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Background. Various studies have produced contradictory results on the prognostic role of the CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Although a meta-analysis published in 2014 reported a worse prognosis of CIMP among CIMP-high (CIMP-H) CRC patients, the sample sizes of the major included studies were small. In this study, we included the most recent studies with large sample sizes and performed an updated meta-analysis on the relationship between CIMP and CRC prognosis. Methods. A search of MEDLINE, Web of Science, and Cochrane for studies related to CIMP and CRC published until July 2021 was conducted based on the PICO (participant, intervention, control, outcome) framework. Data extraction and literature analyses were performed according to PRISMA standards. Results. In the present update, 36 eligible studies (20 recently published) reported survival data in 15315 CRC patients, 18.3% of whom were characterized as CIMP-H. Pooled analysis suggested that CIMP-H was associated with poorer overall survival (OS) ( hazard ratio HR = 1.37 , 95% CI: 1.26–1.48) and disease-free survival/progression-free survival/recurrence-free survival (DFS/PFS/RFS) ( HR = 1.51 , 95% CI: 1.19–1.91) among CRC patients. Subgroup analysis based on tumor stage and DNA mismatch repair (MMR) status showed that only patients with stages III-IV and proficient MMR (pMMR) tumors showed a significant association between CIMP-H and shorter OS, with HRs of 1.52 and 1.37, respectively. Three studies were pooled to explore the predictive value of CIMP on CRC patient DFS after receiving postoperative chemotherapy, and no significant correlation was found. Conclusion. CIMP-H is associated with a significantly poor prognosis in CRC patients, especially those with stage III-IV and pMMR tumors. However, the predictive value of CIMP needs to be confirmed by more prospective randomized studies.

Purpose. Based on meta-analysis to explore the effect of physical exercise on relieving the anxiety of the elderly. Methods. The retrieval time was published in the domestic and foreign literatures on the effect of physical exercise on the anxiety of the elderly published from 2005 to 2021. The random effects model was used to evaluate the mean standard deviation of the scores of the intervention group on reducing the anxiety level of the elderly before and after the test. According to the inclusion and exclusion criteria, the articles were screened, quality evaluated, and data extracted, and the literature was meta-analyzed by RevMan5.3. Results. In meta-analysis and systematic review, 17 papers finally met the inclusion criteria. After sensitivity analysis, the random effects model ( MD = 8.00 , 95% CI (6.90, 9.10), Z = 14.23 ( P < 0.00001 )) and the fixed effects model ( MD = 7.71 , 95% CI (6.98, 8.43), Z = 20.72 ( P < 0.00001 )) show that physical exercise has a positive and significant effect on the anxiety of the elderly. Conclusion. Physical exercise plays an important role in reducing the anxiety of the elderly. Therefore, regular physical exercise can be regarded as part of the elderly pension plan, but more high-quality research is needed to further explore the impact of physical exercise on elderly anxiety.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis characterized by high edema in the stroma, albumin deposition, and formation of pseudocysts. The pathogenesis of CRSwNP is not yet fully understood. Regulatory T (Treg) cells are a subset of CD4+ T cells that play a suppressive immunoregulatory role in the process of CRSwNP. Recent studies have found that there was a significant reduction in Treg cells in polyp tissues, which leads to the onset of CRSwNP. An imbalance between Th17 and Treg cells can also aggravate inflammation toward the Th2 type. This review focuses on our understanding of the function and role of Treg cells and their regulatory factors and clinical significance in CRSwNP. We also summarize the current drug treatments for CRSwNP with Tregs as the potential therapeutic target, which will provide new ideas for the treatment of CRSwNP in the future.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Intrauterine growth restriction (IUGR), one of the major complications of pregnancy, is characterized by low birth weight and results in higher risks for long-term problems including developing metabolic and cardiovascular diseases. Short-chain fatty acids (SCFAs), especially propionate, have been reported to correct glucose and lipid disorders in metabolic diseases. We hypothesized that maternal propionate supplementation could prevent glucose and lipid metabolic disturbance in hypoxia-induced IUGR. Here, in our study, maternal hypoxia was induced from gestational day (GD) 11 to GD 17.5 to establish an IUGR mouse model. Maternal propionate treatment reversed reduced birth weight in male IUGR offspring. Hepatic transcriptomics demonstrated that SP treatment significantly lowered glucose and lipid metabolism-related genes (

BACKGROUND The advantages and disadvantages of robotic technology compared with conventional surgery for low rectal cancer have been discussed extensively. However, a few studies on the efficacy of total mesorectal excision (TME) with different robotic technologies have been reported. The aim of this study was to evaluate the efficacy of two types of robot-assisted TME (R-TME) compared with laparoscopic TME (L-TME). METHODS A prospective comparative study was conducted comparing da Vinci R-TME, Micro Hand S R-TME, and L-TME for rectal cancer. This study was registered with "Clinicaltrials.gov" (ID: NCT02752698) and approved by the Association for the Accreditation of Human Research Protection Program (AAHRPP) (Project number: T16007). Between January 2017 and May 2019, patients with rectal cancer (cT1-3NxM0) were prospectively registered in the Third Xiangya Hospital. The integrity of the TME sample served as the primary outcome. Secondary outcomes included the involvement of the circumferential and distal resection margins (CRM and DRM), number of lymph nodes retrieved, blood loss, operative time, conversion rate, comprehensive complication index score, the International Prostate Symptom score, the International Index of Erectile Function, and the Female Sexual Function Index. RESULTS Of 134 patients with rectal cancer (74 males, mean age [SD] 59.1 ± 8.27 years), 46 patients underwent laparoscopic TME, 45 patients underwent da Vinci R-TME, and 43 patients underwent Micro Hand S R-TME. There were no differences in results between the two types of R-TME. Compared with laparoscopic TME, significant reductions in blood loss (median 65.50 ml da Vinci; median 66.54 ml Micro Hand S vs median 95.04 ml L-TME p = 0.037 and p = 0.041, respectively) and conversion rate (2.2% da Vinci; 2.3% Micro Hand S vs 6.8% L-TME p = 0,040 for the comparison daVinci L-TME and p = 0.038 for the comparison Micro Hand S vs. L-TME) with da Vinci Si and Micro Hand S R-TME were noted, and significant increases in operation time (230.05 min da Vinci; 235.03 min Micro Hand S vs. 205.53 min L-TME p = 0.045 and p = 0.043, respectively) was observed. Additionally, more patients underwent TME with sphincter-preserving methods in the two R-TME groups based on the type of operation (da Vinci 97.7%; Micro Hand S 97.9% vs. L-TME 82% resulting in p = 0.033 for the comparison daVinci L-TME and p = 0.035 for the comparison Micro Hand S vs. L-TME). In comparison with L-TME, there was a larger number of lymph nodes retrieved (da Vinci mean 17.54; Micro Hand S mean 17.32 vs. L-TME mean 14.96 p = 0.031 for the comparison daVinci L-TME and p = 0.033 for the comparison Micro Hand S vs L-TME) and less blood loss (da Vinci mean 65.50 ml; Micro Hand S mean 66.54 ml vs. L-TME mean 95.04 ml, p = 0.037 for the comparison daVinci L-TME and p = 0.041 for the comparison Micro Hand S vs. L-TME), and incidence of severe postoperative complications was similar among three TME groups except for the earlier recovery of urogenital function (mean IPSS score da Vinci 7.73±1.35; Micro Hand S7.75±1.47 vs L-TME 14.26±1.41 p

