Correlation of mitochondrial tRNA variants with coronary heart disease in a Chinese pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms.@*METHODS@#A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level.@*RESULTS@#This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively.@*CONCLUSION@#Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.

Intervention research status of traditional Chinese medicine monomers on autoimmune diseases by regulating Th17/Treg axis based on gut microbiota / 中国药房

Autoimmune diseases（ADs） are diseases in which the body’s immune tolerance is impaired， causing damage to its tissues. The pro-inflammatory helper T cell 17 （Th17） and anti-inflammatory regulatory T cell （Treg） are functionally antagonistic to each other， and the immune imbalance between them and the imbalance of related inflammatory factors are closely related to the occurrence of a variety of ADs. Plenty of evidence has shown that gut microbiota can regulate Th17/Treg differentiation， rebuild immune tolerance and delay the ADs process through regulating cytokine production， transcription factor expression and energy metabolism. This paper reviews the intervention effects of traditional Chinese medicine（TCM） monomers on the common ADs by regulating Th17/Treg differentiation balance based on intestinal flora： ulcerative colitis，rheumatoid arthritis and diabetes mellitus type 1. It is found that its mechanism of action may be to restore the balance of pro-inflammatory factors and anti-inflammatory factors to alleviate intestinal mucosal barrier damage， reduce synovial angiogenesis and improve pancreatic β cell destruction， which provides some ideas for the prevention and treatment of ADs with integrated traditional Chinese and western medicine.

A diagnostic and predictive model for vascular cognitive impairment in elderly patients with acute partial anterior circulation infarction / 中华老年医学杂志

Objective:To investigate risk factors for vascular cognitive impairment(VCI)in elderly patients 12-18 months after the onset of acute partial anterior circulation infarction(PACI), and to establish a diagnostic and predictive model.Methods:This was a prospective study. Demographic characteristics, vascular risk factors and laboratory data of 148 patients with acute PACI were collected, and patients were followed up for 12-18 months.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate patients' cognitive function.Logistic stepwise regression was used to screen risk factors for VCI.We established a diagnostic and predictive model.The area under the receiver operating(ROC)curve(AUC)was used to evaluate the efficiency of the model.Results:A total of 126 subjects completed the 12-18 month follow-up.Multivariate logistic regression analysis found that high homocysteine(Hcy)( OR=1.082, 95% CI: 1.002-1.167), high glycated hemoglobin(HbA1c)( OR=1.653, 95% CI: 1.052-2.598), high National Institutes of Health Stroke Scale(NIHSS)score( OR=1.291, 95% CI: 1.098-1.518), high hypersensitive C-reactive protein(hs-CRP)( OR=1.026, 95% CI: 1.005-1.047)and low education level( OR=2.485, 95% CI: 1.231-5.018)were independent risk factors for VCI in patients 12-18 months after PACI( P<0.05). The AUC of the diagnostic and predictive model was 0.828(95% CI: 0.755-0.902). Conclusions:High Hcy, NIHSS score, hs-CRP and low education level are independent risk factors for VCI in patients 12-18 months after PACI.The diagnostic and predictive model can help to screen patients at high-risk for VCI, so that timely clinical recognition, diagnosis and treatment can be made after acute PACI.

Analysis on research evolution, status and hotspot of hospital Party construction work based on CNKI database / 中华医院管理杂志

Objective:To identify current research hotspot and future trends of hospital Party construction work from 2009 to 2019, provide references for promoting integration of Party construction with medical work to guide the development of the hospital.Methods:Literature published during 2009-2019 were retrieved in CNKI database using the method of subject research. The Citespace V software was used to generate the research institutions and cooperative network, the keyword co-occurrence network and emergent word graph, information visualization was used to analyze the research institutions, research hotspots, research trends and frontiers.Results:A total of 1 161 papers were obtained. The cooperation between research institutions and hospitals needed to be strengthened. In the past 10 years, the researches focused on the management of Party members and the standardization construction of Party branches, the empirical research combining the policy hotspots, and the promotion of development of hospitals by Party construction.Conclusions:The cooperative research mode between hospitals and universities should be carried out. The internal integrity of the theoretical system needs reinforcement, and the achievement transformation of Party construction research also should be enhanced.

