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OBJECTIVE To determine the risk for pulmonary embolism (PE) and explore the relationship between the site of thrombosis and PE in patients with acute lower extremity deep vein thrombosis (DVT). METHODS 1585 hospitalized patients first diagnosed with acute lower extremity DVT were investigated retrospectively. The patients were divided into two groups: the non-PE group (Group 1) and the PE group (Group 2). Then, Group 2 was divided into two subgroups: asymptomatic pulmonary embolism (asPE, Group 2a) and symptomatic pulmonary embolism (sPE, Group 2b). Kaplan-Meier curves and logistic regression analysis were used to explore the relevant risk factors for PE. RESULTS Among 1585 patients, 458 patients suffered from PE, accounting for 28.9%. 102 (22.3%) of them had the typical clinical manifestations of PE and were defined as sPE, and the remaining 356 (77.7%) patients were classified as asPE. Patients with proximal lower extremity DVT were significantly more predominant in the PE group than in the non-PE group (92.8% vs. 86.2%, p

Heat stress is known to negatively impact the reproductive process of livestock, which inevitably leads to a decline in animal fertility. Nuclear factor E2-related factor 2 (Nrf2) is an inducible transcription factor, which is essential for maintaining redox signal transmission against oxidative stress. However, there is no reliable research on the response mechanism of Sertoli Cells (SCs) against heat stress and the activation of Nrf2 when SCs are exposed to heat stress. Here, we used primary mouse SCs and SCs line TM4, along with Nrf2 specific inhibitor to determine the reaction mechanism of SCs to maintain intracellular redox homeostasis and self-survival by activating Nrf2. We found that acute heat stress only affected the vitality of SCs and the expression of functional molecules (tight junction-associated proteins and lactate dehydrogenase A [LDHA]) but did not cause cell apoptosis. When Nrf2 was inhibited, more cell death occurred in TM4 cells post heat stress treatment, along with a greater decrease in cell viability and a significant increase in intracellular ROS levels. Our study clarified for the first time the protective effect of Nrf2 activation on heat stress-induced SCs damage. It explained the possible reasons or mechanisms involved in the survival of SCs, the critical protective cells in the testis, which were not affected by heat stress. This study further improved the response mechanism of SCs in the reproductive injury caused by a high-temperature environment.

BACKGROUND This article investigated whether robotic-assisted liver surgery versus laparoscopic liver surgical treatment of hepatocellular carcinoma (HCC) has similar or different short- and long-term clinical outcomes. METHODS A total of 3049 patients from the National Cancer Database who received minimally invasive surgery (ie, robotic or laparoscopic surgery) for stage I HCC cancers between 2010 to 2015, of which 123 had robotic and 2926 had laparoscopic surgeries performed, were identified. Logistic regression was applied to evaluate short-term outcomes. Cox proportional hazards models were applied to estimate all-cause mortality at 1-year, 3-years, and 5-years after surgery, adjusting for potential confounders. Propensity score-matched analyses were conducted to compare long-term outcomes between robotic and laparoscopic surgeries. RESULTS Robotic surgery was associated with improved overall survival, with 1-, 3-, and 5-year survival rates (SRs) of 0.92, 0.75, and 0.63 compared with laparoscopic surgery SRs of 0.86, 0.60, and 0.45, respectively (P value

High nut consumption is associated with reduced total and certain cause-specific mortality in general populations. However, its association with cancer outcomes among long-term breast cancer survivors remains unknown. We examined the associations of nut consumption (including peanuts and tree nuts), assessed at 5-year postdiagnosis, with overall survival (OS) and disease-free survival (DFS) among 3449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study, applying Cox regression analysis. During a median follow-up of 8.27 years post dietary assessment, there were 374 deaths, including 252 breast cancer deaths. Among 3274 survivors without previous recurrence at the dietary assessment, 209 developed breast cancer-specific events, that is, recurrence, metastasis or breast cancer mortality. At 5-year post dietary assessment (ie, 10-year postdiagnosis), regular nut consumers had higher OS (93.7% vs 89.0%) and DFS (94.1% vs 86.2%) rates. After multivariable adjustment, nut consumption was positively associated with OS (Ptrend = .022) and DFS (Ptrend = .003) following a dose-response pattern, with hazard ratios (95% confidence interval) of 0.72 (0.52-1.05) for OS and 0.48 (0.31-0.73) for DFS, for participants with greater than median nut intake compared with nonconsumers. The associations did not vary by nut type. Stratified analyses showed that the associations were more evident among participants with a higher total energy intake for OS (Pinteraction = .02) and among participants with early stage (I-II) breast cancers for DFS (Pinteraction = .04). The nut-DFS associations were not modified by estrogen receptor/progesterone receptor status or other known prognostic factors. In conclusion, nut consumption was associated with better survival, particularly DFS, among long-term breast cancer survivors.

