[Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma].

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

[Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma].

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34ßE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34ßE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

[Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma].

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Identification of hub genes correlated with diabetic retinopathy via bioinformatics methods.

OBJECTIVE: The aim of this study was to identify the hub genes and uncover the molecular mechanisms of diabetic retinopathy (DR). MATERIALS AND METHODS: We used the Gene Expression Omnibus (GEO) dataset GSE60436 in our study. After screening for differentially expressed genes (DEGs), we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. Subsequently, a protein-protein interaction (PPI) network was constructed using the Search Tool for Retrieval of Interacting Genes (STRING) database and visualized using the Cytoscape software. Finally, we identified 10 hub genes by cytoHubba plugin. RESULTS: A total of 592 DEGs were identified, including 203 up-regulated genes and 389 downregulated genes. The DEGs were mainly enriched in visual perception, photoreceptor outer segment membrane, retinal binding, and PI3K-Akt signaling pathway. By constructing a protein-protein interaction (PPI) network, 10 central genes were finally identified, including CNGA1, PDE6G, RHO, ABCA4, PDE6A, PDE6B, NRL, RPE65, GUCA1B and AIPL1. CONCLUSIONS: CNGA1, PDE6G, RHO, ABCA4, PDE6A, PDE6B, NRL, RPE65, GUCA1B, and AIPL1 may be potential biomarkers and therapeutic targets for DR.

[Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia].

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

[Applications of the NDR and DIAL models for risk prediction on cardiovascular disease in patients with type 2 diabetes in Ningbo].

Objective: To validate the performance of cardiovascular risk prediction models based on the Sweden National Diabetes Register (NDR) and Diabetes Lifetime-perspective prediction (DIAL) model for assessing risks of 5-year and 10-year cardiovascular disease (CVD) among Chinese patients with type 2 diabetes. Methods: Based on the Chinese Electronic Health Records Research in Yinzhou study, 83 503 patients with type 2 diabetes aged 30-75 years without a history of CVD at baseline were included from January 1, 2010 to December 31, 2020. Recalibrated NDR model was used to estimate 5-year risk, while the recalibrated DIAL model was used to predict 5-year and 10-year risks. The competing events adjusted Kaplan-Meier analysis was used to obtain the observed cardiovascular events. Discrimination C statistics evaluated model accuracy, calibration χ2 value, and calibration plots. Results: Through a median follow-up of 7.0 years, 7 326 cardiovascular events, and 2 937 non-vascular deaths were identified among a total of 83 503 subjects. The recalibrated NDR model overestimated 5-year risk by 39.4% in men and 8.6% in women, whereas the overestimation for the recalibrated DIAL model was 14.6% in men and 50.1% in women. The DIAL model had a better discriminative ability (C-statistic=0.681, 95%CI: 0.672-0.690) than NDR model (C-statistic=0.667, 95%CI: 0.657-0.677) in 5-year risk prediction for men, and the models had a similar ability for women (C-statistic=0.699, 95%CI: 0.690-0.708 for NDR and C-statistic=0.698, 95%CI: 0.689-0.706 for DIAL). The prediction accuracy of the DIAL model was improved in the 10-year risk, with the underestimation being 1.6% for men and the overestimation being 12.8% for women. Conclusions: Both recalibrated NDR and DIAL models overestimated 5-year cardiovascular risk in Chinese patients with type 2 diabetes, while the higher overestimation was shown using the DIAL model. However, the improvement was found in predicting 10-year CVD risk using the DIAL model, which suggested the value of lifetime risk prediction and indicated the need for research on the lifetime risk prediction model for cardiovascular risk assessment in Chinese patients with type 2 diabetes.

[The method of determination for butyronitrile and isobutyronitrile in the air of workplace by dissolved desorption-gas chromatography].

Objective: To establish a method for the determination of butyronitrile and isobutyronitrile in the air of workplace by gas chromatography. Methods: In March 2020, butyronitrile and isobutyronitrile in the air of workplace was collected by silica gel, eluted with methanol, separated and determined by gas chromatogram with flame ionization detector, the characteristics of determination of nitrile and isobutyronitrile by gas chromatography were analyzed. Results: The limit of detection for butyronitrile and isobutyronitrile was 0.33 µg/ml. The linear range of butyronitrile determined by this method was 1.60-1600.00 µg/ml, y=2.295x-3.480, and the coefficient correlation was 0.99998, and the minimum detection concentration was 0.22 mg/m(3) (collected sample volume was 1.50 L) . The within-run precisions were 2.43%-4.12%, the between-run precisions were 1.72%-3.70%, and the desorption rates were 93.26%-98.41%. The linear range of isobutyronitrile determined by this method was 1.52-1520.00 µg/ml, y=2.208x-0.102, and the coefficient correlation was 0.99998, and the minimum detection concentration was 0.22 mg/m(3) (collected sample volume was 1.50 L) . The within-run precisions were 2.52%-3.22%, the between-run precisions were 1.20%-3.82%, and the desorption rates were 96.85%-102.50%. The sealed samples could be stored at least 10 days at room temperature without significant loss. Conclusion: The method has the advantages of good precision, high sensitivity and simple operation. It is suitable for the simultaneous determination of butyronitrile and isobutyronitrile in the air of workplace.

[Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model].

OBJECTIVE: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. METHODS: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. RESULTS: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. CONCLUSION: Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

[Analysis of clinical features and prognosis in patients with primary Sjögren's syndrome and autoimmune liver disease].

OBJECTIVE: To analyze the clinical features and prognosis in patients with primary Sjögren's syndrome (pSS) and autoimmune liver diseases (ALD). METHODS: A retrospective analysis of clinical manifestation and prognosis was performed in patients with ALD or without ALD during the three years (February 2014 to December 2017). RESULTS: Totally, 203 patients with pSS were included in this study, 68 patients had ALD (31 patients with autoimmune hepatitis, 37 patients with primary biliary cholangitis), while 135 patients did not have ALD. There were no differences between the two groups regarding age, gender, clinical manifestations, such as dry mouth, dry eyes, pain, fatigue, lymphadenopathy, glandular swelling, cutaneous involvement, lung involvement, and renal involvement, and the incidence rate of other autoimmune diseases, such as autoimmune thyroid disease, rheumatoid arthritis, and vasculitis. There were also no differences in the titer of antinuclear antibody (ANA), the positive rates of anti-Sjögren's syndrome A antibody (SSA), SSA52, and anti-Sjögren's syndrome B antibody (SSB), and at the levels of erythrocyte sedimentation rate and C-reactive protein between the two groups. Most importantly, the pSS patients with ALD had a shorter disease course, a higher positive rate of anti-mitochondrial M2 antibody (AMA-M2) and anti-centromere antibody, a higher level of IgG and IgM, a lower level of complement 3, and a decreased number of blood cells. They also had a higher level of liver related serum index, such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and total bilirubin, direct bilirubin, indirect bilirubin, a higher incidence rate of liver cirrhosis, an increased death incident (the mortality was 13.24% in the pSS patients with ALD, while 2.96% in the controls, P=0.013), and a worse prognosis. Binary Logistic regression analysis revealed that liver cirrhosis, the EULAR Sjögren's syndrome disease activity index (ESSDAI) scores and the level of total bilirubin were the prognostic factors of mortality in the pSS patients with ALD. The survival curve was estimated by the Kaplan-Meier method. It demonstrated that the pSS patients with ALD had a lower survival rate when compared with the controls. CONCLUSION: The patients with both pSS and ALD will suffer from a more severe disease and a higher death incident. We should pay more attention to these patients and provide a better symptomatic treatment for them during clinical practice.

[Value of dynamic MRI in monitoring the microenvironmental changes of anti-vascular therapy in a xenograft model].

Objective: To explore the feasibility of dynamic-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent MRI (BOLD-MRI) in assessing the hemodynamics and tumor aggressiveness during treatment. Methods: The colon cancer xenograft model was established in BALB/C nude mice with HCT116 cell line. Sixteen nude mice were randomly divided into treatment and control groups (aged 6 to 8 weeks, weighted 15 to 18 g, Certificate No. 11400700325797), which were treated with bevacizumab and saline by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th day. DCE-MRI and BOLD-MRI were performed before and on the 3th, 6th, 9th, 12th, and 15th day after treatment. The vascular maturity and microenvironment hypoxia were confirmed by pathology. Results: The tumor volume of treatment group was significantly smaller than that of control group after 15 days ((712±43) vs (1 051±112) mm(3),P<0.01).The measurements of K(trans) were (0.135±0.005),(0.147±0.006),(0.175±0.009),(0.161±0.006), (0.140±0.005),(0.116±0.008)/min (F=81.386, P<0.01); K(ep) were (0.788±0.030),(0.804±0.036),(0.983±0.059), (1.105±0.091),(0.840±0.047),(0.786±0.041)/min(F=45.901,P<0.01);Ve were (0.652±0.006), (0.559±0.026), (0.466±0.016), (0.286±0.027), (0.363±0.020), (0.246±0.033) (F=384.290, P<0.01) and R2* values were (24.813±0.961), (24.675±1.070), (21.425±1.371), (17.850±0.885), (24.613±0.640), (27.013±0.734)/s (F=89.323, P<0.01) showed different trends with time in the treatment group, and the differences were statistically significant. The K(trans) values and tumor vessel maturity index (VMI) were higher than baseline values during 3-12 d after treatment. CD31 positive staining rate and VMI had the strongest correlations with K(trans) values (r=0.854 and 0.795), followed by AUC(180) (r=0.750 and 0.808), Ve (r=0.744 and 0.712) and K(ep) values (r=0.729 and 0.758), all P<0.05. R2* value positively correlated with the positive staining rate of HIF-1α and fibronectin (r=0.810 and 0.816), all P<0.05. Conclusion: DCE-MRI and BOLD-MRI are adequate to observe the tumor perfusion and hypoxia during anti-vascular treatment, and the R2* value can predict the tumor metastatic potential during the process of vascular normalization.

