Superior medical resources or geographic proximity? The joint effects of regional medical resource disparity, geographic distance, and cultural differences on online medical consultation.

Online medical consultation platforms enable patients to seek health advice from physicians across geographic regions. In this study, we analyze patterns of online consultation between patients and physicians. We examine the joint effects of regional medical resource disparity, geographic distance, and cultural differences between patients and physicians on patients' decisions about which physicians they consult online. Using a unique dataset of city-to-city tuples based on 813,684 online consultation records and combining it with region-level data from multiple external sources, we find that while regional medical resource disparity drives patients from medically disadvantaged regions to seek online consultations with physicians from medically advantaged regions, geographic distance and cultural differences tend to constrain these consultations. We also find that cultural differences can amplify the impact of regional medical resource disparity, whereas geographic distance may lessen this effect. Further, we discover that the constraining effect of geographic distance is partly due to the online-to-offline nature of online medical consultations. Moreover, additional analyses suggest that physicians' online reputation and information about physicians' participation on the platform can help alleviate the negative effects of geographic distance and cultural differences. These findings hold significant implications for the allocation of medical resources and the formulation of healthcare policies.

Modified Danggui Beimu Kushen Pills Inhibit Tumor Growth and Regulates T Cell Subsets in H22 Hepatocellular Carcinoma-bearing Mice / 中国实验方剂学杂志

ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model， cisplatin， low- （4 g·kg-1·d-1）， medium- （8 g·kg-1·d-1）， and high-dose （16 g·kg-1·d-1） modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days， the mice were sacrificed on day 15. The tumor volume was measured on days 0， 4， 8， 12， 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells， and the tumor cell-killing rate was detected by the cell counting kit-8 （CCK-8）. Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 （PD-1） and lymphocyte activation gene-3 （LAG-3） in spleen and tumor tissues. The number of CD4+ and CD8+ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry （IHC）. ResultOn day 8 of drug administration， tumor volumes in all treatment groups decreased compared with that in the model group. On day 15， both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group （P<0.01）， with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups， medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index （P<0.01）. Compared with the model group， all treatment groups showed increased spleen index （P<0.05， P<0.01）， with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups， all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4+ and CD8+ T cells and tumor cell-killing rate in the spleen and tumor tissues （P<0.01） and down-regulated mRNA and protein levels of LAG-3 （P<0.05， P<0.01）. The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups （P<0.01）. ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4+ and CD8+ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression， thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.

Thermal, photonic, and electrocatalysis in lignin depolymerization research.

In order to realize a sustainable bio-based future, it is essential to fully harness the potential of biomass, including lignin - a readily available biopolymer that ranks second in abundance and serves as a renewable source of aromatics. While lignin has traditionally been used for lower-value applications like fuel and power generation, unlocking its higher-value potential through diverse conversion and upgrading techniques is of paramount importance. This review focuses on the catalytic conversion of lignin, with a specific emphasis on selective depolymerization, a process that not only supports economically and environmentally sustainable biorefineries but also aligns with Green Chemistry principles, mitigating adverse environmental impacts. Furthermore, we provide a comprehensive discussion of reaction pathways and mechanisms, including C-O and C-C bond cleavage, among different catalysts. Lastly, we analyze and briefly discuss the prospects of rational catalyst design in biomass valorization.

Effects of SIRT1 on morphine-induced conditioned place preference in rats through CREB/BDNF pathway / 中国药理学通报

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

Characteristics of intestinal flora in patients with cerebral infarction complicated with Type 2 diabetes mellitus / 中南大学学报(医学版)

