.831， OR=0.436， 95% CI： 0.260~0.730） were risk factors for prenatal depression in pregnant women （P<0.05 or 0.01）. ② Model for predicting the prenatal depression risk yielded an area under curve （AUC） of 0.698 （95% CI： 0.646~0.749）， the maximum Youden index was 0.357 in modelling group with the sensitivity and specificity was 0.606 and 0.751， and an AUC of 0.672 （95% CI： 0.576~0.767） and maximum Youden index of 0.263 in validation group with the sensitivity and specificity of 0.556 and 0.707. ConclusionThe simple model constructed in this study has good discriminant validity in predicting of the risk of prenatal depression. ［Funded by Nanchong Social Science Research Project of the 14th Five-Year Plan （number， NC21B165）］

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Impact of early serum sodium concentrations on prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To determine the impact of early serum sodium concentrations on the survival prognosis in maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. The newly admitted hemodialysis patients who were included in the registration system of Zhejiang Province Dialysis Quality Control Center from January 1, 2010 to December 31, 2019 were identified. Follow-up was conducted until December 31, 2020. Baseline data were collected for the first three months of dialysis, in which the mean level of serum sodium was defined as early serum sodium. Patients were divided into five groups based on early serum sodium level. Restricted cubic spline (RCS) was used to fit the relationship between long-term serum sodium level and risk of death. Kaplan-Meier model and Log-rank test were used to compare the survival rates of different groups. Multivariable Cox regression was used to analyze the correlation between early serum sodium level and death.Results:A total of 26 309 MHD patients were included in this study, and their ages were (59.07±15.41) years (ranging from 18 to 100 years). Among them, 13 643 (51.9%) were over 60 years old and 15 843 (60.2%) were males. Among the primary diseases of chronic renal failure, chronic glomerulonephritis was the first [13 703 cases (52.1%)], followed by diabetic nephropathy [6 460 cases (24.6%)], hypertensive nephropathy [1 293 cases (4.9%)], polycystic kidney disease [1 164 cases (4.4%)], etc. According to early serum sodium level, 12 883 patients (49.0%) had hyponatremia (serum sodium <135 mmol/L), of which 4 001 patients (15.2%) had serum sodium ≤130 mmol/L; 1 529 patients (5.8%) had hypernatremia (serum sodium >145 mmol/L). Patients were divided into the following 5 groups: 4 001 cases (15.2%) in group 1 (serum sodium ≤130 mmol/L), 8 882 cases (33.8%) in group 2 (130 <serum sodium <135 mmol/L), 8 231 cases (31.3%) in group 3 (135≤serum sodium ≤140 mmol/L), 3 666 cases (13.9%) in group 4 (140 < serum sodium≤145 mmol/L) and 1 529 cases (5.8%) in group 5 (>145 mmol/L). Among them, patients in the Na≤130 mmol/L group had a slightly older age, a higher proportion of diabetes and cardiovascular disease, a lower level of blood uric acid, albumin, hemoglobin, and a higher level of alkaline phosphatase and leukocytes, while patients in the Na >145 mmol/L group had an older age and a higher proportion of cardiovascular disease. After follow-up of (55.67±33.58) months, a total of 4 954 patients (18.8%) died, 1 537 patients (5.8%) underwent kidney transplantation, 128 patients (0.5%) were converted to peritoneal dialysis. Of the deaths, 990 (20.0%) were due to cardiovascular diseases, 498 (10.1%) to cerebrovascular diseases and 400 (8.1%) to infections, and cardiovascular disease was the main cause of death. RCS curve fitting of the relationship between serum sodium level and risk of death found that the all-cause mortality hazard ratio ( HR) increased with decreasing or increasing serum sodium, and the optimal serum sodium was between 135 mmol/L and 140 mmol/L. Kaplan-Meier survival curve showed that the risk of all-cause death (Log-rank test, χ2=66.5, P<0.001), the risk of cardiovascular death (Log-rank test, χ2=31.5, P<0.001) and the risk of infection death (Log-rank test, χ 2=28.6, P<0.001) were significantly different among five groups. The 10-year cumulative survival rate was 63.0%, 71.5%, 72.5%, 67.8% and 61.4% in groups with different serum sodium levels from low to high, and the 10-year cumulative cardiovascular mortality rate was 9.6%, 6.2%, 5.5%, 7.3% and 11.7%, and the 10-year cumulative infection mortality rate was 4.9%, 3.2%, 1.7%, 2.8% and 3.9%. Multivariable Cox regression showed early serum sodium level >145 mmol/L was an independent relevant factor for all-cause death in MHD patients ( HR=1.237, 95% CI 1.045-1.465, P=0.013). Conclusions:MDH patients are more likely to develop hyponatremia in the early stage of dialysis. The cumulative survival rate of all-cause death, cardiovascular death and infection death in patients with predialysis serum sodium ≤130 mmol/L and >145 mmol/L within three months after initiation of dialysis is significantly lower than those in other levels. Early serum sodium >145 mmol/L is associated with higher mortality in MHD patients.