[A study on the features and influences of first physiology translation Ti Yong Shizhang].

In 1884, Kong Qinggao translated Huxley's Lessons in Elementary Physiology into a Chinese version, namely Ti Yong Shizhang. The book, with John Kerr Proofreading, turns out to be the first modern physiologic textbookin Chinese. Even so, this translation has long been ignored by researchers in the history of physiology and with no systematical introduction.The Chinese version was basically true to the western original featuring comprehensive knowledge and profound theories, with only a few pieces of content deleted and minimal order adjusted. The printing of 85 illustrations was as much refined as the original ones. The newly coined physiological terms in Chinese version had a certain impact at the time. As the first physiologic textbook to cultivate the earliest modern physicians, its copies were spread in the intellectual community. Conclusively, Ti Yong Shizhang played a significant role in the spread of Western physiology in China.

[Clinical short-term and long-term efficacy of endoscopic submucosal dissection in the treatment of early low rectal cancer and precancerous lesions].

Objective: To evaluate the short-term and long-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early low rectal cancer and precancerous lesions. Methods: Inclusion criteria: (1) Distance from the lower margin of tumor to the anal was ≤ 5 cm. (2) Early low rectal cancers were any size rectal epithelial tumors with infiltration depth limited to the mucosa and submucosa, which were diagnosed by postoperative pathology as high-grade intraepithelial neoplasia or adenocarcinoma of the rectum with infiltration depth of intramucosal or submucosal cancer (M or SM stage). (3) Precancerous lesions included adenoma and low-grade intraepithelial neoplasia of the rectum. (4) Patients received ESD treatment. Patients with tumor invasion depth over submucosa by pathology were excluded. From January 2008 to January 2018, 63 patients meeting the above criteria in Peking University First Hospital were enrolled in this descriptive cohort study. The disease characteristics, clinical manifestations, pathological types, treatment time, hospitalization time, en bloc resection rate (resection of the whole lesion), complete resection rate (both the horizontal and vertical incision margins were negative), postoperative complications and follow-up results were analyzed. Cummulative survival rate was calculated by Kaplan-Meier. Results: The diameter of the lesion was (29.0±23.4) mm and the distance from the lesion to the anus was (2.7±1.8) cm. The median operation time was 45.0 (range, 10.0 to 360.0) minutes, the median hospitalization time was 3.0 (range, 2.0 to 12.0) days, en bloc resection rate was 100%, complete resection rate was 96.8% (61/63), and 1 case (1.6%) had postoperative bleeding. The follow-up rate was 87.3% (55/63) and the median follow-up time was 57.9 (range, 15.6 to 121.1) months. No local recurrence was found during the follow-up period and the 5-year survival rate was 100%. Conclusion: Short- and long-term efficacy of ESD are quite good in the treatment of patients with early low rectal cancer and precancerous lesions.

[Influence of subthalamic nucleus deep brain stimulation on cognition and acetylcholine in a rat model of Parkinson's disease].

Objective: To illustrate the effect of subthalamic nucleus deep brain stimulation (STN-DBS)on cognitionand its underlying mechanisms in a rat model of Parkinson's disease (PD). Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (healthy rats, n=10), model group (PD rats, n=10), and stimulation group (PD rats receiving high frequency stimulation, n=10). The cognitive functionof rats was tested through Morris water maze and acetylcholine levels in cortex, hippocampus and striatum have been examined through ELISA. Results: During Morris water mazetest, spatial learning and memory of PD ratsdeteriorated compared with healthy ones, withlonger escape latency[on day 4, (38±14) s vs (20±4) s, P=0.047; on day 5, (32±13) s vs (16±8) s, P=0.032]and shorter time in the platform region[(10±6) s vs (19±5) s, P=0.023], which could be restored by STN-DBS. Similar results demonstrated that the expression of Ach in hippocampus[(1 473±233) s vs (1 950±344) s, P=0.039]and striatum[(1 661±271) s vs (2 240±290) s, P=0.007]was significantly lower in PD rats than those in healthy rats, and STN-DBS treatment reversed this decline to insignificant. Conclusion: The rat model of PD suffer from a decline in cognition, and STN-DBS contributes to cognitive recovery, possibly due to regulating Ach levels in cognition-associated regions of the brain, includinghippocampus and striatum.