Gastric cancer is a heterogeneous disease which requires a multimodal approach of management. The Department of Gastrointestinal Surgery at Changhai Hospital, a tertiary hospital in Shanghai, established the gastric cancer multidisciplinary team (MDT) clinic based on the guidance of MDT culture in the year of 2017. Our MDT discussion followed a weekly consultation model, with the full-board discussion held once a month, and mini-board communication and discussion made once a week. The stages of MDT management are: pre-operative treatment plan and preparation, post-operative treatment plan, and follow-up treatment and evaluation. As of March 2021, a total of 296 patients visited the MDT clinic. Majority of the patients were gastric carcinoma patients (273/296, 92.2%). Here, we shared our gastric cancer MDT experiences and summarized our strengths and proposed directions for improvement.

Objective To evaluate the quality of Arnebiae Radix (AR) and Dictamni Cortex (DC) and study the efficacy of herbal extracts of these two herbs on the treatment of allergic contact dermatitis (ACD). Methods Qualitative and quantitative analysis of effective components was performed using High Performance Thin Layer Chromatography (HPTLC), High Performance Liquid Chromatography (HPLC), and HPLC-Quadrupole Time of Flight-Mass Spectrometry (HPLC-QTOF-MS). In vitro allergic ACD 3D model was established by incubating 3D reconstructed human epidermis (RHE) with skin sensitizer, potassium dichromate. A total of 65 gene expression that were associated with ACD, which included 24 antioxidant responsive element (ARE) and 41 SENS-IS genes were quantified by qRT-PCR. More than or equal to 10 ARE genes and 18 SENN-IS genes were induced by 1.3-fold, demonstrating the successful establishment of in vitro ACD model. Oil extracts of AR and DC were applied on the in vitro ACD model to study the efficacy. Results Batch 3 of AR and batch 2 of DC showed presence of all active ingredients with the highest concentrations. Active ingredients of the herbs were extracted using a special oil and formulated into herbal oil extracts. The herbal oil extracts were able to down regulate the induced genes in the in-vitro ACD skin model, bringing the tissue back to homeostatic status. Conclusion The oil extracts showed the potent efficacy of using AR and DC in ACD treatment. The combination study will be done to optimize the formulation ratio which will be developed into a topical cream.

Background Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. Methods We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. Results In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. Conclusions In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Amorphous solid dispersions (ASD) are one of most commonly used supersaturating drug delivery systems (SDDS) to formulate insoluble active pharmaceutical ingredients. However, the development of polymer-guided stabilization of ASD systems faces many obstacles. To overcome these shortcomings, co-amorphous supersaturable formulations have emerged as an alternative formulation strategy for poorly soluble compounds. Noteworthily, current researches around co-amorphous system (CAS) are mostly focused on preparation and characterization of these systems, but more detailed investigations of their supersaturation (“spring-parachute“ process), stability, in vivo bioavailability and molecular mechanisms are inadequate and need to be clarified. In present study, we chose pharmacological relevant BCS II drugs to fabricate and characterize “felodipine-indomethacin” CAS. To enrich the current inadequate but key knowledge on CAS studies, we carried out following highlighted investigations including dissolution/solubility, semi-continuous “spring-parachute” process, long-term stability profile of amorphous state, in vivo bioavailability and underlying molecular mechanisms (molecular interaction, molecular miscibility and crystallization inhibition). Generally, the research provides some key information in the field of current “drug-drug” CAS supersaturable formulations.

BACKGROUND In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial. AIM To assess the efficacy and application value of NAC in patients with resectable CRLM. METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software. RESULTS In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004). CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.