Background More information about the impacts of comprehensive pharmaceutical care program (CPCP) on the identification and resolution of drug-related problems (DRPs) is needed. This study aimed at researching the characteristics of DRPs in osteoporosis patients and evaluating the effect of CPCP in identifying and addressing DRPs. Methods We performed a prospective interventional study in a teaching hospital. CPCP was established and conducted to identify and resolve DRPs by a multidisciplinary team (MDT) based on the Pharmaceutical Care Network Europe (PCNE) classification V9.0. Six pharmacists and one doctor worked directly in the study. All data was obtained from electronic medical records, direct observation and visits. The statistical analyses were performed using the SPSS Statistics software version 26.0. Results Two hundred nineteen patients with osteoporosis were included in the final analysis. A total of 343 DRPs were identified, with an average of 1.57 DRPs per patient. The most common DRPs identified were “treatment safety P2” (66.8%; 229/343), followed by “other P3” (21.0%; 72/343) and “treatment effectiveness, P1” (12.2%; 42/343). The primary causes of DRPs were “dose selection C3” (35.9%; 211/588), followed by “drug use process C6” (28.9%; 170/588) and “drug selection C1” (12.6%; 74/588). Seven hundred eleven interventions were proposed to address the 343 DRPs, with an average of 2.1 interventions per DRP. The acceptance rate reached 95.9, and 91.0% of these accepted interventions were fully implemented. As a result, only 30 DRPs were unsolved before discharge. Additionally, the number of drugs was found to be associated with the number of DRPs significantly (p = 0.023). Conclusion DRPs frequently occurred in hospitalized osteoporosis patients. CPCP could be an effect option to solve and reduce DRPs for osteoporosis patients and should be implemented widely to increase patient safety.

Subarachnoid hemorrhage (SAH) can cause acute neuronal injury and chronic neurocognitive deficits; biomarkers reflecting its associated neuronal injury are of potential prognostic value. Sortilin, a member of the vacuolar protein sorting 10p (Vps10p) family, is enriched in neurons and is likely involved in neurodegenerative diseases. Here, we explored sortilin in the cerebrospinal fluid (CSF) as a potential biomarker for early neuronal injury after SAH. Sortilin levels in the CSF of SAH patients (n = 11) and controls (n = 6) were analyzed by immunoblot. SAH rats surviving 3–72 h (h) were evaluated neurologically, with their brain and CSF samples examined histologically and biochemically. Sortilin protein ~100 kDa was detected in the CSF from SAH patients only, with its levels correlated to Hunt-Hess scale. Rats in the SAH groups showed poorer Garcia score and beam balancing capability than sham controls. Sortilin ~100 kDa was detectable in the CSF of the SAH, but not sham, animals. Levels of sortilin ~100 kDa and fragments ~40 kDa in cortical lysates were elevated in the SAH relative to control rats. Levels of cortical glial fibrillary acidic protein (GFAP) were also elevated in the SAH rats. In immunohistochemistry, the pattern of sortilin labeling in the brain was largely comparable between the SAH and control rats, whereas an increased astrocytic GFAP immunolabeling was evident in the former. Together, these results suggest that SAH can cause an early and remarkable rise of sortilin products in CSF, likely reflecting neuronal change. Sortilin could be further explored as a potential biomarker in some brain disorders.

ObjectivesThis study aimed to identify the potential risk factors for small airway dysfunction (SAD) in non-smokers with chronic cough.MethodsNon-smokers with chronic cough who underwent lung function tests at Xiangya Hospital from May 2019 to May 2020 were enrolled, and divided into the derivation and validation cohorts based on their hospital admission time. SAD was determined based on the presence of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow at 50% of forced vital capacity (FVC), and forced expiratory flow at 75% of FVC. Clinical data of these patients were collected. Risk factors for SAD were identified by logistic regression analysis in the derivation cohort and further confirmed in the validation cohort.ResultsIn total, 316 patients (152 in the non-SAD group and 164 in the SAD group) were included in the derivation cohort. Compared with the non-SAD group, the SAD group had a higher proportion of female patients (82.3 vs. 59.2%, P < 0.001), was more commonly exposed to second-hand smoke (SHS) (61.6 vs. 27.6%, P < 0.001), and tended to be older (median age, 45.5 vs. 40.0 years old, P = 0.004). The median FVC, forced expiratory volume in one second (FEV1) % pred, FEV1/FVC ratio, and peak expiratory flow (PEF) % pred were slightly lower in the SAD group. Multivariable logistic analysis showed that exposure to SHS was an independent risk factor (OR 4.166 [95% CI 2.090–8.302], P < 0.001) for SAD in non-smokers with chronic cough after adjusting for related variables. In the validation cohort (n = 146), patients with SHS exposure had a relative risk of 1.976 (95% CI 1.246–3.135, P = 0.004) for SAD compared to those without SHS exposure. Multivariable logistic analysis consistently confirmed that exposure to SHS was an independent risk factor (OR 3.041 [95% CI 1.458–6.344], P = 0.003) for SAD in non-smokers.ConclusionsExposure to SHS is independently associated with a higher risk of SAD in non-smokers with chronic cough. Reduction in SHS exposure may ameliorate lung function, thus lowering the risk of irreversible airway obstruction.

The effectiveness of a 3rddose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rddose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4thdose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4thdose is inferior to that after the 3rddose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4thdose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.