Prognostic factors of lymph node-negative metastasis gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors of patients with lymph node-negative metastasis gastric cancer (pN0).</p><p><b>METHODS</b>Clinicopathological data of patients with pN0 gastric cancer who underwent radical operation at the Department of Surgical Oncology, The First Hospital of China Medical University from May 1980 to August 2012 were collected and analyzed retrospectively.</p><p><b>INCLUSION CRITERIA</b>(1) Patients were diagnosed as gastric adenocarcinoma; (2) Postoperative pathology confirmed T1a to 4bN0M0 gastric cancer; (3) Total number of harvested lymph node was more than 15. The patients, who died within 1 month after the operation, died of other diseases, had remnant gastric cancer, or had incomplete follow-up data, were excluded. Univariate analysis was used to analyze the clinical factors that may influence the prognosis of patients with stage pN0 gastric cancer, then, those significant variables were entered into the Cox's proportional hazards regression model for multivariate analysis to obtain the independent prognostic factors for patients with pN0 gastric cancer finally. Furthermore, the prognosis of patients with pN0 advanced gastric cancer (invasive depth ≥ T2) were analyzed using the same method.</p><p><b>RESULTS</b>A total of 610 patients with pN0 gastric cancer were enrolled in the study, including 441 males and 169 females with age ranging from 19 to 83 (mean 56.4±11.0) years, D1 lymph node dissection in 45 cases, D2 lymph node dissection in 543 cases, D3 lymph node dissection in 22 cases, and 384 cases of advanced gastric cancer. The overall followed-up was 1 to 372 (median 32) months. Ninety cases (14.8%) were dead during the follow-up. The median survival was 277.7(95%CI: 257.6 to 297.8) months, and the 1-, 3-, 5-year survival rates were 96.5%, 87%, 83.2%. Univariate analysis showed that tumor diameter, depth of invasion, gross type, lymph node dissection and lymph vessel cancer embolus were related to the prognosis (all P<0.05). The 5-year survival rate of patients with tumor diameter >4 cm was significantly lower than those with tumor diameter ≤4 cm (75.6% vs. 87.8%, P=0.000). The 5-year survival rates of T1a, T1b, T2, T3 and T4 were 98.4%, 92.8%, 84.2%, 61.0% and 31.4% respectively, and the difference was statistically significant (P=0.000). In gross type, 5-year survival rate of early gastric cancer was 96.0%, and of Borrmann I( to IIII( type gastric cancer was 100%, 83.4%, 73.7% and 68.9% respectively, whose difference was statistically significant(P=0.000). The 5-year survival rates in patients undergoing lymph node dissection D1, D2 and D3 were 100%, 83.3% and 58.7%, and the difference was significant (P=0.005). The 5-year survival rate of patients with positive lymphatic cancer embolus was lower than those with negative ones (69.4% vs. 86.9%, P=0.000). Multivariate analysis showed that the gross type [Borrmann II(/early gastric cancer: HR(95% CI)=15.129(3.284 to 69.699), Borrmann III(/early gastric cancer: HR(95% CI)=14.613 (3.292 to 64.875), Borrmann IIII(/early gastric cancer: HR (95% CI)=15.430 (2.778 to 85.718),Borrmann IIIII(/early gastric cancer: HR(95%CI)=12.604 (1.055 to 150.642), P=0.025] and the positive lymphatic cancer embolus [HR(95% CI)=3.241 (2.056 to 5.108), P=0.000] were the independent prognostic factors of patients with pN0 gastric cancer. For pN0 patients with advanced gastric cancer, multivariate analysis showed that the depth of invasion [stage T3/stage T2: HR(95%CI)=1.520 (0.888 to 2.601), stage T4/stage T2: HR(95%CI)=2.235(1.227 to 4.070); P=0.031] and the positive lymphatic cancer embolus [HR(95%CI)=3.065 (1.930 to 4.868); P=0.000] were the independent risk factors influencing the prognosis.</p><p><b>CONCLUSIONS</b>Positive lymphatic cancer embolus and worse gross pattern indicate poorer prognosis of patients with pN0 gastric cancer, which may be used as effective markers in evaluating the prognosis. As for pN0 advanced gastric cancer, invasion depth and positive lymphatic cancer embolus can play a more important role in the prediction.</p>