Few studies have examined the long-term prognosis of Chinese patients with intracerebral hemorrhage (ICH). This study assessed the clinical characteristics and predictors of vascular events occurring within 5 years after ICH. We included consecutive patients diagnosed with first-ever ICH between June 2013 and December 2014. Based on follow-up data (collected until December 2019), we used multivariable logistic regression to examine the clinical characteristics and long-term predictors of vascular events (including recurrent ICH, ischemic stroke, and acute coronary syndrome) in patients who survived more than 30 days after ICH. Across the 307 patients in our analysis, the 5-year mortality rate was 28.01%. Within 5 years after ICH, major vascular events were observed in 62 patients (17.82%, 95% CI 13.78–21.82%). We observed high incidence of recurrent ICH (8.91%) and ischemic stroke (10.06%), but low incidence of acute coronary syndrome (1.15%). Most cases of recurrent ICH (80.65%) occurred within 3 years after ICH. Age ≥56 years and history of ischemic stroke or transient ischemic attack (TIA) were identified as predictors of cardiovascular and cerebrovascular events. ICH survivors are at high risk of both cardiovascular and cerebrovascular events, especially older patients (≥56 years) and those who experienced ischemic stroke or TIA prior to their first ICH. Recurrent ICH is more likely to occur within the first three years after first ICH than at later times. Clinicians should monitor patients closely for adverse events, particularly during the first three years after initial ICH.

Background Autophagy, a process of self-digestion, is closely related to multiple biological processes of colon cancer. This study aimed to construct and evaluate prognostic signature of autophagy-related genes (ARGs) to predict overall survival (OS) in colon cancer patients. Materials and methods First, a total of 234 ARGs were downloaded via The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, differentially expressed ARGs were identified in colon cancer. The univariate and multivariate Cox regression analysis was performed to screen prognostic ARGs to construct the prognostic model. The feasibility of the prognostic model was evaluated using receiver operating characteristic curves and Kaplan-Meier curves. A prognostic model integrating the gene signature with clinical parameters was established with a nomogram. Results We developed an autophagy risk signature based on the 6 ARGs (ULK3, ATG101, MAP1LC3C, TSC1, DAPK1, and SERPINA1). The risk score was positively correlated with poor outcome and could independently predict prognosis. Furthermore, the autophagy-related signature could effectively reflect the levels of immune cell type fractions and indicate an immunosuppressive microenvironment. Conclusion We innovatively identified and validated 6 autophagy-related gene signature that can independently predict prognosis and reflect overall immune response intensity in the colon cancer microenvironment.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models. VC was induced in vascular smooth muscle cells (VSMCs) by β-glycerophosphate (β-GP), or in rats by subtotal nephrectomy, or in mice by high-dosage vitamin D3. We showed that the expression of BK channels in the artery of CKD rats with VC and in β-GP-treated VSMCs was significantly decreased, which was functionally confirmed by patch-clamp recording. In β-GP-treated VSMCs, BK channel opener NS1619 (20 μM) significantly alleviated VC by decreasing calcium content and alkaline phosphatase activity. Furthermore, NS1619 decreased mRNA expression of ostoegenic genes OCN and OPN, as well as Runx2 (a key transcription factor involved in preosteoblast to osteoblast differentiation), and increased the expression of α-SMA protein, whereas BK channel inhibitor paxilline (10 μM) caused the opposite effects. In primary cultured VSMCs from BK(−/−) mice, BK deficiency aggravated calcification as did BK channel inhibitor in normal VSMCs. Moreover, calcification was more severe in thoracic aorta rings of BK(−/−) mice than in those of wild-type littermates. Administration of BK channel activator BMS191011 (10 mg· kg(−1) ·d(−1)) in high-dosage vitamin D3-treated mice significantly ameliorated calcification. Finally, co-treatment with Akt inhibitor MK2206 (1 μM) or FoxO1 inhibitor AS1842856 (3 μM) in calcified VSMCs abrogated the effects of BK channel opener NS1619. Taken together, activation of BK channels ameliorates VC via Akt/FoxO1 signaling pathways. Strategies to activate BK channels and/or enhance BK channel expression may offer therapeutic avenues to control VC.