Now cancer-related fatigue is gradually being emphasized, which is a common symptom in cancer patients. During long-term radiotherapy, the emotion of patients will be affected directly, and inevitably produce cancer-caused fatigue needle symptoms. Moreover, the weakness and fatigue are always produced simultaneously, which are harmful to patients’ prognosis level of their overall survival quality. The acupuncture has a helpful effect on improving the Chinese medical evidence of side effects caused by radiotherapy and chemotherapy in tumor patients. In this paper, we model the effect of acupuncture on cancer fatigue after chemotherapy in gynecologic oncology patients through data analysis, so as to effectively analyze the degree of cancer fatigue after chemotherapy in patients.

Lung cancer is the most common cancer and one of the main causes of cancer-related deaths, presenting in most cases as metastatic disease. Given the frequent gene mutation and/or signaling deregulation in lung adenocarcinoma, identifying novel factors or agents that target these signaling pathways may be promising strategies for lung adenocarcinoma therapy. Herein, we identified inhibitor of DNA binding 2 (ID2) as an aberrantly downregulated gene in lung adenocarcinoma. ID2 overexpression not only suppressed the viability, colony formation ability, and migration ability of lung adenocarcinoma cells but also decreased the protein levels of N-cadherin, MMP2, MMP9 and the phosphorylation levels of AKT and mTOR. The effects of PI3K/AKT/mTOR signaling agonist on lung adenocarcinoma cells were opposite to those of ID2 overexpression, partially reversing the effects of ID2 overexpression. In these experimental tissue samples, ID2 protein levels and mRNA expression were also down-regulated compared with those in adjacent non-cancerous tissues. Altogether, these findings indicated that ID2 exerts its tumor-suppressive effects on the malignant behavior of lung adenocarcinoma cells by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. Restoration of ID2 expression in lung adenocarcinoma cells may improve the therapeutic efficacy of lung adenocarcinoma therapies.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 μM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 μM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 μM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 μM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe

Because the recovery of genitourinary function after total mesorectal excision (TME) is affected by multiple factors, the role of robot-assisted TME technology in postoperative function in previous studies is still controversial. Our study aimed to evaluate the impact of robotic technology on the recovery of genitourinary function after TME for rectal cancer by analysing the correlations between influencing factors of genitourinary function and robotic surgery.Between January 2017 and January 2020, patients with rectal cancer (cT1-3NxM0) were registered. Genitourinary function was assessed by the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) test, Female Sexual Function Index (FSFI) and urodynamic examination before surgery and 1, 3, 6, and 12 months postoperatively. Genitourinary function was compared between the laparoscopic total mesorectal excision (L-TME) and robotic total mesorectal excision (R-TME) groups, and the correlative factors associated with postoperative genitourinary function were analysed using the generalized estimated equation (GEE).Compared with L-TME, R-TME showed a superior IPSS, voiding volume, residual urine volume and IIEF score during the early postoperative period. According to the GEE analysis, postoperative genitourinary function was positively correlated with laparoscopic anterior resection/abdomen perineal resection (LAR/APR) but negatively correlated with tumour size, tumour distance to anus, TNM, adjuvant chemotherapy, adjuvant radiotherapy, complete TME, circumferential resection margin (CRM), blood loss, diverting stoma, conversion, and anastomotic leakage.Due to the important role of robotic surgical technology on the influential factors of postoperative genitourinary function and the superiority of identifying and preserving autonomic nerves, robotic technology is conducive to the early recovery of postoperative urogenital function while adhering to oncological dissection principles. No significant difference was found between the da Vinci R-TME and MicroHand R-TME groups.

Anlotinib as a third-line or beyond therapy for extensive-stage small-cell lung cancer (ES-SCLC) was studied. This single-arm phase II trial was to investigate the value of anlotinib plus platinum-etoposide as first-line treatment in ES SCLC.The primary endpoint was progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints included overall survival (OS), disease control rate (DCR), time to progression (TTP), duration of remission (DoR), and safety. The subgroups of preset liver metastasis and brain metastasis were analyzed.In 35 ES-SCLC patients, the median PFS, ORR, DCR, and OS were 8.02 months [95% confidence interval (CI): 6.90-9.66], 85.71% (95% CI: 69.74-95.19), 94.29% (95% CI: 80.84-99.30), and 15.87 months (95% CI: 10.38-18.89), respectively. The median PFS in the liver metastasis and brain metastasis subgroups was 7.33 months (95% CI: 4.76-9.69) and 7.34 months (95% CI: 5.68-9.20), respectively. The most common AEs with grade 3-4 were hand-foot syndrome (17%), granulocytosis (17%), stomatitis (14%), hypertriglyceridemia (11%), hypercholesterolemia (11%), as well as nausea and vomiting (11%), and no grade 5 AEs were recorded.Anlotinib combined with platinum-etoposide provided an effective and safe therapy for patients with ES-SCLC.

The purpose of this study was to investigate whether TXA can effectively reduce blood loss after HTO and related complications and to evaluate its safety.From March 2016 to March 2018, 100 patients who underwent medial opening wedge HTO in the Department of Orthopedics, the second affiliated hospital of xi'an jiaotong university, with an average age of 52.8 ± 3.2 years, were randomly divided into the TXA group (using intravenous TXA) and the control group (using the same amount of normal saline), with 50 patients in each group. The postoperative wound drainage volume, decrease in hemoglobin and hematocrit value, total blood loss, wound healing, blood transfusion, deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared between the two groups.The drainage volume on the first postoperative day and the total drainage volume of the TXA group were significantly lower compared with those of the control group (145.7 vs 264.5 ml, 282.3 vs 413.2 ml, P 0.05). The decreases in the hemoglobin and hematocrit values on the postoperative first, second and fifth days were lower in the TXA group than those in the control group (1.4 VS 3.5, 2.6 vs 3.3, 1.9 vs 2.9 g, P 0.05; 3.3 vs 5.5, 5.0 vs 9.1, 3.8 vs 7.2%, P 0.05), and the mean total blood loss was also lower in the TXA group than that in the control group (477.9 vs 834.6 ml, P 0.05). In the control group, 1 patient had wound hematoma requiring additional paracentesis and pressure dressing, 1 patient had superficial wound infection requiring additional debridement, and 1 patient had postoperative blood transfusion compared to none in the TXA group (P 0.05). There was no symptomatic DVT or PE in either of the groups.Intravenous TXA can effectively and safely reduce blood loss and bleeding-related complications after HTO and was beneficial for the blood management of HTO.