Rationality of N3 classification and its sub-classification in TNM classification system for advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the rationality of N3 classification and its sub-classification in the 7th UICC/AJCC TNM classification system.</p><p><b>METHODS</b>Clinicopathological data of 610 patients with stage N3 advanced gastric cancer who underwent standard D2 and D2+ radical surgery at the Department of Surgical Oncology, The First Hospital of China Medical University, from January 1980 to March 2010 were analyzed retrospectively. Patients were divided into N3a and N3b groups, and clinicopathological characteristics and prognosis were compared between N3a and N3b patients. Overall survival rate was determined using the Kaplan-Meier estimator. The log-rank test was used to identify differences between the survival curves of different groups. In multivariate analysis, Cox proportional hazard model was used to identify independent factors associated with prognosis.</p><p><b>RESULTS</b>Among 610 patients, 426 were men and 184 were women, 394 were N3a and 216 were N3b, with a mean age of(57±11) years old (range 23 to 83). A total of 19 842 lymph nodes were examined, in which 9 575 nodes were positive, with the metastatic ratio of 48.3%. The 5-year overall survival rate was 20.0%. Univariate analysis of prognostic factors suggested that tumor location (P=0.000), tumor size (P=0.003), Borrmann type (P=0.000), pathologic type (P=0.043), lymphatic vessel invasion (P=0.000), growth pattern (P=0.019), invasion depth (P=0.000), resection extent (P=0.000) and N3 sub-classification (P=0.000) were significantly associated with the prognosis of N3 patients. Further analysis showed that tumor size (P=0.028), invasion depth (P=0.000) and gastric resection extent (P=0.002) were significantly associated with the prognosis of N3a patients, while Borrmann type (P=0.034), lymphatic vessel invasion (P=0.002), invasion depth (P=0.008) and resection extent (P=0.003) were significantly associated with the prognosis of N3b patients. Multivariate analysis revealed that lymphatic vessel invasion (P=0.009), resection extent (P=0.001), invasion depth (P=0.000) and N3 sub-classification (P=0.000) were independent prognostic factors of N3 patients; resection extent (P=0.004) and invasion depth (P=0.001) were independent prognostic factors of N3a patients; lymphatic vessel invasion (P=0.006) and invasion depth (P=0.009) were independent prognostic factors of N3b patients. Comparison of 5-year survival rate revealed that there was significant difference between T2-4N3a and T2-4N3b patients (P=0.000), while there was no significant difference between T2N3a and T2N3b patients (P=0.140). On the contrary, there were significant differences between T3N3a and T3N3b patients, T4aN3a and T4aN3b patients, T4bN3a and T4bN3b patients, respectively (all P<0.05). Further comparison demonstrated that there were significant differences between T4aN3a and T4bN3a patients, T4aN3b and T4bN3b patients, respectively (P=0.000, P=0.041). Besides, there were no significant differences in 5-year survival rate between T2N3 (at present, staged as III(A), T3N3a (III(B) and T4aN3a (III(C) patients(P=0.506), and T3N3b (III(B), T4aN3b (III(C) and T4bN3a (III(C) patients(P=0.283), respectively.</p><p><b>CONCLUSIONS</b>N3 sub-classification should be included in the final TNM classification system. It is suggested that T2N3, T3N3a and T4aN3a may be categorized into III(A stage, T3N3b, T4aN3b and T4bN3a may be categorized into III(B stage,T4bN3b may be categorized into III(C stage or IIII( stage.</p>