BACKGROUND: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. OBJECTIVES: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. METHODS: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development. Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women’s Health and the Shanghai Men’s Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and P values. Results: Eighteen metabolites were associated with gastric cancer risk at P < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; P = 1.89 × 10–4). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; P = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions. Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of Helicobacter pylori infection and other major risk factors. Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer. See related commentary by Drew et al., p. 1601

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Iatrogenic femoral artery pseudoaneurysm caused by invasive procedures is one of the common complications for endovascular interventions. We present a case of a young male with a complex iatrogenic femoral artery pseudoaneurysm as a result of iatrogenic femoral artery puncture. The defective femoral artery was repaired with combined bovine pericardial tube and autologous great saphenous vein grafts. Computed tomography angiography showed the grafts were still patent one year after the surgery.

Multiple clinical trials have shown that monoclonal antibodies (mAbs) against programmed death‐ligand 1 (PD‐1/PD‐L1) can benefit patients with lung cancer by increasing their progression‐free survival and overall survival. However, a significant proportion of patients do not respond to anti‐PD‐1/PD‐L1 mAbs. In the present study, we investigated whether galectin (Gal)‐3 inhibitors can enhance the antitumor effect of PD‐L1 blockade. Using the NSCLC‐derived cell line A549, we examined the expression of Gal‐3 in lung cancer cells under hypoxic conditions and investigated the regulatory effect of Gal‐3 on PD‐L1 expression, which is mediated by the STAT3 pathway. We also explored whether Gal‐3 inhibition can facilitate the cytotoxic effect of T cells induced by PD‐L1 blockade. The effects of combined use of a Gal‐3 inhibitor and PD‐L1 blockade on tumor growth and T‐cell function were also investigated, and we found that hypoxia increased the expression and secretion of Gal‐3 by lung cancer cells. Gal‐3 increased PD‐L1 expression via the upregulation of STAT3 phosphorylation, and administration of a Gal‐3 inhibitor enhanced the effect of PD‐L1 blockade on the cytotoxic activity of T cells against cancer cells in vitro. In a mouse xenograft model, the combination of a Gal‐3 inhibitor and PD‐L1 blockade synergistically suppressed tumor growth. Furthermore, the administration of a Gal‐3 inhibitor enhanced T‐cell infiltration and granzyme B release in tumors. Collectively, our results show that Gal‐3 increases PD‐L1 expression in lung cancer cells and that the administration of a Gal‐3 inhibitor as an adjuvant enhanced the antitumor activity of PD‐L1 blockade., Galectin (Gal)‐3 is involved in the immune response, and highly overexpressed and secreted by lung cancer cells. This study showed that the increased expression of Gal‐3 was induced by hypoxia, which then contributed to immune suppression through the STAT3 pathway in lung cancer. Furthermore, a Gal‐3 inhibitor enhanced the antitumor effect by PD‐L1 blockade through promoting T‐cell infiltration in lung cancer.

Introduction: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. Methods: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. Results: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892–10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410–8.646; p = 0.007). Conclusions: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

In this study, we prepared chemical staple fibers (CSFs) by plasticizing bleached coniferous pulps (BCPs) with 1-allyl-3-methylimidazolium chloride (AMIMCl) under high temperature and pressure. It became a transparent paper after hot-pressing when the mass ratio of AMIMCl to BCPs was 4 : 5. Interestingly, it could be hot-pressed into a new transparent paper after the transparent paper prepared above was torn into pieces. The morphologies of fibers showed that BCPs could be plasticized with AMIMCl. The glass transition temperature (Tg) occurred in CSFs when the mass ratio of AMIMCl to BCPs was 4 : 5 and the corresponding temperature was 149 °C, which was lower than the initial decomposition temperature, therefore, CSFs could achieve workability to a certain extent. The plasticizing effect of AMIMCl on BCPs was further verified by testing the properties of the paper. The plasticizing effects of 1-butyl-3-methylimidazolium chloride (BMIMCl) and 1-ethyl-3-methylimidazolium acetate (EMIMAc) on BCPs showed the universality of the method for preparing CSFs with AMIMCl.