Background and objective Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes. Methods We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib, " "lung cancer, " and "fistula." Results Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophago-tracheobronchial fistula. Six patients all died within 6 months. Conclusion Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.

Introduction: Ultrasound-guided thoracic paravertebral block (US-TPVB) is generally used for postoperative analgesia. We hypothesized that single-injection US-TPVB could be used as the principal anesthetic technique for a peritoneal dialysis catheter (PDC) procedure (implantation or removal). The anesthetic effect and venous ropivacaine level after a TPVB would be compared with that after local anesthetic infiltration (LAI). Methods: Patients undergoing PDC procedures were randomized into Group LAI or TPVB. In Group LAI, 40 mL of 0.25% ropivacaine were used. In Group TPVB, single-injection of US-TPVB at T10–T11 level was performed with 20 mL of 0.25% ropivacaine. The quality of anesthesia, visual analogue scale of pain, and venous total plasma ropivacaine level were compared between the 2 groups. Results: Seventy-four eligible patients were enrolled and 38 in Group TPVB. Thirty patients in Group TPVB and 26 patients in Group LAI underwent PDC procedures successfully. Higher satisfaction rates by nephrologists and patients (76.3 and 78.9%) were reported in Group TPVB (44.4 and 44.4% in Group LAI, respectively). The peak venous total plasma ropivacaine concentrations were below the reported toxic threshold in the 2 groups. Conclusions: A single-injection US-TPVB with 20 mL of 0.25% ropivacaine at T10–T11 could be the principal anesthetic technique for PDC procedures, which provided a comparable anesthetic effect to that of LAI with 40 mL ropivacaine. Higher satisfaction rates by nephrologists and patients were observed in Group TPVB. The 20 mL dose of 0.25% ropivacaine used for an US-TPVB was safe in end-stage renal diseases patients.

A multicenter, observational cohort study was conducted in 10 hospitals in China. Patients diagnosed with PCP were included, and their baseline clinical characteristics were collected. A Boruta analysis was performed to identify potentially important clinical features associated with the use of IMV during hospitalization. Selected variables were further analyzed using univariate and multivariable logistic regression. A logistic regression model was established based on independent risk factors for IMV and visualized using a nomogram.In total, 103 patients comprised the training cohort for model development, and 45 comprised the validation cohort to confirm the model's performance. No significant differences were observed in baseline clinical characteristics between the training and validation cohorts. Boruta analysis identified eight clinical features associated with IMV, three of which were further confirmed to be independent risk factors for IMV, including age (odds ratio [OR] 2.615 [95% confidence interval (CI) 1.110-6.159];The nomogram demonstrated accurate prediction of IMV in patients with PCP. Clinical application of this model enables early identification of patients with PCP who require IMV, which, in turn, may lead to rational therapeutic choices and improved clinical outcomes.

Objective. To investigate the effect of a home care model on coping style and quality of life of patients with postcranial surgery complicated by epilepsy. Methods. One hundred and forty-four patients with postcranial surgery complicated by epilepsy admitted to our hospital from July 2017 to April 2018 were selected as study subjects and randomly divided into 63 cases each in the observation group and the control group. The control group was given nursing interventions including health education, psychological intervention, medication guidance, complication prevention, and follow-up management, while the observation group was jointly given collaborative family nursing interventions. At a follow-up of 6 months, indicators such as coping style, treatment compliance, and quality of life were compared between the two groups. Results. Patients in the observation group had significantly higher problem solving, help seeking, and rationalization scores and significantly lower self-blame scores than the control group ( P < 0.01 ); significantly higher treatment compliance than the control group ( P < 0.01 ); and significantly higher social functioning, emotional well-being, and energy/fatigue scores than the control group ( P < 0.01 ). Conclusion. The home care model helps to promote the development of positive coping styles, improve treatment compliance, and improve the quality of life of patients after cranial surgery.

Jin-Ping Zheng,1,* Jing Zhang,2,* Li-Jun Ma,3 Ping Chen,4 Mao Huang,5 Xue-Mei Ou,6 Zi-Wen Zhao,7 Shu-Juan Jiang,8 Jie Cao,9 Wanzhen Yao2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Henan Provincial People’s Hospital, Henan, People’s Republic of China; 4Department of Internal Medicine, The Second Xiangya Hospital, Hunan, People’s Republic of China; 5Jiangsu Province Hospital, Jiangsu, People’s Republic of China; 6Department of Respiratory Medicine, West China Hospital, Chengdu, People’s Republic of China; 7Department of Respiratory Medicine, Guangzhou First People’s Hospital, Guangzhou, People’s Republic of China; 8Department of Respiratory Medicine, Shandong Provincial Hospital, Shandong, People’s Republic of China; 9Department of Respiratory Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wanzhen YaoDepartment of Respiratory Medicine, Peking University Third Hospital, 49 North Garden Road, Beijing 100191, People’s Republic of ChinaTel +86 156 1190 8216Email yaowanzhen11@edusbm.comPurpose: The current guidelines recommend the use of systemic corticosteroids (SCS) as the optimal treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this real-world study was to evaluate whether nebulized budesonide (NBS) could also be used as an initial treatment for AECOPD.Patients and methods: AECOPD patients initially treated with NBS or SCS (oral/intravenous) were enrolled. A large-scale, long-term multicenter cohort study of AECOPD patients was performed to analyze outcomes for each treatment (NCT02051166).Results: Initial NBS and SCS treatment resulted in similar outcomes in terms of improvements in FEV1, PaO2, SaO2, and PaCO2. Disease severity affected outcome similarly in both groups. When the groups were stratified according to whether the initial treatment was subsequently intensified or reduced, more intubation was seen in the groups in which initial treatment was intensified. NBS escalation and SCS reduction groups spent more days in the hospital. The NBS escalation group was associated with the highest medical expenditure and a relatively higher rate of new-onset pneumonia. The NBS maintenance/reduction group showed the lowest mortality rate between groups. Stratification according to initial PaCO2 level showed more intubation in the groups with high initial PaCO2 concentrations.Conclusion: These results indicate that NBS may be used as an initial treatment in certain AECOPD patients, and further studies are needed to better define those most likely to benefit.Keywords: nebulized budesonide, systemic corticosteroids, chronic obstructive pulmonary disease, AECOPD &nbsp