Graft survival rate and its influence on calcium and phosphorus metabolism after total parathyroidectomy and auto-transplantation in patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To investigate the graft survival rate after total parathyroidectomy (TPTX) plus forearm muscle auto-transplantation in patients with secondary hyperparathyroidism (SHPT) and evaluate the effect of graft survival status on calcium and phosphorus metabolism.Methods:It was a retrospective cohort study. The end-stage renal disease patients who were diagnosed with SHPT and underwent TPTX plus forearm muscle auto-transplantation from November 2015 to December 2018 at the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. The clinical data including serum calcium, phosphorus, intact parathyroid hormone and alkaline phosphatase preoperative and postoperative 1 week, 1 month and 6 months, and cumulative requirements of calcium carbonate and calcitriol in postoperative 1 month and 6 months were collected. The graft survival rate was summarized and the differences of serum calcium, phosphorus, and supplementation dosage of calcium and calcitriol after surgery between the graft survival group and the graft non-survival group were compared.Results:A total of 191 patients were included in the study, with 95 males (49.7%), and 172 patients of age <60 years old. There were 154 grafts surviving with a graft survival rate of 80.6%. There were no significant differences in the levels of serum calcium, phosphorus, alkaline phosphatase at 1 week, 1 month and 6 months after surgery, and cumulative dosage of calcium carbonate at 1 month and 6 months after surgery between the two groups (all P>0.05). The dose of calcitriol in the graft non-survival group was significantly higher than that in the graft survival group within 1 month after surgery [41.50 (30.00, 45.00) μg vs. 32.75 (25.50, 40.50) μg, Z=-2.307, P=0.021]. However, there was no significant difference in cumulative calcitriol supplementation between the two groups within 6 months after surgery ( P>0.05). Conclusions:The graft survival rate after TPTX plus forearm muscle auto-transplantation is high in SHPT patients. Within 6 months after surgery, there is no significant difference in serum calcium, phosphorus and cumulative supplemental doses of calcium and calcitriol between the graft survival and non-survival groups.

Association of early serum potassium with all-cause mortality in adult maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To investigate the association of early serum potassium level with all-cause mortality in adult maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. The data of patients newly entered MHD in the registration system of Zhejiang province dialysis quality control center from January 1, 2010 to December 31, 2019 were collected. Follow-up was conducted until December 31, 2020. The average value of predialysis serum potassium within the first 3 months starting hemodialysis was defined as early serum potassium, and patients were divided into 6 groups according to their early serum potassium levels. Death within 1 year of MHD patients was defined as short-term death. Kaplan-Meier method was used to compare the long-term and short-term survival rates of the six groups. Cox regression model was used to analyze the association of different serum potassium levels with the short-term all-cause mortality of adult MHD patients.Results:A total of 27 362 patients aged (61.2±14.4) years old were included, including 16 775 males (61.3%), 1 303 patients (4.8%) with hypokalemia (serum potassium<3.5 mmol/L) and 10 034 patients (36.7%) with hyperkalemia (serum potassium≥5.0 mmol/L). Among them, there were 5 145 patients (18.8%) with serum potassium≥5.5 mmol/L. According to the early serum potassium levels, the patients were divided into group 1 (serum potassium<3.5 mmol/L), group 2 (3.5≤ serum potassium<4.0 mmol/L), group 3 (4.0≤serum potassium<4.5 mmol/L), group 4 (4.5≤serum potassium<5.0 mmol/L), group 5 (5.0≤serum potassium<5.5 mmol/L) and group 6 (serum potassium≥ 5.5 mmol/L), respectively. Until the end of follow-up, the follow-up time was (40.7±27.8) months and 5 400 patients died. Cardiovascular and cerebrovascular diseases [1 551 cases (28.7%)] and infections [366 cases (6.8%)] were the main causes of death. Kaplan-Meier survival analysis showed that the long-term and short-term cumulative survival rates in the serum potassium<3.5 mmol/L group were the lowest among the 6 groups (Log-rank test, χ2=119.0, P<0.001; χ2=74.6, P<0.001, respectively). Multivariate Cox regression analysis showed that early serum potassium<3.5 mmol/L was an independent influencing factor for short-term all-cause death in MHD patients (with 4.5≤serum potassium<5.0 mmol/L as reference, HR=1.54, 95% CI 1.26-1.89, P<0.001). In the subgroup of age≥65 years, multivariate Cox regression model showed that serum potassium<4.5 mmol/L was independently associated with short-term death in MHD patients (with 4.5≤ serum potassium< 5.0 mmol/L as reference, serum potassium<3.5 mmol/L, HR=2.16, 95% CI 1.69-2.75, P<0.001; 3.5≤serum potassium<4.0 mmol/L, HR=1.40, 95% CI 1.14-1.72, P=0.001; 4.0≤serum potassium< 4.5 mmol/L, HR=1.46, 95% CI 1.21-1.75, P<0.001), while in the subgroup of age<65 years, serum potassium level was not significantly associated with short-term mortality risk in MHD patients. The early serum potassium level was associated with the risk of short-term all-cause death in a "U" shape, and both low and high potassium levels increased the risk of short-term all-cause death. The optimal early blood potassium level was about 4.75 mmol/L. Conclusions:The prevalence of hypokalemia at early stage of dialysis in adult MHD patients is about 4.8%. There is a U-shaped association between early serum potassium level and short-term (1 year) all-cause mortality risk, and early serum potassium<3.5 mmol/L is an independent risk factor for long-term and short-term all-cause mortality in MHD patients.

Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress / 国际口腔科学杂志·英文版

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a / 生物工程学报

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.

Thermosensitive chitosan-collagen composite hydrogel loaded with basic fibroblast growth factor retards ventricular remodeling after myocardial infarction in mice / 中国组织工程研究

BACKGROUND: Chitosan or collagen alone can improve the microvessel density in myocardial infarction area and participate in the short-term myocardial repair after myocardial infarction. Based on this research group, thermosensitive chitosan-collagen composite hydrogel was prepared, which confirmed that it had good physical and chemical properties and was suitable for myocardial tissue engineering scaffold materials. OBJECTIVE: To prepare the chitosan-collagen composite hydrogel loaded with basic fibroblast growth factor, and to analyze its physical and chemical properties, biocompatibility and prognosis in vivo after treatment of myocardial infarction in mice. METHODS: (1) Basic fibroblast growth factor was loaded in chitosan-collagen composite hydrogel and chitosan hydrogel separately, and the release efficiency of basic fibroblast growth factor in hydrogels was detected. (2) H9C2 cardiomyocytes were seeded in two hydrogels loaded with basic fibroblast growth factor, and cell proliferation was detected by CCK8 assay. (3) C57BL/6J mice model of myocardial infarction was established and randomly divided into three groups. The blank group was injected PBS into the myocardial infarction area. The control group was injected with chitosan hydrogel loaded with basic fibroblast growth factor. The experimental group was injected with chitosan-collagen composite hydrogel loaded with basic fibroblast growth factor. Echocardiography and myocardial histology were performed 28 days after operation. The experiment was approved by Ethics Committee of Shanxi Medical University. RESULTS AND CONCLUSION: (1) Compared with chitosan hydrogel, chitosan-collagen composite hydrogel could promote the release of basic fibroblast growth factor in gel. (2) Compared with the chitosan hydrogel loaded with basic fibroblast growth factor, the chitosan-collagen composite hydrogel loaded with basic fibroblast growth factor could promote the proliferation of cardiomyocytes. (3) Echocardiography showed that the left ventricular ejection fraction and the shortening rate of left ventricular short axis in the experimental group and the control group were higher than those in the blank group (P < 0.05). Left ventricular ejection fraction and the shortening rate of left ventricular short axis in the experimental group were higher than those in the control group (P < 0.05). (4) The myocardial histological observation showed that the infarct area of the experimental group and the control group was smaller than that of the blank group (P < 0.05). The infarct area wall thickness of the experimental group and the control group was larger than that of the blank group (P < 0.05). The infarct area of the experimental group was smaller than that of the control group (P < 0.05), and the infarct area wall thickness of the experimental group was larger than that of the control group (P < 0.05). (5) The results showed that the chitosan-collagen composite hydrogel loaded with basic fibroblast growth factor had good biocompatibility, and animal transplantation could significantly reduce the ventricular remodeling after myocardial infarction.