[The efficacy of external physical vibration lithecbole in the assistant treatment of the upper urinary tract residual stones: a meta-analysis].

Objective: To determine the clinical effect of Friend-Ⅰ External Physical Vibration Lithecbole (EPVL) by Meta-analysis. Methods: Pubmed, Embase, Medline, Cochrane Library, Chinese National Knowledge Infrastructure were searched for clinical trials comparing EPVL with the conventional treatment. The quality of included studies was assessed and Meta-analysis was conducted by Review Manager 5.3 software. Results: Five randomized or Quasi-randomized controlled trials met the inclusion criteria. The first day stone expulsion rate of EPVL group was superior to the control group (OR=4.95, 95% CI: 3.35-7.32, P<0.000 01). Both one-week (OR=3.13, 95% CI: 1.95-5.04, P<0.000 01) and two-week stone free rate (OR=4.50, 95% CI: 2.02-10.00, P=0.000 2) were statistically higher in the EPVL group than that in the control group. No severe adverse event occurred during the follow-up. Conclusions: Our study suggested that EPVL could be the effective treatment for upper urinary tract residual stone. However, more high quality randomized controlled trials are needed to better affirm this.

The expression of succinate semialdehyde dehydrogenase in the caudal part of the spinal trigeminal nucleus is down-regulated after electrical stimulation of the dura mater surrounding the superior sagittal sinus in conscious rats.

Using two-dimensional gel electrophoresis (2-DE), we examined proteomic changes in the caudal part of the spinal trigeminal nucleus induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus (ES-SSS) in conscious rats. After image analysis of 2-DE gels, nine protein spots of interest were excised from the gels and identified by liquid chromatography-tandem mass spectrometry. Among the nine, succinate semialdehyde dehydrogenase (SSADH) was found to be down-regulated after ES-SSS. This result was validated with Real-time polymerase chain reaction and Western blot analyses. Because SSADH degrades GABA, decreased expression of it increases the local concentration of GABA in the caudal part of the spinal trigeminal nucleus after ES-SSS; this has not been reported before and may participate in the modulation of trigeminovascular headache.

Novel nonsense and frameshift NTRK1 gene mutations in Chinese patients with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is a rare autosomal recessive disorder characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, and mental retardation. It is caused by mutations in the gene coding for neurotrophic tyrosine kinase receptor type 1 (NTRK1; MIM# 191315). We screened two Chinese CIPA cases for mutations in the NTRK1 gene and examined their phenotype. Two novel mutations of the NTRK1 gene and two known mutations were identified. Including our two novel mutations, there are now 62 different NTRK1 gene mutations reported in patients with CIPA. We find that a combination of two null alleles usually leads to the severe phenotype, while the mild form of the CIPA disease is associated with at least one mild allele. Thirty-four among the 62 mutations (55%) are located within the tyrosine kinase domain of the NTRK1 protein. We concluded that the tyrosine kinase domain is a hot spot for mutations.

Enhancement patterns of intrahepatic cholangiocarcinoma: comparison between contrast-enhanced ultrasound and contrast-enhanced CT.

The aim of this study was to compare the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). 40 pathologically proven ICC lesions in 40 patients were evaluated retrospectively with both CEUS and CECT. The enhancement level and pattern in the dynamic phases on both CEUS and CECT were analysed. The diagnostic results of CEUS and CECT before pathological examination were also recorded. During arterial phases, the number of lesions that appeared as (i) peripheral irregular rim-like hyperenhancement, (ii) diffuse heterogeneous hyperenhancement, (iii) diffuse homogeneous hyperenhancement and (iv) diffuse heterogeneous hypoenhancement were 19 (47.5%), 9 (22.5%), 5 (12.5%) and 7 (17.5%), respectively, on CEUS, and 22 (55.0%), 3 (7.5%), 2 (5.0%) and 13 (32.5%), respectively, on CECT (p = 0.125). In the portal phase, the number of lesions showing hyperenhancement and hypoenhancement were 1 (2.5%) and 39 (97.5%), respectively, on CEUS, and 15 (37.5%) and 25 (62.5%) on CECT (p = 0.0001). CEUS made a correct diagnosis in 32 (80.0%) lesions before pathological examination; CECT made a correct diagnosis in 27 (67.5%) lesions (p = 0.18). In conclusion, the enhancement patterns of ICC on CEUS were consistent with those on CECT in the arterial phase, whereas in the portal phase ICC faded out more obviously on CEUS than on CECT. CEUS had the same accuracy as CECT in diagnosing ICCs, and so can be used as a new modality for the characterization of ICC.