Background Asthma is associated with multiple psychiatric comorbidities. However, the relationship between asthma and suicidality has not be well established. Methods According to the PRISMA guidelines, protocol of the study was registered in the PROSPERO database (CRD42019123150). A systematic search of the PubMed, Embase and PsycINFO databases was performed for relevant studies published from its inception to January 25, 2019. Studies that reported the risk of suicidal ideation, attempts and mortality in asthmatics compared with non-asthmatics were included. A random-effects model was used to synthesize the estimates and the quality of the included studies was assessed under the Newcastle-Ottawa Scale. Results Twenty-eight studies including 2,759,841 asthmatic patients and 16,290,362 non-asthmatic controls were pooled and analyzed in the current study. The pooled data showed that asthmatic patients had increased risk of exhibiting suicidal ideation (OR, 1.52; 95%CI, 1.37–1.70), suicide attempts (OR, 1.60; 95%CI, 1.33–1.92) and suicide mortality (OR, 1.31; 95%CI, 1.11–1.55) compared to non-asthmatic controls. Noticeably, adolescent asthmatic patients had a more than 2-fold risk of suicide mortality compared to non-asthmatic controls (OR, 2.14; 95%CI, 1.61–2.83). Limitations The limitations of the present study were variability in study designs and various measures of asthma and suicidality, which possibly contribute to notable heterogeneity. Conclusions Patients with asthma have a significantly increased risk of suicidal ideation, suicide attempts and suicide mortality. Clinical physicians should pay more attention to the increased risk of suicidality in asthmatics, screen for these suicidal thoughts and behaviors, and make appropriate mental health referrals when necessary.

Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC). In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin. A highly significant association between a low Immunoscore and a shortened patient survival (P

Worldwide, the most prevalent metabolic disorder is diabetes mellitus (DM), an important condition that has been widely studied. Diabetic peripheral neuropathy (DPN), a complication that can occur with DM, is associated with pain and can result in foot ulcers and even amputation. DPN treatments are limited and mainly focus on pain management. There is a clear need to develop treatments for DPN at all stages. To make this progress, it is necessary to understand the molecular signaling pathways related to DPN. For this review, we aimed to concentrate on the main signaling cascades that contribute to DPN. In addition, we provide information with regard to treatments that are being explored.

Background Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results The sarcopenic group was significantly older (72.05 ± 6.54 years; P 11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P

Farnesoid X receptor (FXR) is a nuclear receptor that has emerged as a key regulator in the maintenance of hepatic steatosis, inflammation, and fibrosis. However, the role of FXR in renal fibrosis remains to be established. Here, we investigate the effects of the FXR agonist EDP‐305 in a mouse model of tubulointerstitial fibrosis via unilateral ureteral obstruction (UUO). Male C57Bl/6 mice received a UUO on their left kidney. On postoperative d 4, mice received daily treatment by oral gavage with either vehicle control (0.5% methylcellulose) or 10 or 30 mg/kg EDP‐305. All animals were euthanized on postoperative d 12. EDP‐305 dose‐dependently decreased macrophage infiltration as measured by the F4/80 staining area and proinflammatory cytokine gene expression. EDP‐305 also dose‐dependently reduced interstitial fibrosis as assessed by morphometric quantification of the collagen proportional area and kidney hydroxyproline levels. Finally, yes‐associated protein (YAP) activation, a major driver of fibrosis, increased after UUO injury and was diminished by EDP‐305 treatment. Consistently, EDP‐305 decreased TGF‐β1—induced YAP nuclear localization in human kidney 2 cells by increasing inhibitory YAP phosphorylation. YAP inhibition may be a novel antifibrotic mechanism of FXR agonism, and EDP‐305 could be used to treat renal fibrosis.—Li, S., Ghoshal, S., Sojoodi, M., Arora, G., Masia, R., Erstad, D. J., Ferriera, D. S., Li, Y., Wang, G., Lanuti, M., Caravan, P., Or, Y. S., Jiang, L.‐J., Tanabe, K. K., Fuchs, B. C. The farnesoid X receptor agonist EDP‐305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction. FASEB J. 33, 7103–7112 (2019). www.fasebj.org

Background Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibrosis is poorly understood. Methods miR-4739 levels were detected by miRNA array and real-time PCR. Real-time PCR, western blotting and immunofluorescence were used to identify the expression profile of indicators related to fibrosis. Target gene of miR-4739 and promoter activity assay was measured by using dual-luciferase reporter assay system. In vivo, pleural fibrosis was evaluated by Masson staining and miR-4739 level was detected by In situ hybridization histochemistry. Findings We found that bleomycin induced up-regulation of miR-4739 in pleural mesothelial cells (PMCs). Over-regulated miR-4739 mediated mesothelial-mesenchymal transition and increased collagen-I synthesis in PMCs. Investigation on the clinical specimens revealed that high levels of miR-4739 and low levels of bone morphogenetic protein 7 (BMP-7) associated with pleural fibrosis in patients. Then we next identified that miR-4739 targeted and down-regulated BMP-7 which further resulted in unbalance between Smad1/5/9 and Smad2/3 signaling. Lastly, in vivo studies revealed that miR-4739 over-expression induced pleural fibrosis, and exogenous BMP-7 prevented pleural fibrosis in mice. Interpretation Our data indicated that miR-4739 targets BMP-7 which mediates pleural fibrosis. The miR-4739/BMP-7 axis is a promising therapeutic target for the disease. Fund The National Natural Science Foundation of China.

Purpose There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. Materials and methods Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. Results Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. Conclusions EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.

Lung adenocarcinoma is the leading cause of tumor-related death. The tumor microenvironment (TME) may determine anti-tumor treatment responses. We focused on 23 m6A regulators, and analyzed m6A regulator expression patterns in 995 lung adenocarcinoma samples collected from 7 publicly available datasets. Two m6A clusters were identified, wherein gene clusters and m6A score were generated using unsupervised clustering and principal component analysis based on differentially expressed genes with prognostic significance. Further, three independent datasets from TCGA-LUAD and GEO were employed to validate the impact of m6A signatures and score. We found that m6A cluster 1 with high m6A score was associated with an inflamed TME, higher neoantigen and tumor mutation burden and improved response to immunotherapy. However, anti-tumor immunity cells were exhausted in high m6A score patients; thus, the prognosis of these patients was poor. Elucidation of m6A regulator expression pattern may facilitate the development of effective treatment strategies for lung adenocarcinoma.