Clinical features and proportion analysis of adult hip fractures at 11 hospitals in Southwest China from 2010 to 2011 / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinical feature and constituent ratio of adult hip fractures in Southwest China.</p><p><b>METHODS</b>The data of adult inpatients and outpatients with hip fractures treated between January 2010 and December 2011 in 11 hospitals of the Southwest China were collected and analyzed. The data includes gender, age, age distribution and fracture pattern according to AO classification.</p><p><b>RESULTS</b>There were a total of 2,833 adult hip fractures, including 1,340 (47.30%) males and 1,493 (52.70%) females, with a male-to-female incidence ratio of 1: 1.11 and a mean age of (66±18) years. The highest frequency of hip fractures was seen in the 71 to 85 years age group (42.18%, 1,195/2,833). There were 844 fractures (29.79%) in the young and middle-aged group (16-<60 years) and 1 898 fractures (70.21%) in the geriatric group (≥60 years). Men had a higher rate than women (men: 577 fractures, 68.4%) in the young and middle-aged group, while women had a higher rate than men (women: 1,226 fractures, 61.64%) in the geriatric group, with a significant difference in the sex distribution between the two groups (χ2=214.001, P<0.01). The proportion of intertrochanteric fracture (type 31-A), femoral neck (type 31-B) and femoral head fracture (type 31-C) was 46.59%, 49.74% and 3.67% respectively. The highest frequency of the sub-type in each fracture type was type 31-A2, type 31-B2 and type 31-C2.</p><p><b>CONCLUSIONS</b>Women have a higher rate than men in Southwest China. Geriatric patients are more than the young and middle-aged patients. The femoral neck fractures, intertrochanteric fractures and femoral head fractures are in descending orders according to the proportion of the three different hip fractures.</p>

Effects of simvastatin on PDGF-BB and serum-induced proliferation of vascular smooth muscle cells and on the expression of tumor suppressor gene PTEN / 中国病理生理杂志

AIM: To observe the effect of simvastatin on the proliferation of vascular smooth muscle cells(VSMCs) induced by serum and growth factor PDGF-BB and the effect of simvastatin on the expression of PTEN,a important regulator of G 1/S cell cycle transition. METHODS: The DNA synthesis was determined by -TdR incorporation, cell cycle was examined with flow cytometry, the protein level of PTEN was measured by Western blot method. RESULTS: (1)Simvastatin inhibited -TdR incorporation in a dose dependent manner. (2) Flow cytometric DNA analysis revealed that simvastatin induced significantly enhancement of G 0/G 1 phase and decrease in S phase VSMCs.(3)Simvastatin increased protein level of PTEN and mevalonate, a metabolite of HMG-COA, reversed the effect of simvastatin on PTEN protein expression. CONCLUSION: Simvastatin may inhibit proliferation of VSMCs and retarded cell cycle in G 0/G 1 phase by increasing PTEN expression through inhibiting synthesis of mevalonate.

Apoptosis induced by simvastatin in rat vascular smooth muscle cells through calpain and caspase-3-dependent pathways / 中国病理生理杂志

AIM: Hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors, such as simvastatin, have been shown to reduce atherosclerotic cardiovascular morbidity and mortality by mechanisms unrelated to its lipid-lowering effect. Several studies have shown that simvastatin induces apoptosis in a varieties of cell lines including vascular smooth muscle cells (VSMC). The aim of this study was to investigate the signal pathways involved in apoptosis induced by simvastatin. METHODS: Cultured VSMC were treated with simvastatin. Calpain activity was determined by measuring Ca 2+ ionophore-specific calpain substrate (suc-LLVY-AMC), caspase-3 activation was detected by Western blot, and apoptotic changes were distinguished by annexin Ⅴ binding and DNA laddering. RESULTS: After incubated with 30 ?mol/L simvastatin for 8 h, calpain activity had a marked increase ( P