Objective To observe the effects of the thumb-tack needling therapy on knee joint pain and joint function in the elderly patients with knee osteoarthritis (KOA) and compared with medication. Methods A total of 60 patients were randomized into a thumb-tack needling group and a medication group, 30 cases in each one. In the thumb-tack needling group, the therapy with the thumb-tack needle retaining and waiting for qi was adopted. The acupoints were Hedĭng (EX-LE2鹤顶), Neixīyan (内膝眼EX-LE4), Dubi (犊鼻ST35), Xuehai (血海SP10), Liangqiū (梁丘ST34) and Ashi points on the affected side. The needles were retained for 24 h. This therapy was given once every two days, 3 times a week. The treatment for 2 weeks was as one course and consecutive 2 courses of treatment were required. In the medication group, diclofenac sodium sustained release tablets were taken orally, 75 mg each time, once daily, consecutively for 4 weeks. Successively, the score of visual analogue scale (VAS) at the affected knee before treatment, after treatment and 3 months after treatment as well as Lequesne indicator before and after treatment were evaluated. The clinical therapeutic effect was observed in the patients of the two groups after treatment. Results (1) After treatment, VAS scores were reduced as compared with those before treatment in the patients of the two groups (both P Conclusion The thumb-tack needling therapy effectively relieves knee joint pain and improves joint function in the patients and the therapeutic effect is better than medication group. Hence, this therapy deserves to be promoted in clinical practice.

Background The aim of this study was to investigate the neural plasticity in contralesional cortex and the effects of tongxinluo (TXL) in cerebral ischemic rats. Methodology We used stroke-prone renovascular hypertensive (RHRSP) cerebral ischemia rat models to study the effect of TXL and the underlying mechanisms. We performed foot-fault and beam-walking tests to evaluate the motor function of rats after cortical infarction. Biotinylated dextran amine (BDA) was used to track axonal sprouting and neural connections. Results TXL enhanced the recovery of motor function in cerebral infarction rats. TXL increased axonal sprouting in the peri-infarcted area but not in the corpus callosum, indicating in situ origination instead of crossing between cortical hemispheres through the corpus callosum. TXL promoted the sprouting of corticospinal axons into the denervated side of spinal gray matter. The synaptophysin (SYN)-positive intensity in the peri-infarcted area of TXL-treated group was greater than that in the vehicle group. We observed co-localization of SYN with BDA-positive fibers in the denervated spinal cord gray matter in the TXL group, suggesting that axonal remodeling and synaptic connections were promoted by TXL. Conclusion TXL may promote the recovery of neurological function by promoting the axonal remodeling and synapse formation of motor neuronal fibers after focal cortical infarction in hypertensive rats.

Lateral lymph node metastasis in rectal cancer was first reported in the 1950s, since then, there has been an on-going debate about the value of lateral lymph node dissection (LLND) in the management of rectal cancer. We carried out a systematic review and meta-analysis to evaluate the value of LLND for the patients with rectal cancer. To collect clinical studies for the comparison of LLND and non-LLND in patients with rectal cancer, PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar databases were searched from inception to 2019.A total of 26 studies, including 6865 patients were enrolled. Data processing and statistical analyses were performed using Stata V.15.0 software and Review Manager 5.3 software. Outcome measures included the 5-year survival rate, recurrence rate, perioperative outcomes, urinary function, and male sexual function. Regarding efficacy, our meta-analysis results showed no difference in 5-year disease-free survival rate and local recurrences between the two groups, the Hazard Ratio (HR) and 95% confidence interval (CI) was1.07 and 0.89 to 1.28 (P = 0.496),and the Odds Ratio(OR) and 95% CI were 0.90 and 0.76 to 1.06 (P = 0.208), respectively. Concerning safety, the incidence of urinary dysfunction and male sexual dysfunction was significantly increased in the LLND group (OR = 2.14, 95%CI = 1.21–3.79, P = 0.009), and (OR = 4.19, 95%CI = 1.55–11.33, P = 0.005), respectively. In conclusion, LLND did not improve the long-term prognosis of patients with rectal cancer, and was associated with increased urinary dysfunction and male sexual dysfunction.