PURPOSE To evaluate the value of α-fetoprotein (AFP) classification criteria in predicting tumor response and patient survival and to discuss the agreement between AFP criteria and modified Response Evaluation Criteria In Solid Tumors (mRECIST). MATERIALS AND METHODS Between January 2011 and December 2014, 147 patients with unresectable hepatocellular carcinoma (HCC) with baseline AFP levels ≥ 400 ng/mL who underwent transarterial chemoembolization as initial treatment were retrospectively enrolled for AFP/imaging correlation analysis. AFP-based response was classified as complete response (CR) in cases of AFP level normalization, partial response (PR) in cases of > 50% decrease vs baseline, stable disease (SD) in cases of -50% to +30% change vs baseline, or progressive disease (PD) in cases of > 30% increase vs baseline. Intermethod agreement between the 2 methods was assessed by Cohen κ coefficient. Response rates according to AFP and mRECIST were compared, and the association between response rate and overall survival (OS) was evaluated. RESULTS The κ value for agreement between AFP criteria and mRECIST was 0.549 (ie, moderate), with objective response and disease control rates of 36.1% and 63.3% per AFP criteria and 34.7% and 46.3% per RECIST (P = .807 and P = .003), respectively. Although AFP criteria and mRECIST showed significantly prognostic strata for CR, PR, SD, and PD after chemoembolization (P < .001 for both), some overlap in radiologic PD survival curves was observed. The OS of AFP-based disease control (ie, CR/PR/SD) was significantly longer than that of AFP-based PD among patients with radiologic PD (9.0 vs 6.0 mo; P < .001). CONCLUSIONS The defined AFP response moderately correlated with mRECIST response and yielded accurate prognostic prediction in patients with HCC and AFP levels ≥ 400 ng/mL treated with chemoembolization.

Objective This study aimed to evaluate the difference of two various robotic technology applied in R- Total mesorectal excision (TME). Methods From May 2017 to December 2018, consecutive patients with rectal cancer who underwent da Vinci R-TME or Micro Hand S R-TME were enrolled. The comparative study was conducted on Short-term Operative, Oncological, and Functional Outcomes between two type of R-TME. Results 47 patients underwent da Vinci R-TME, and 43 patients underwent Micro Hand S R-TME. No difference occured between two groups in TME completeness, CRM, DRM, CRM involvement and DRM involvement, operative time, blood loss, protective ileostomy, conversion rate, number of retrieved lymph nodes, Comprehensive Complication Index (CCI), International Prostate Symptom Score (IPSS) or Wexner scores. However, the setup time in the Micro Hand S group was longer. Conclusions In the present study, both da Vinci R-TME and Micro Hand S R-TME achieve excellent TME quality with acceptable morbidity and postoperative function.

Background Previous study indicated that transversus abdominis plane (TAP) block could be the principal anesthetic technique for peritoneal dialysis catheter (PDC) implantations. However, a TAP block could not provide an optimal anesthetic effect on catheter exit site during PDC implantation. We hypothesized that single-injection ultrasound-guided thoracic paravertebral block (US-TPVB) could be the principal anesthetic technique with better pain relief at catheter exit site during PDC implantation, compared to a TAP block. And anesthesia quality of a single-injection US-TPVB was compared with that of a TAP block and local anesthetic infiltration (LAI). Methods Patients undergoing PDC implantations were randomized into groups TPVB or TAP or LAI. In group TPVB, single-injection US-TPVB at T10-T11 level was performed with 20 ml of 0.25% ropivacaine. In group TAP, oblique subcostal TAP block was performed with 20 ml of 0.25% ropivacaine. In group LAI, 40 ml of 0.25% ropivacaine was used. Anesthesia quality was compared among the three groups, including general anesthesia conversion rate, cumulative rescuing sufentanil consumption, and satisfaction rate by nephrologists and patients. Results Eighty-eight eligible patients were enrolled. Visual analogue scale (VAS) at most time points (except for the catheter exit site) were lower in group TAP, compared with group TPVB. VAS at parietal peritoneum manipulation was 6 (5, 7), 3 (0, 6), and 7 (4.75, 9) in groups TPVB, TAP, and LAI, respectively (P P = 0.005). Lower general anesthesia conversion rate, less cumulative rescuing sufentanil consumption, and higher satisfaction rates by nephrologists and patients were recorded in group TAP, compared with groups TPVB and LAI. Conclusions Single-injection US-TPVB provided a better pain relief at catheter exit site. The quality and reliability of anesthesia after a single-injection US-TPVB was comparable to that of LAI, but not better than that of an oblique subcostal TAP block for PDC implantation. Trial registration TCTR20160911002. Registered on 8 September 2016.

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. No study has focused on the characteristic of population-based cancer survival in Fujian, which is regarded as one of the high-risk areas of cancer in China. This study aims to analyze the 5-year relative survival of patients in Fujian Province using population-based cancer registry data. A total of 8 population-based registries in Fujian Province reported cancer cases diagnosed in 2012-2014. Relative survival was calculated as the ratio between observed survival and expected survival. The 5-year relative survival for all cancers combined was 36.19% and the age-standardized 5-year relative survival for all patients was 31.80%. Females had higher relative survival than males (38.90% and 27.00%). The patients in urban areas had higher relative survival than those in rural areas (32.34% and 31.29%). Lung, gastric, liver, colorectal, and esophageal cancers were the five most common cancers, with 5-year relative survival below 50%. This is the first study that evaluated the population-based cancer relative survival in Fujian, China. Our study suggests that the overall survival of cancer patients in Fujian Province is poor. Furthermore, the results of this study can be used as a baseline for further research in Fujian, and provide important evidence for cancer etiology research.