OBJECTIVES@#The intestinal microbial characteristics of patients with simple cerebral infarction (CI) and CI complicated with Type 2 diabetes mellitus (CI-T2DM) are still not clear. This study aims to analyze the differences in the variable characteristics of intestinal flora between patients simply with CI and CI-T2DM.@*METHODS@#This study retrospectively collected the patients who were admitted to the Affiliated Hospital of Putian University from September 2021 to September 2022. The patients were divided into a CI group (n=12) and a CI-T2DM group (n=12). Simultaneously, 12 healthy people were selected as a control group. Total DNA was extracted from feces specimens. Illumina Novaseq sequencing platform was used for metagenomic sequencing. The Knead Data software, Kraken2 software, and Bracken software were applied for sequencing analysis.@*RESULTS@#At phylum level, the average ratio of Firmicutes, Bacteroidetes, and Proteobacteria in the CI-T2DM group were 33.07%, 54.80%, and 7.00%, respectively. In the CI group, the ratios of each were 14.03%, 69.62%, and 11.13%, respectively, while in the control group, the ratios were 50.99%, 37.67%, and 5.24%, respectively. There was significant differences in the distribution of Firmicutes (F=6.130, P=0.011) among the 3 groups. At the family level, compared with the CI group, the relative abundance of Eubacteriaceae (t=8.062, P<0.001) in the CI-T2DM group was significantly increased, while Corynebacteriaceae (t=4.471, P<0.001), Methanobacteriaceae (t=3.406, P=0.003), and Pseudomonadaceae (t=2.352, P=0.028) were decreased significantly. At the genus level, compared with the CI group, there was a relative abundance of Cutibacterium (t=6.242, P<0.001), Eubacterium (t=8.448, P<0.001), and Blautia (t=3.442, P=0.002) in the CI-T2DM group which was significantly increased. In terms of Methanobrevibacter (t=3.466, P=0.002), Pyramidobacter (t=2.846, P=0.009) and Pseudomonas (t=2.352, P=0.028), their distributions were decreased significantly in the CI-T2DM group. At the species level, compared with the CI group, the relative abundance of Cutibacterium acnes (t=6.242, P<0.001) in the CI-T2DM group was significantly increased, while Pseudomonas aeruginosa (t=2.352, P=0.028) was decreased significantly. Still at the genus level, linear discriminant analysis effect size (LEfSe) analysis showed that the distributions of Pseudomonas and Blautia were determined to be the most significantly different between the CI-T2DM and the CI group. At the species level, the total number of operational taxonomic units (OTUs) in the 3 groups was 1 491. There were 169, 221, and 192 kinds of OTUs unique to the CI-T2DM, CI, and control group, respectively.@*CONCLUSIONS@#From phylum level to species level, the composition of intestinal flora in the patients with CI-T2DM is different from those in the patients simply with CI. The change in the proportion of Firmicutes, Bacteroidetes and Proteus compared with the healthy population is an important feature of intestinal flora imbalance in the patients with CI and with CI-T2DM. Attention should be paid to the differential distribution of Bacteroides monocytogenes and butyrate producing bacteria.

Six novel minimally invasive therapies for benign prostatic hyperplasia / 浙江大学学报·医学版

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in men. When drug treatment is ineffective or conventional surgery is not suitable, novel minimally invasive therapies can be considered. These include prostatic urethral lift, prostatic artery embolisation, water vapor thermal therapy, Aquablation-image guided robotic waterjet ablation, temporary implantable nitinol device and prostatic stents. These novel therapies can be performed in outpatient setting under local anesthesia, with shorter operative and recovery times, and better protection of ejaculatory function and erectile function. General conditions of the patient and advantages and disadvantages of the each of these therapies should be fully considered to make individualized plans.

Application value of CT examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.

Application value of CT examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.

