Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Objective:To explore the effects of the deep inspiration breath-hold (DIBH) technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy (IMN-IMRT) for postoperative left breast cancer.Methods:Totally 23 left breast cancer patients in the First Affiliated Hospital of Bengbu Medical College from Octorber 2021 to July 2022 receiving postoperative IMN-IMRT were enrolled in this study. The changes in dosimetric parameters for their heart and left anterior descending coronary artery (LAD) in the DIBH mode were observed, and the potential factors affecting DIBH effects were analyzed.Results:Compared with the free breath (FB) mode, the DIBH mode manifested a heart volume decrease by 18% ( t = 10.47, P < 0.001), a left lung volume increase by 42% ( t = -14.55, P < 0.001), and significantly reduced dosimetric parameters ( Dmean, Dmax, V5- V30) for the heart and LAD, exhibiting statistically significant differences ( t=-13.38 to -3.30, P<0.05). As indicated by the Pearson correlation analysis, the relative ratio of cardiac dose reduction was positively correlated with that of left lung expansion ( r = 0.82, P < 0.001) and negatively correlated with the patient′age ( r = -0.56, P = 0.005). Conclusions:DIBH can effectively reduce the heart and LAD radiation doses in IMN-IMRT for postoperative left breast cancer and that the patient's age, and the DIBH effects might be affected by the vital capacity.

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective: To explore the efficacy and feasibility of transanal hand-sewn reinforcement of low stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision (taTME). Methods: A descriptive cohort study was conducted. Clinical data of 51 patients with rectal cancer who underwent taTME with transanal hand-sewn reinforcement of low stapled anastomosis at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were retrospectively collected. Inclusion criteria: (1) age >18 years old; (2) rectal cancer confirmed by preoperative pathology; (3) distance from tumor to anal verge ≤ 8 cm according to pelvic MR; (4) the lesion was evaluated to be resectable before operation; (5) with or without neoadjuvant chemotherapy and radiotherapy; (6) taTME, end-to-end stapled anastomosis, and reinforcement in the anastomosis with absorbable thread intermittently were performed, and the distance between anastomosis and anal verge was ≤ 5 cm. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) emergency surgery due to intestinal obstruction, bleeding or perforation; (3) patients with local recurrence or distant metastasis; (4) the period of postoperative follow-up less than 3 months. The procedure of transanal hand-sewn reinforcement was as follows: firstly, no sign of bleeding was confirmed after checking the anastomosis. Then, the anastomosis was reinforced by suturing the muscle layer of rectum intermittently in a figure-of-eight manner using 3-0 single Vicryl. The entry site of the next suture was close next to the exit site of the last one. Any weak point of the anastomosis could also be reinforced according to the specimen from the circular stapler. The primary outcome were the incidence of anastomotic leak, methods of the secondary operation, anastomotic infection, anastomotic stricture, and conditions of Intraoperative and postoperative. Results: All the 51 enrolled patients completed surgery successfully without any conversion to open surgery. The median operative time was 169 (109-337) minutes, and the median intraoperative blood loss was 50 (10-600) ml. The median postoperative hospital stay was 8 (5-16) days. The mssorectum was complete and distal resection margin was negative in all patients. Postive circumferential resection margin was observed in 1 patients (2.0%). Twelve (23.5%) patients underwent prophylactic ileostomy. One patient developed anastomosis stricture which was cured by digital dilatation of the anastomosis. ISREC grade C anastomotic leak was observed in 3 (5.9%) male patients, of whom 2 cases did not received prophylactic ileostomy during the operation, and were cured by a second operation with the ileostomy and anastomotic repair. The other one healed by transanal repair of the anastomosis and anti-infection therapy. One (2.0%) patient suffered from perianal infection and healed by sitz bath and anti-infection therapy. No death was reported within 30 days after operation. Conclusion: Transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after taTME is safe and feasible.
Adolescent ; Anal Canal/surgery* ; Anastomosis, Surgical ; Anastomotic Leak/prevention & control* ; Cohort Studies ; Humans ; Laparoscopy ; Male ; Postoperative Complications/prevention & control* ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Retrospective Studies ; Treatment Outcome

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

In recent years, the impact of meteorological factors on health and injury has been paid more and more attention. Severe weather events were considered to be an important risk factor for traffic accident injuries. Evidence from a large number of epidemiological studies suggests that meteorological factors, including high temperatures, rainfall, snowfall, wind and visibility, might be related to the occurrence of traffic accidents. This systematic review attempts to summarize the current research status of meteorological factors on traffic accident injury, systematically review the relationship between meteorological factors and traffic accident injury, and discuss how to further carry out related research.

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.

Objective: To analyze the gene mutation spectrum, clinical features, and the factors of disease progression and prognosis in patients with essential thrombocytosis (ET) . Methods: A retrospective analysis was conducted on 178 newly diagnosed ET patients admitted from February 1st, 2009 to November 1st, 2018. Results: Of the 178 patients, 89 were male and 89 female, and the median diagnosis age was 49.5 (3-86) years old. JAK2V617F, CALR and MPL mutations frequencies were 16.45% (1.67%-43.90%) , 40.00% (10.00%-49.15%) and 25.10% (25.00%-40.00%) , respectively. Compared with patients with CALR mutations, patients with JAK2V617F mutation had higher diagnosis age (P=0.035) , higher white blood cell count (P=0.040) , higher hemoglobin concentration (P=0.001) , and lower platelet count (P=0.002) , respectively. Of them, 47 patients (27.01%) developed thrombotic events before diagnosis, and 3 ones (1.72%) experienced thrombotic events after diagnosis. Multivariate analysis revealed age >60 years (P=0.013, OR=4.595, 95%CI 1.382-15.282) and cardiovascular risk factors (CVF) (P<0.001, OR=8.873, 95%CI 2.921-26.955) as risk factors for thrombotic events, CALR mutation (P=0.032, OR=0.126, 95%CI 0.019-0.838) as a protective factor for thrombotic events. Age >60 years (P=0.042, OR=4.045, 95%CI 1.053-15.534) was found to be a risk factor for the overall survival (OS) of ET patients. OS of age ≤60 years and age>60 years were calculated by Kaplan-Meier analysis to be (115.231±1.899) months and (83.291±4.991) months (χ²=6.406, P=0.011) , respectively. Conclusion Age>60 years and CVF were risk factors for thrombotic event. CALR mutation was a protective factor for thrombotic event. Age >60 years was a risk factor for OS in ET patients.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.