To understand the potential role of soil seed bank in natural vegetation restoration of本文研究了杨树清理1、2年后迹地的土壤种子库结构、多样性及其与地上植被和土壤因子的关系,并以未清理杨树洲滩为对照,探讨洞庭湖杨树清理迹地土壤种子库在植被自然恢复中的潜力。结果表明: 研究样地土壤种子库萌发出的植物种子分属23科59属65种,各样地土壤种子库密度和物种数大小为:1年迹地(11810粒·m

Objective To evaluate the impact of robotic technology on the learning curve for robot-assisted gastrectomy in the initial clinical application stage and to compare RAG with laparoscopic-assisted gastrectomy using a short-term evaluation. Methods Between September 2016 and December 2018, 111 consecutive distal gastric cancer patients who were candidates for RAG or LAG were prospectively enrolled. Operative findings, morbidity, oncological findings, and the learning curve were analyzed. Results Thirty patients underwent RAG with the da Vinci Si robot system, and eighty-one patients underwent LAG. Blood loss was lower during RAG than during LAG (133.80 ± 95.28 vs. 178.83 ± 98.37, P = 0.046). The operative time for RAG was significantly longer (304.45 ± 42.08 vs. 281.17 ± 32.69, P = 0.015). The number of retrieved lymph nodes (LNs) was greater (37.33 ± 8.25 vs. 32.78 ± 5.98, P = 0.003) with RAG. Notably, RAG had an advantage in the dissection of No. 9 and 11p LNs (3.56 ± 1.76 vs. 2.78 ± 1.30, P = 0.038; 2.48 ± 0.93 vs. 1.99 ± 0.84, P = 0.015, respectively). Severe complications were less frequent in the RAG group (7 (8.6%) vs. 1 (3.3%), P = 0.003). No significant differences in terms of postoperative recovery were found between the two groups. The learning curve for RAG showed that the cumulative sum value decreased from the 10th case, while it decreased from the 28th case in the LAG group. Conclusion By means of robotic technology, RAG is better than LAG for the dissection of No. 9 and 11p LNs and for the alleviation of surgical trauma, and the technique is learned more rapidly during the preliminary stage than the LAG technique.

Objective Hysterectomy is associated with severe postoperative pain. The relative efficacy of pregabalin compared with other treatments for post-hysterectomy pain is unclear. Methods We searched the PubMed, Cochrane Library, and Web of Science databases for studies that compared the use of pregabalin and placebo for reducing pain in patients undergoing hysterectomy. Results This meta-analysis showed that pregabalin had limited pain-relieving effects at 2, 6, 24, and 48 hours after hysterectomy compared with placebo. Pregabalin significantly reduced postoperative nausea and vomiting. However, there was no significant difference in postoperative sedation or visual disturbances between patients treated with pregabalin and placebo. Conclusions Pregabalin is not clinically superior to placebo in terms of reducing pain intensity and morphine consumption in patients undergoing hysterectomy. However, the limitations of this meta-analysis mean that more high-quality randomized controlled trials are necessary to verify our pooled results.

Objectives Our aim was to investigate the prevalence and predictive variables of sarcopenia. Methods We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. Results The prevalence of sarcopenia and sarcopenic obesity was 9.2%‐16.2% and 0.26%‐9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut‐off value for age was 71 years, which departs from the commonly accepted cut‐off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25‐hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. Conclusions Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants., Dysregulated circadian clock genes were associated with glioma grades and the IDH status. Prognostic model suggests circadian clock genes affect glioma progression. The GO and GSEA enrichment analysis suggested dysregulated circadian clock genes can affect glioma through interfering cell cycle and influencing immunocytes infiltration.

Ovarian cancer (OC) is a kind of common gynecological malignancy around the world. Mounting literatures have confirmed the implication of lncRNAs in the development of various cancers. Long non-coding RNA (LncRNA) BBOX1-AS1 has not been reported in most cancer types including OC. Presently, we aimed at exploring the function and regulatory mechanism of BBOX1-AS1 in OC. As a result, we demonstrated the extremely high BBOX1-AS1 expression in OC tissues and cells. BBOX1-AS1 silence inhibited OC progression by suppressing cell proliferation and promoting cell apoptosis. Importantly, BBOX1-AS1 was verified to bind to miR-361-3p, which presented a low expression trend in OC cells. Subsequently, PODXL was testified as the downstream target of miR-361-3p. Of note, BBOX1-AS1 positively regulated PODXL through their competition in binding with miR-361-3p. Furthermore, miR-361-3p inhibition facilitated the growth of BBOX1-AS1-deficient OC cells, while such facilitating effect was then counteracted in response to PODXL depletion. All the results above explained that BBOX1-AS1 was overexpressed in OC and that BBOX1-AS1 caused carcinogenic influences on OC cell growth via miR-361-3p/PODXL pathway, highlighting BBOX1-AS1 as a novel potential target for OC treatment.

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.

Background and objective Although the association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and chronic periodontitis (CP), chronic periodontitis with type 2 diabetes mellitus (DP) is assumed, results of this association have been contradictory. The aim of this study was to assess the relationship between rs1800629 polymorphism and CP/DP susceptibility. Methods We searched for studies on PubMed, Web of Science, MEDLINE, Chinese National Infrastructure, and WanFang databases. Study selection was performed using specific inclusion and exclusion criteria and fulfilled the PECO (participant, exposure, comparison, and outcome) format. The relationship between rs1800629 polymorphism and CP/DP susceptibility was evaluated by the effect summary odds ratio (OR) and 95% confidence intervals (CIs). Allele, dominant, and recessive genetic models were computed to assess the strength of the association. Results A total of 25 case-control studies were included in the analysis. In the Asian population, TNF-α rs1800629 polymorphism was found to be significantly associated with CP in the overall analyses and for all genetic contrasts, while no significant risks were found among Caucasian populations for all genetic contrasts. The TNF-α rs1800629 polymorphism was also associated with increased DP risk in Asians under the fixed-effects model, but not in the recessive comparison. Conclusion The meta-analysis suggested that TNF-α rs1800629 polymorphism might affect the risk of CP and DP, particularly in individuals of Asian descent.

Background Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop‐mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically. Methods Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS‐2 tool independently. I2 statistic and chi‐square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection. Results A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies. Conclusion Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection.

To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis.Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively.(1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P0.05), especially in those treated with shikonin.The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.