Effects of pharmaceutical excipients on CYP3A activity and its guiding effects on quality and efficacy consistency evaluation of generic drugs / 中国临床药理学与治疗学

The prescription and technology of pharmaceutical preparations are the basis for ensuring the quality and efficacy of medicines. Pharmaceutical excipients are important part of pharmaceutical preparations. As it's known to all that some pharmaceutical excipients can affect the activity of CYP3A, and then may influence the metabolism and bioavailability of its substrates in vivo. Relative bioavailability is a key element of generic drug research in China and the United States. Our country is advancing the quality and efficacy consistency evaluation of generic drugs. Therefore, it is of great practical significance to understand the impact of pharmaceutical excipients on CYP3A and its guiding role in consistency evaluation.

Changes of cardiac function in rats with myocardial infarction after umbilical cord-derived mesenchymal stem cell transplantation: A meta-analysis / 中国组织工程研究

BACKGROUND: It has been shown that compared with stem cells from other sources, umbilical cord-derived mesenchymal stem cells have lower immunogenicity, and their application has significant effect in rats with myocardial infarction. OBJECTIVE: To systematically evaluate the effects of umbilical cord-derived mesenchymal stem cells on cardiac function of rats with myocardial infarction. METHODS: PubMed, Cochrane, Embase, CBM, CNKI, WanFang, VIP and CJD databases were retrieved for the literature concerning umbilical cord-derived mesenchymal stem cells for treating rats with myocardial infarction published before June 2019. Two researchers independently completed literature screening, data extraction and methodological quality evaluation according to the inclusion criteria. Meta-analysis was conducted on Stata 14.0. RESULTS AND CONCLUSION: A total of 9 articles were included, involving 216 rats. Meta-analysis showed that: (1) Umbilical cord-derived mesenchymal stem cells significantly increased the left ventricular ejection fraction after myocardial infarction in rats [95% confidence interval (CI) (3.16, 3.76), P < 0.001]. (2) Umbilical cord-derived mesenchymal stem cells significantly increased the left ventricular short axis shortening rate after myocardial infarction in rats [95%CI (0.18, 0.54), P < 0.001]. (3) Umbilical cord-derived mesenchymal stem cells significantly shortened the left ventricular end-diastolic internal diameter [95%CI (-1.90,-0.99), P=0.042] and left ventricular end-systolic internal diameter [95%CI (-6.56,-4.65), P < 0.001]. (4) Umbilical cord-derived mesenchymal stem cells significantly improved the left ventricular end-diastolic volume [95%CI (-2.01,-1.11), P < 0.001] and left ventricular end-systolic volume [95%CI (-3.44,-2.17), P < 0.001]. In summary, umbilical cord-derived mesenchymal stem cell transplantation is effective and safe in the treatment of myocardial infarction in rats. Due to the limitation of the quality of the included literature, the above conclusions need to be validated by high-quality and large-sample randomized controlled trials.

Clinicopathological analysis of immunoglobulin G4-related diseases with interstitial nephritis / 中华风湿病学杂志

Objective To analyze the clinicopathological features and prognosis of immunoglobulin G (IgG)4-related diseases with interstitial nephritis. Methods Forty cases of IgG4-related diseases diagnosed by pathology in our hospital from 2014 to 2018 were collected and their clinicopathological features were analyzed. Four patients with IgG4-related disease with interstitial nephritis were analyzed, including clinical laboratory tests and histopathological features, and immunohistochemical analysis of the type and proportion of renal interstitial infiltrating cells. At the same time, the treatment and prognosis of the patients were analyzed. Results Among 40 cases of IgG4-related diseases, 11 cases had parotid submandibular gland involvement (accounted for 28％), labial gland involvement (7 cases, 18％) and lymph node enlargement (6 cases, 15％). Patients with kidney involvement (4 cases, 10％) all presented with IgG4-related tubulo-interstitial nephritis (IgG4-TIN). All of them were elderly males, and 2 had glomerulopathy. One of them had anti-neutrophil cytoplasmic antibodies (ANCA)-related vasculitis renal damage. The number of CD4-positive cells in renal interstitium was more than CD8-positive cells. Another case complicated with IgA nephropathy. Renal dysfunction occurred in all 4 cases, and serum IgG4 level ranged from 4.65 g/L to 23.8 g/L. All 4 patients received glucocorticosteroid and symptomatic treatment, and the prognosis was good. Conclusion IgG4-related diseases may involve mul-tiple organs, renal dysfunction may occur when the kidney is involved. Interstitial nephritis is the major clinical manifestation. Glomerular lesions may accelerate the progress of IgG4-TIN. Corticosteroid therapy is effective.