A propensity score matching study on safety and efficacy of laparoscopic cholecystectomy for T2a and lower stages of gallbladder carcinoma / 中华肝胆外科杂志

Objective:To study the safety and efficacy of laparoscopic cholecystectomy (LC) in treatment of T2a and lower stages of gallbladder carcinoma.Methods:A retrospective study was performed on patients who were diagnosed with gallbladder cancer and underwent surgical treatment from January 2016 to January 2021 at Hunan Provincial People's Hospital. These patients were divided into the simple treatment group and the radical treatment group based on the surgical methods used. The simple treatment group consisted of 64 patients who underwent LC for accidental gallbladder cancers. The radical treatment group consisted of 30 patients who underwent laparoscopic radical cholecystectomy (LRC). The baseline characteristic of the two groups of patients were matched in a 1∶1 ratio using propensity score matching. After matching, there were 26 patients in each of the 2 groups. There were 7 males and 19 females in the simple group, with mean ± s. d. age of (60.6±9.6) years. There were 8 males and 18 females, with mean ± s. d. age (60.9±9.1) years in the radical treatment group. Blood loss, operation time, postoperative hospital stay, biliary leakage, acute pulmonary embolism, and incisional infection were compared between the two groups.Results:In the simple group, the operative time was (78.7±62.9) min, intraoperative blood loss was (10.7±11.6) ml and postoperative hospital stay was (4.4±2.6) d. These results were significantly better than those in the radical group with operative time (298.7±101.3) min, intraoperative blood loss (161.9±96.7) ml and postoperative hospital stay (9.9±4.0) d (all P<0.05). There were no significant difference in the postoperative complications and disease free survival rates between the two groups (both P>0.05). Conclusion:LC was safe and effective for treatment of T2a and lower stages of gallbladder cancer, and it could achieve a similar disease-free survival rate as LRC.

Low temperature exposure increases IL-6 expression in skeletal muscle cells / 生理学报

The shivering and nonshivering thermogenesis in skeletal muscles is important for maintaining body temperature in a cold environment. In addition to nervous-humoral regulation, adipose tissue was demonstrated to directly respond to cold in a cell-autonomous manner to produce heat. However, whether skeletal muscle can directly respond to low temperature in an autoregulatory manner is unknown. Transient receptor potential (TRP) channels TRPM8 and TRPA1 are two important cold sensors. In the current study, we found TRPM8 was expressed in mouse skeletal muscle tissue and C2C12 myotubes by RT-PCR. After exposure to 33 °C for 6 h, the gene expression pattern of C2C12 myotubes was significantly changed which was evidenced by RNA-sequencing. KEGG-Pathway enrichment analysis of these differentially expressed genes showed that low temperature changed several important signaling pathways, such as IL-17, TNFα, MAPK, FoxO, Hedgehog, Hippo, Toll-like receptor, Notch, and Wnt signaling pathways. Protein-protein interaction network analysis revealed that IL-6 gene was a key gene which was directly affected by low temperature in skeletal muscle cells. In addition, both mRNA and protein levels of IL-6 were increased by 33 °C exposure in C2C12 myotubes. In conclusion, our findings demonstrated that skeletal muscle cells could directly respond to low temperature, characterized by upregulated expression of IL-6 in skeletal muscle cells.

Serine protease inhibitor Hespintor’s potential mechanism based on integrated transcriptomics in inhibiting the growth of transplanted hepatoma in nude mice / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship between differential expressions of lncRNAs and mRNAs and Hespintor’s possible anti-tumor mechanism using transcriptome sequencing technology. 【Methods】 First， a nude mouse model of human hepatoma tumors was established. The tumor tissue mass was collected after 4 weeks of group treatment. The cDNA libraries of tumor tissues were established in the Hespintor treatment group and the solvent control group， and transcriptome sequencing was performed. Based on RNA-seq data， the differentially expressed lncRNA and mRNA genes were screened， and the functional enrichment and interaction analysis were performed. The network module division approach was utilized to identify the target genes of Hespintor and build its regulatory network. 【Results】 The Hespintor treatment group yielded a high-confidence differentially expressed gene collection of 2 003 lncRNAs （DEGs lncRNA） and 1 038 mRNAs （DEGs mRNA）. Target mRNAs regulated by DEGs lncRNA were mainly enriched in PIP3 to activate the Akt signal， p53 signal pathway， FOXO-mediated transcription， and cell cycle， among other things. DEGs mRNA were primarily enriched in chemokine signaling pathways， extracellular matrix receptor interactions， complement， and coagulation cascades. Both of them were related in three ways： cell behavior， transcriptional regulation， and cell cycle. 【Conclusion】 The PI3K/Akt signaling pathway may play a key role in the inhibitory effect of Hespintor on tumor， inducing G1/S phase cell cycle arrest and apoptosis.