To explore the aesthetic effect of orthodontics treatment combined with periodontal splint in the treatment of fan-shaped displacement of anterior teeth caused by periodontitis.Fifty patients with fan-shaped displacement of anterior teeth caused by periodontitis in PLA air force hospital from January 2013 to October 2018 were selected and randomly divided into the control group (n=25) and the experimental group (n=25). Patients in the control group were treated with conventional periodontal splint, while patients in the experimental group were treated with combined orthodontic treatment on the basis of the control group. Florida periodontal probe exploration depth (PD), gingival index (GI), attachment loss (AL), sulcus bleeding index (SBI), plaque index (PLI) and mobility were observed and compared before and 1 month after treatment between both groups. The levels of serum inflammatory factors interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and osteocalcin (OC) were measured and compared by ELISA before treatment and 1 month after treatment in both 2 groups. The data were analyzed with SPSS 21.0 software package.Compared with before treatment, PD and GI in both groups decreased significantly after treatment, and significantly lower in the experimental group than that in the control group (P0.05); the levels of AL, SBI, PLI and tooth looseness in both 2 groups were significantly lower after treatment, and significantly lower in the experimental than in the control group (P0.05); compared with before treatment, the levels of IL-4, IL-6, TNF-a and serum CRP in both 2 groups were significantly lower after treatment, and the experimental group was much lower than that in the control group (P0.05). The level of osteocalcin in the experimental group was significantly higher than that in the control group at different time points after treatment (P0.05). The level of osteocalcin in the experimental group reached its peak one day after treatment, and then gradually declined, the preoperative level was basically restored 7 days after treatment.Using orthodontics combined with periodontal splint in the treatment of fan-shaped displacement of anterior teeth caused by periodontitis has a remarkable effect. The symptoms of periodontitis can be effectively improved, the teeth can be effectively corrected and facial profiles of the patients can be improved.

Solitary laryngeal neurofibromas are exceedingly rare with only 14 cases reported in the previous literature. Herein, we reported a case of solitary laryngeal neurofibroma and reviewed all the published cases of this disease on the clinical manifestations and management options. Patients with solitary laryngeal neurofibromas can present with a variety of respiratory symptoms. Immunohistochemical examination of tumor specimen is critical for pathologic diagnosis and complete surgical resection is the optimal therapy. Endoscopic microsurgeries followed by CO2 laser management of the surgical border may be effective on preventing recurrence. Depending on the location, size and invasiveness of the lesions, the management and prognosis vary among patients. Long-term follow-up is highlighted owing to the possibility of recurrence during a long period of time after surgery.

It has been reported that class I histone deacetylase (HDAC) inhibition increases thermogenesis in fat, but adipocyte-specific Hdac3 deletions have presented inconsistent results. In this study, we observed that HDAC3 protein levels were lower in brown fat compared with inguinal subcutaneous adipose tissue, and they decreased in both fat depots upon cold exposure. PR domain–containing 16 (PRDM16) physically interacted with HDAC3, and treatment with HDAC3-selective inhibitor RGFP966 induced thermogenic gene expression in murine and human fat cultures. This induction was blunted in the absence of PRDM16. Our results provide evidence that HDAC3 is involved in thermogenesis, suggesting selective inhibition of HDAC3 in brown and beige fat might hold therapeutic potential for counteracting human obesity and metabolic disorders.

Beige adipocytes have recently been shown to regulate energy dissipation when activated and help organisms defend against hypothermia and obesity. Prior reports indicate that beige-like adipocytes exist in adult humans and that they may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we found that expression of the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) was induced in subcutaneous fat during the activation of these cells and that acetylcholine-producing immune cells within this tissue regulated this signaling pathway via paracrine mechanisms. CHRNA2 functioned selectively in uncoupling protein 1 (Ucp1)-positive beige adipocytes, increasing thermogenesis through a cAMP- and protein kinase A-dependent pathway. Furthermore, this signaling via CHRNA2 was conserved and present in human subcutaneous adipocytes. Inactivation of Chrna2 in mice compromised the cold-induced thermogenic response selectively in subcutaneous fat and exacerbated high-fat diet-induced obesity and associated metabolic disorders, indicating that even partial loss of beige fat regulation in vivo had detrimental consequences. Our results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors in energy metabolism. These findings may lead to identification of therapeutic targets to counteract human obesity.

Background Alzheimer’s disease (AD) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. Transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into AD; the extent to which these animal models recapitulate AD-type neuropathology is an issue of importance. Putative C-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) family, have recently been shown to deposit in the neuritic β-amyloid (Aβ) plaques in the human brain. Methods We set out to explore if extracellular sortilin neuropathology exists in AD-related transgenic mice and nonhuman primates. Brains from different transgenic strains and ages developed overt cerebral Aβ deposition, including the β-amyloid precursor protein and presenilin 1 double-transgenic (APP/PS1) mice at ~ 14 months of age, the five familial Alzheimer’s disease mutations transgenic (5×FAD) mice at ~ 8 months, the triple-transgenic Alzheimer’s disease (3×Tg-AD) mice at ~ 22 months, and aged monkeys (Macaca mulatta and Macaca fascicularis) were examined. Brain samples from young transgenic mice, middle-aged/aged monkeys, and AD humans were used as negative and positive pathological controls. Results The C-terminal sortilin antibody, which labeled senile plaques in the AD human cerebral sections, did not display extracellular immunolabeling in the transgenic mouse or aged monkey brain sections with Aβ deposition. In Western blot analysis, sortilin fragments ~ 15 kDa were not detectable in transgenic mouse cortical lysates, but they occurred in control AD lysates. Conclusions In reference to their human brain counterparts, neuritic plaques seen in transgenic AD model mouse brains represent an incomplete form of this AD pathological hallmark. The species difference in neuritic plaque constituents also indicates more complex secondary proteopathies in the human brain relative to rodents and nonhuman primates during aging and in AD. Electronic supplementary material The online version of this article (10.1186/s13195-018-0370-2) contains supplementary material, which is available to authorized users.

Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and plays a key functional role in various cancer cells. Although MELK may not be a cancer addiction target, the development of specific MELK inhibitors would provide useful chemical tools for synthetic lethal investigation. Herein, we identified several hit compounds using a customized structure-based virtual screening, among which compounds 4 and 16 showed the most potent inhibition to MELK with IC50 values of 3.52 μM and 178.3 nM, respectively. In vitro cell-based assays revealed that 16 has no effect on the growth of various types of cancer cells, but has the potential to inhibit cancer cell migration and invasion. Western blotting analyses revealed that 16 suppresses the phosphorylation of focal adhesion kinase (FAK), a downstream molecule of MELK, which is a key kinase in regulating cancer cell migration and invasion.

Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment.Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans.CA significantly activated PKA signaling, increased expression levels of thermogenic genes and induced phosphorylation of HSL and PLIN1 in murine primary adipocytes. Inhibition of PKA or p38 MAPK enzymatic activity markedly inhibited the CA-induced thermogenic response. In addition, chronic CA treatment regulates metabolic reprogramming, which was partially diminished in FGF21KO adipocytes. Importantly, both acute and chronic effects of CA were observed in human adipose stem cells isolated from multiple donors of different ethnicities and ages and with a variety of body mass indexes (BMI).CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.