Osteogenic potential of the Schneiderian membrane and its factors / 中华口腔医学杂志

Insufficient bone quantity in the posterior region of the maxilla is one of the difficulties for dental implant placement. Maxillary sinus augmentation is considered to be a reliable treatment to solve the problem of insufficient bone quantity. With the increase of researches on maxillary sinus elevation, the debate over osteogenesis potential of Schneiderian membrane is getting more attention. Therefore, this article will review the current research on osteogenic potential of the Schneiderian membrane and its influence factors.

Investigaion on influencing factors and maternal awareness and knowledge of obstructive sleep apnea syndrome / 中华围产医学杂志

Objective To investigate maternal awareness and knowledge of obstructive sleep apnea syndrome (OSAS) and their compliance with polysomnography monitoring in snoring gravidas.Methods This study enrolled 589 volunteered gravidas who were treated at the 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force or Maternal and Child Health Hospital of Jiangxi Province from April 2016 to April 2017.The maternal knowledge of OSAS (0 point:complete lack of knowledge of OSAS;1 to 4 points:with partial knowledge of OSAS;5 points:correct understanding of OSAS) and the way of obtaining this knowledge were studied using a self-designed questionnaire.Influencing factors,including gestational weeks,educational background,snoring and high-risk pregnancy,were also analyzed.Chi-square test was used for statistical analysis.Results The 589 gravidas had few knowledge of OSAS and only 11 of them [1.9％ (11/589)] were able to fully understand OSAS (5 points).The proportion of women who were completely lack the knowledge of OSAS (0 point) in those less-educated women was higher than in those well-educated group [61.9％ (78/126) vs 52.0％ (241/463),x2=3.873,P=0.049].Among the gravidas who were unaware of their snoring condition,those completely lack the knowledge of OSAS (0 point) accounted for 67.0％ (209/312),which was higher than the percentage among gravidas knowing they had or did not have snoring problem [35.6％ (21/59),40.8％ (89/218);x2=20.755,35.687;both P＜0.017].There was no significant difference in OSAS awareness among gravidas regardless of their gestations and whether they were classified as high-risk or not (all P＞0.05).Of 59 gravidas with snoring,only 15 (25.4％) accepted polysomnography monitoring.Eight out of the 589 gravidas (1.4％) were diagnosed with OSAS during pregnancy.Conclusions Gravidas have poor knowledge and awareness of OSAS,especially those with low educational background and not knowing their snoring condition,resulting in poor compliance with polysornnography monitoring and low diagnostic rate of OSAS during pregnancy.

An assessment of color effect on minimal and no-preparation veneers / 实用口腔医学杂志

Objective: To evaluate the color effect of esthetic rehabilitation of anterior teeth restored with the minimal and no-preparation veneers and to analyze the influence factors of satisfaction. Methods: 30 patients were divided into group A (9 patients with tetracycline discoloured teeth treated with 72 veneers) and group B (21 patients with non-tetracycline teeth treated with 66 veneers) . All the selected teeth were restored with the minimal and non-preparation veneers. Before the teeth were prepared and after veneers were cemented, Olympus Crystaleye was employed to obtain L*, a*, b*values of each tooth. The shade was selected according to the patients' expectation and dentist's advice. The color difference (ΔE) before and after restoration of group A and group B, the color difference (ΔE1) between the tooth color after restoration and the expectation color of the patients, the relationship of the satisfaction degree and the color difference (ΔE1), the lightness difference (ΔL*), Δa*and Δb*were analyzed by SPSS 20. 0. Results: After cemented, the color of teeth-veneer-complex obviously improved in both groups. The color difference (ΔE1) between the tooth color before and after restoration, and the expected color between the 2 group was significant (P ＜ 0. 05) . ΔE1, ΔL*, Δa*had great influence on the satisfaction of dentists and patients (P ＜ 0. 05) . Conclusion: The appearance of non-tetracycline teeth restored with the minimal and no-preparation veneers was excellent. The more of the color of the teeth-veneer-complex matched the expectation color, the higher the patients are satisfied with the restorations. The less of the lightness difference, the higher the patients are satisfied with the restorations.