Characterization of bat coronaviruses: a latent global threat

It has been speculated that bats serve as reservoirs of a huge variety of emerging coronaviruses (CoVs) that have been responsible for severe havoc in human health systems as well as negatively affecting human economic and social systems. A prime example is the currently active severe acute respiratory syndrome (SARS)-CoV2, which presumably originated from bats, demonstrating that the risk of a new outbreak of bat coronavirus is always latent. Therefore, an in-depth investigation to better comprehend bat CoVs has become an important issue within the international community, a group that aims to attenuate the consequences of future outbreaks. In this review, we present a concise introduction to CoVs found in bats and discuss their distribution in Southeast Asia. We also discuss the unique adaptation features in bats that confer the ability to be a potential coronavirus reservoir. In addition, we review the bat coronavirus-linked diseases that have emerged in the last two decades. Finally, we propose key factors helpful in the prediction of a novel coronavirus outbreak and present the most recent methods used to forecast an evolving outbreak.

Characterization of bat coronaviruses: a latent global threat

It has been speculated that bats serve as reservoirs of a huge variety of emerging coronaviruses (CoVs) that have been responsible for severe havoc in human health systems as well as negatively affecting human economic and social systems. A prime example is the currently active severe acute respiratory syndrome (SARS)-CoV2, which presumably originated from bats, demonstrating that the risk of a new outbreak of bat coronavirus is always latent. Therefore, an in-depth investigation to better comprehend bat CoVs has become an important issue within the international community, a group that aims to attenuate the consequences of future outbreaks. In this review, we present a concise introduction to CoVs found in bats and discuss their distribution in Southeast Asia. We also discuss the unique adaptation features in bats that confer the ability to be a potential coronavirus reservoir. In addition, we review the bat coronavirus-linked diseases that have emerged in the last two decades. Finally, we propose key factors helpful in the prediction of a novel coronavirus outbreak and present the most recent methods used to forecast an evolving outbreak.

Efficacy and safety study of Chinese botulinum toxin A 100U in patients with overactive bladder: a prospective, multicenter, double-blind and randomized controlled trial / 中华泌尿外科杂志

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study

BackgroundThe 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. MethodsIn this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. ResultsOf the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. ConclusionsDiabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.

Comparative analysis of structural characteristics and epitopes in S proteins between SARS-CoV-2 and SARS-CoV / 浙江大学学报·医学版

OBJECTIVE@#To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV.@*METHODS@#Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed.@*RESULTS@#The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively.@*CONCLUSIONS@#The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.

Bmi-1-siRNA Regulates the Proliferation of K562 Leukemia Cells in vitro and in vivo by PTEN/pAKT Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Bmi-1 gene silence on the proliferation ability of K562 cells in vitro and in vivo, and to explore the relation of molecular mechanism between proliferation ability of K562 cells in vitro and in vivo with PTEN/pAKT signaling pathway.@*METHODS@#The Bmi-1 small interference RNA (siRNA) sequences were transfected into K562 cells for decreasing Bmi-1 expression. The effect of Bmi-1 siRNA on the proliferation of K562 cells in vitro and in vivo was detected by MTT method and colony-forming test, the effect of Bmi-1 siRNA on the tumorogenicity of K562 cells was observed by subcutaneous inoculation of K562 cells, LY294002 and Bpv treated K562 cells in nude mice, the expression of Bmi-1, PTEN and pAKT proteins were detected by Western blot.@*RESULTS@#The Bmi-1 siRNA could inhibit the proliferation activity, colony-forming and tumor-forming abilities of K562 cells. After the silence of Bmi-1 gene, the PTEN expression in Bmi-1 gene-silenced group was significantly enhanced. While the pAKT expression in Bmi-1 gene-silenced group was significantly reduced; after the K562 cells were treated with LY294002 (an inhibitor of pAKT), the pAKT expression colony-forming and tumor forming abilities were reduced in comparison with untreated K562 cells; after the K562-S1 cells were treated with Bpv (an inhibitor of PTEN), the PTEN expression decreased, while the pAKT expression, colony forming and tumor-forming abilities were restored.@*CONCLUSION@#The Bmi-1 gene possibly involves in regulation of K562 proliferation in vivo and in vitro, the effect of PTEN/pAKT signaling pathway maybe one of molecular mechanisms mediating this regulation.