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59,986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids was not significantly associated with CRC risk. Multivariate hazard ratios (HR) and respective 95% confidence intervals (CI) for quartile 4 vs. quartile 1 were 0.92 (0.74-1.14; Ptrend =0.47) for SFA, 0.95 (0.79-1.16; Ptrend =0.74) for MUFA and 1.18 (0.95-1.46; Ptrend =0.21) for PUFA. No significant association was found for total n-6 PUFA and total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) were associated with 11-12% reduced risk, and linoleic acid (LA) a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men. This article is protected by copyright. All rights reserved.

Aconitine (ACO), a main active ingredient of Aconitum, is well-known for its cardiotoxicity. However, the mechanisms of toxic action of ACO remain unclear. In the current study, we investigated the cardiac effects of ACO and mesaconitine (MACO), a structurally related analog of ACO identified in Aconitum with undocumented cardiotoxicity in guinea pigs. We showed that intravenous administration of ACO or MACO (25 μg/kg) to guinea pigs caused various types of arrhythmias in electrocardiogram (ECG) recording, including ventricular premature beats (VPB), atrioventricular blockade (AVB), ventricular tachycardia (VT), and ventricular fibrillation (VF). MACO displayed more potent arrhythmogenic effect than ACO. We conducted whole-cell patch-clamp recording in isolated guinea pig ventricular myocytes, and observed that treatment with ACO (0.3, 3 μM) or MACO (0.1, 0.3 μM) depolarized the resting membrane potential (RMP) and reduced the action potential amplitude (APA) and durations (APDs) in a concentration-dependent manner. The ACO- and MACO-induced AP remodeling was largely abolished by an INa blocker tetrodotoxin (2 μM) and partly abolished by a specific Na+/K+ pump (NKP) blocker ouabain (0.1 μM). Furthermore, we observed that treatment with ACO or MACO attenuated NKP current (INa/K) and increased peak INa by accelerating the sodium channel activation with the EC50 of 8.36 ± 1.89 and 1.33 ± 0.16 μM, respectively. Incubation of ventricular myocytes with ACO or MACO concentration-dependently increased intracellular Na+ and Ca2+ concentrations. In conclusion, the current study demonstrates strong arrhythmogenic effects of ACO and MACO resulted from increasing the peak INa via accelerating sodium channel activation and inhibiting the INa/K. These results may help to improve our understanding of cardiotoxic mechanisms of ACO and MACO, and identify potential novel therapeutic targets for Aconitum poisoning.

Background The androgen receptor (AR) is increasingly considered as a potential biomarker for breast cancer. Nevertheless, the prognostic value of AR expression in patients with triple-negative breast cancer (TNBC) remains controversial. Therefore, in this meta-analysis we investigated AR expression and its impact on survival outcome. Methods PubMed, Embase, the Cochrane Library, and references of articles were searched to identify relevant studies in which investigated the association between AR expression and prognosis in patients diagnosed with TNBC were published between 1946 and May 2019. The hazard ratio (HR) and confidence interval (CI) of disease-free survival (DFS), overall survival (OS), Distant disease-free survival (DDFS), and Recurrence free survival (RFS) were weighted and pooled by using the fixed-effect or random-effect model based on the heterogeneity of included studies. Results A total of 27 studies, including 4914 TNBC patients were included. AR was expressed in 27.96% (1315/4703) of TNBC patients. In addition, AR expression in TNBC was not associated with disease free survival (DFS) (HR 0.923, 95% CI= 0.671-1.271, p=0.634)), overall survival (OS) (HR 0.910, 95% CI=0.678-1.222, p=0.531), Distant disease-free survival (DDFS) (HR 1.02, 95% CI=0.96-1.08, p=0.489) and Recurrence free survival (RFS) (HR 0.957, 95% CI =0.462-1.982, p=0.906) in TNBC, regardless of confounding factors and heterogeneity existed among included studies. Conclusion In TNBC patients, AR expression is not associated with prognosis.