The value of intravoxel incoherent motion diffusion weighted imaging in progressive muscular dystrophy / 西安交通大学学报(医学版)

Objective To explore the value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI ) in patients with progressive muscular dystrophy .Methods We enrolled 7 patients with known progressive muscular dystrophy (4 Becker muscle dystrophy ,BMD;3 limb-girdle muscle dystrophy ,LGMD) in this study .Both IVIM ,T1 WI and T2 STIR sequences were performed on both thighs of all the subjects .Slow ADC ,fast ADC and fraction of fast ADC (Ff ) were measured .Tl weighted images were used to assess the fat infiltration of their thigh muscles using a 0-5 modified version of Mercuri's scale .Slow ADC ,fast ADC and fraction of fast ADC (Ff) were compared among the fatty infiltration ,edematous muscle and unaffected muscle (neither edematous nor fatty infiltration muscles in patients ) .One-way analysis of variance was used for statistical analyses with a significance of P < 0 .05 . Results The mean slow ADC value of fatty infiltration . edematous muscle . and unaffected muscle was 0 .75+0.39,1 .14±0 .19,and 1.00±0 .11 (10 -3 mm2/s ) , respectively ( P < 0 .05 ) .The mean fast ADC value in the three groups was 7 .14±6 .51,13 .56±9 .67,and 4 .02±1.89 (10-3 mm2 /s ) , respectively (P< 0 .05 ) . There was no significant difference in the Ff values among the three groups ( P > 0 .05 ) .The mean slow ADC value in different grades of steatosis was 1 .00±0 .11, 0.98±0 .17, and 0 .50±0 .29 (10-3 mm2/s) , respectively ; the slow ADC value in heavy fat infiltration group differed significantly from that in the other two groups( P<0.05 ).Conclusion IVIM-DWI can be used to quantitatively evaluate the thigh diffusion and microcirculation characteristics of muscles in patients with PMD , make a quantitative analysis of edema and steatosis of the muscle .and reflect the degree of muscle steatosis .

The efficacy of transurethral enucleation of bladder tumor in the treatment of non muscle-invasive bladder cancer / 中国肿瘤临床