Background A primary central nervous system lymphoma (PCNSL) presenting with massive hemorrhage is a rare occurrence that is difficult to distinguish from a high-grade glioblastoma. Comprehensive descriptions of the imaging characteristics of such tumors have not yet been reported. Herein, we reported a case of a PCNSL with massive hemorrhage by presenting the imaging features of computed tomography (CT) imaging and structural and perfusion magnetic resonance imaging (MRI). Case summary A 48-year-old man presented with headache lasting for 10 d. CT of the brain showed a round, heterogeneous, high-density lesion with surrounding edema in the right temporal lobe. For further diagnosis, a series of MRI examinations of the brain were subsequently performed, and a hemorrhagic lesion with ring-like enhancement was determined. The whole lesion was relatively hypoperfused on arterial spin labeling images. Surgical resection of the lesion and histopathological examination confirmed that the lesion was a diffuse large B-cell lymphoma with massive hemorrhage. Conclusion PCNSLs with hemorrhage occur very rarely, and structural and perfusion MRI examinations are requested exceedingly rarely. This case provided insight into some characteristics of a hemorrhagic lymphoma on CT and MRI examinations. Perfusion MRI examination may be useful for the differential diagnosis of PCNSLs and other brain tumors.

Surge events are not new to healthcare organizations. Natural disasters, including floods, hurricanes, and pandemics, or human-made scenarios such as mass shootings, all pose challenges to public h...

14-3-3γ is a small protein regulating its target proteins through binding to phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca2+-activated K+ (BK) channels revealed a putative 14-3-3 binding site in the COOH-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. Therefore, we hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We used electrophysiology, Western blot analysis, and coimmunoprecipitation to examine the effects of 14-3-3γ on BK channels both in vitro and in vivo. We demonstrated the interaction of 14-3-3γ with BK α-subunits (BKα) by coimmunoprecipitation. In human embryonic kidney-293 cells stably expressing BKα, overexpression of 14-3-3γ significantly decreased BK channel activity and channel open probability. 14-3-3γ inhibited both total and cell surface BKα protein expression while enhancing ERK1/2 phosphorylation in Cos-7 cells cotransfected with flag-14-3-3γ and myc-BK. Knockdown of 14-3-3γ by siRNA transfection markedly increased BKα expression. Blockade of the ERK1/2 pathway by incubation with the MEK-specific inhibitor U0126 partially abolished 14-3-3γ-mediated inhibition of BK protein expression. Similarly, pretreatment of the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of 14-3-3γ on BK protein expression. Furthermore, overexpression of 14-3-3γ significantly increased BK protein ubiquitination in embryonic kidney-293 cells stably expressing BKα. Additionally, 3 days of dietary K+ challenge reduced 14-3-3γ expression and ERK1/2 phosphorylation while enhancing renal BK protein expression and K+ excretion. These data suggest that 14-3-3γ modulates BK channel activity and protein expression through an ERK1/2-mediated ubiquitin-lysosomal pathway.

BackgroundLittle is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts.MethodsIn this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (FindingsDuring a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked ConclusionsOur study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke—not smoking is always the best choice.

Background China’s standardized training for residents of General Practitioners (GPs) is aimed at providing the postgraduate training for family doctors who will serve the primary health care institutions. The aim of this paper is to investigate the standardized training situation, satisfaction with standardized training, work situation, intention, satisfaction and attitude of GPs who have finished standardized training. Methods This study was undertaken in 6 training hospitals in Gansu province using a questionnaire with 45 questions. Results Approximately 275 residents of GPs were enrolled. Finally, 263 residents completed the questionnaire (95.64% response rate), including 133 females (50.57%) and 130 males (49.43%) with an average age of 28 years (standard deviation, 1.93 years; range, 25–36 years). Additionally, 56.65% were single and 43.35% were married. Of all subjects, 92.40% residents had obtained certification of standardized training for residents of GPs and only 39.54% residents were satisfied with monthly income during training. There were 171 oriented rural medical graduates, of whom, only 42.69% expressed the willing to continue working in the primary health care institutions after the serve time (6 years) expired. Around 86.31% of residents of GPs who had finished standardized training got jobs with more than half serving in the primary health care institutions. For medical institutions and sanitary bureau were clear about general medicine policies, only 29.96% subjects registered as GPs. Among the residents in general practice department, 68.42% were engaged in the diagnosis and treatment of common disease and frequently-occurring diseases as well as referral of patients. The percentage of residents who were satisfied with the job and income were 30.40 and 14.98%, respectively. Conclusion Standardized training for residents of GPs in China is gradually improving. In order to cultivate more GPs and increase their willing to serve in the primary health care institutions, it is necessary to formulate and execute better policy of GPs, publize general medicine and improve the training quality.