Objective: To evaluate the safety and efficacy of transurethral enucleation of bladder tumor(TUEBT) in the treatment of non muscle-invasive bladder cancer (NMIBC). Methods: The clinical and pathological data of 82 NMIBC patients treated between No-vember 2015 and January 2018 in the First Affiliated Hospital of the Jinzhou Medical University were retrospectively analyzed. The 82 NMIBC patients were divided into a TUEBT group (38 cases) and a transurethral resection of bladder tumor (TURBT) group (44 cases). The differences in intraoperative indices, postoperative indices, and pathological staging between the two groups were compared. Re-sults: The bladder irrigation, indwelling catheter, and postoperative hospitalization times in the TUEBT group were (21.00 ± 3.55) h, (4.34±0.81) d, and (5.29±0.96) d, respectively, compared with (27.57±3.87) h, (5.32±0.83) d, and (6.32±0.86) d in the TURBT group, and the differences between groups were statistically significant (P<0.05). The operative time in the TUEBT group [(29.55±4.13) min] was longer than in the TURBT group [(25.30±4.01) min]. The hemoglobin decrease in the TUEBT group [(2.00±0.38) g/dL] was less than that in the TURBT group [(2.30±0.32) g/dL]. The incidence of obturator nerve reflex in the TUEBT group was 13.16% (5/38), compared to 34.09% (15/44) in the TURBT group. The recurrence rate in the TUEBT group was 10.53% (4/38), compared to 29.55% (13/44) in the TURBT group. The detrusor deletion rate in the TUEBT group was 0 (0/38), compared to 31.82% (14/44) in the TURBT group. The re-peat transurethral resection (ReTUR) standard was met in 22 cases in the TUEBT group and 33 in the TURBT group. ReTUR due to lack of a detrusor was required in 0 cases in the TUEBT group and 14 in the TURBT group. The differences in the above clinical characteris-tics were statistically significant (P<0.05). Conclusions: TUEBT can remove a tumor completely, while preserving the detrusor, improv-ing the accuracy of pathological staging, and reducing the probability of ReTUR. For NMIBC, TUEBT can obtain satisfactory clinical effi-cacy, with surgical safety and long-term efficacy superior to those of TURBT.

Clinicopathologic analysis of prostatic cancer with single positive core biopsy after radical prostatectomy / 中华泌尿外科杂志

Objective To evaluate the clinical and pathological features of patients with prostate cancer who were diagnosed by single positive core biopsy and treated by radical prostatectomy (RP).Methods Between July 2012 and June 2016,164 patients with prostate cancer diagnosed by single positive core biopsy underwent RP.The mean age was 66.3 years old (ranged 41-82 years old),and the mean PSA level was 12.3 ng/ml (ranged 0.6-59.5 ng/ml).The biopsy Gleason score showed 6 scores in 113 cases,3 + 4 =7 scores in 21 cases,4 + 3 =7 scores in 18 cases,≥8 scores in 12 cases.Clinical stage was cT1 in 71 cases,cT2 in 92 cases,and cT3 in 1 case.The patients were divided into subgroups according to age,preoperative PSA level,biopsy Gleason score and clinical stage,and the pathological results were compared among these subgroups.Results Of the 164 patients,67 cases had Gleason score ≤ 6,52 cases Gleason score 3 + 4 =7,24 case Gleason score 4 + 3 =7,and 11 cases Gleason score ≥ 8.Ten patients had pT0 disease according to the RP specimen,3 had extraprostatic extensions,5 had seminal vesicle invasions,and 24 had positive surgical margins.Compared to the biopsy,the Gleason score of RP specimens was higher in 53 cases,concordant in 77 cases,and lower in 24 cases.There was no significant difference in the postoperative pathological features between the age group ＜ 70 years and the group ≥ 70 years.Compared with PSA ＜ 10 ng/ml,the likelihood of postoperative Gleason score ＞ 7 was significantly increased in PSA ≥10 ng/ml group [41.4％ (36/87) vs.66.2％ (51/77),P＜0.05].When the biopsy Gleason score was divided into four groups (6,3 + 4 =7,4 + 3 =7,≥ 8),there were significant differences in postoperative pathological stages among the four groups (P ＜ 0.05),and the patients with biopsy Gleason score 6 were more likely to have no residual cancer (stage T0) when compared with other Gleason scores [8.8％ (10/113) vs.0,P =0.09].The probability of no residual cancer in clinical T1 stage patients was significantly higher than that in T2 stage [11.3％ (8/71) vs.2.8％ (2/92),P =0.02],while the probability of Gleason score upgrading was significantly lower [23.9％ (17/71) vs.39.1％ (36/92),P ＜ 0.05].Conclusions Most single core prostate cancer have clinically significant disease.The treatment plan must be evaluated individually for patients with single core prostate cancer.