Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

Integrating genomics and transcriptomics to identify candidate genes for high-altitude adaptation and egg production in Nixi chicken.

1. This study combined genome-wide selection signal analysis with RNA-sequencing to identify candidate genes associated with high altitude adaptation and egg production performance in Nixi chickens (NXC).2. Based on the whole-genome data from 20 NXC (♂:10; ♀:10), the population selection signal was analysed by sliding window analysis. The selected genes were screened by combination with the population differentiation statistic (FST). The sequence diversity statistic (θπ). RNA-seq was performed on the ovarian tissues of NXC (n = 6) and Lohmann laying hens (n = 6) to analyse the differentially expressed genes (DEGs) between the two groups. The functional enrichment analysis of the selected genes and differentially expressed genes was performed.3. There were 742 genes under strong positive selection and 509 differentially expressed genes screened in NXC. Integrated analysis of the genome and transcriptome revealing 26 overlapping genes. The candidate genes for adaptation to a high-altitude environment, as well as for egg production, disease resistance, vision and pigmentation in NXC were preliminarily screened.4. The results provided theoretical guidance for further research on the genetic resource protection and utilisation of NXC.

[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

[Application of the Chinese Expert Consensus on Diabetes Classification in clinical practice].

Objective: To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification. Methods: Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC). Results: A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95%CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions: There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

[Free anterolateral femoral muscle flap and perforator flap transplantation for repair of the huge wound after periorbital tumor resection and orbital enucleation].

Objective: To observe the clinical effect of free anterolateral femoral muscle flap and perforator flap transplantation for repair of the huge wound and after periorbital tumor resection and orbital enucleation. Methods: It was a retrospective case series study. Twelve patients with orbital tumors admitted to the Department of Burn and Plastic Surgery of the Affiliated Hospital of Zunyi Medical University from February 2017 to April 2021 were included. There were 4 males and 8 females, aged 48 to 87 years. Nine patients had cutaneous squamous cell carcinoma, and 3 had basal cell carcinoma. All patients underwent extended resection of the tumor, resection of orbital contents and wound repair.All patients had the lesion completely removed, chimeric anterolateral thigh flap of the anterolateral femoral flap and perforator flap were transplanted to repair the wound. The donor area of the flaps was closed with tension sutures. The size of intraoperative resection lesion,intraoperative resection flap and muscle flap and the depth of the wound cavity were summarized. The postoperative flap survival, wound healing, surgical area appearance, flap color, thickness and texture, scarring and sensation in the surgical area, and tumor recurrence were observed. Results: The surgical procedures were successfully completed in all the 12 patients. The intraoperative resection lesion ranged from 7.0 cm × 5.0 cm to 15.0 cm × 8.0 cm. The depth of the wound cavity was 4.0 to 5.0 cm. The intraoperative resection flap range was 7.0 cm × 5.0 cm to 19.0 cm × 8.0 cm. The muscle flap size ranged from 4.0 cm × 3.0 cm to 5.0 cm × 4.0 cm. All flaps completely survived after surgery, and the wounds healed. The sutures at the recipient area were removed at 5 to 7 days after surgery, while the sutures at the donor area were removed at 12 to 14 days. All of the patients were followed up for 3 to 30 months. The scar at the periorbital area was concealed, and the color, thickness and texture of the flaps were similar to those of the surrounding normal skin. The scarring in the flap supply area was not hypertrophic, with localized decreased skin sensation around it. None of the patients had any tumor recurrence during the follow-up period. Conclusion: The anterolateral femoral muscle flap and perforator flap transplantation could efficiently repair the huge wound after orbital content removal, achieving satisfactory therapeutic effects.

[Seasonal variations influenced the semen quality of the sperm donor in Beijing area].

OBJECTIVE: To investigate the change trends of sperm quality with seasonal variations among the volunteers of sperm donors in Beijing area, as well as the relationship between two parameters. METHODS: Semen data from the volunteers of sperm donors in Human Sperm Bank of Peking University Third Hospital were collected using a retrospective study method. The subjects were divided into 4 seasonal groups based on the lunar solar terms and the time of sperm donation. The data were assessed to find whether there were differences in semen parameters among different seasonal groups, and to analyze the change trends and the influence of seasonal factors on semen parameters. RESULTS: A total of 21 174 semen parameter data were analyzed. Firstly, to analyze all data as a whole, in spring, summer, autumn and winter groups, sperm concentration was (106.04±59.67)×106/mL, (97.61±47.41)×106/mL, (100.18±47.17)×106/mL, (100.59±38.68)×106/mL, respectively, and the spring group was significantly higher than the other 3 seasonal groups (P < 0.001); proportion of progressive motility sperm (PR) was 56.49%±12.76%, 58.02%±13.65%, 58.05%±12.36%, and 57.66%±12.61%, respectively, spring group was lower than the other three seasonal groups, and summer group was better among the latter (P < 0.001). There was no difference in normal rate of sperm morphology among the four seasonal groups. The qualified rate of sperm donors in the winter group was higher than that in the other three seasons groups (P < 0.01), while the qualified rate in the summer group was lower than that in the other three seasons groups. In addition, the semen parameters of the volunteers during the screening period and the official sperm donation period were analyzed respectively, which revealed that sperm concentration of spring group was higher than that of summer and winter groups, and PR was lower than that of summer and autumn groups. On account of the semen parameters of official sperm donation period, multiple linear regression analysis found that season was the main factor affecting sperm concentration, the average sperm concentration in spring group was about 6×106/mL higher than in winter group, but PR was 2.9% lower in spring group compared with autumn group (all P < 0.05). CONCLUSION: Season was the influencing factor of semen quality of sperm donors in Beijing area. We recommend spring and winter may be the preferred seasons for sperm donation.

[The analysis to data from Chinese Rheumatism Data Center external quality assurance program for autoantibodies in 2021].

To evaluate the data obtained from the external quality assurance program initiated by Chinese Rheumatism Data Center (CRDC-QAP) for autoantibodies detection in 2021, so as to assess the consensus and differences in cross-laboratory testing to autoantibodies in China. This is a retrospective study. After collecting data from the first half year (from May 15th to July 10th) and the second half year (from August 15th to November 19th) of CRDC-QAP program for autoantibody detection in 2021, it firstly analyzed the qualitative consensus of the cross-laboratory results. Secondly, it compared the positivity grade of numeric results according to the Sample to cut-off ratio (S/CO ratio) calculation. Finally, the mean and coefficient variation (CV) of numeric results from three major manufacturers were calculated. A total of 303 and 332 clinical labs voluntarily participated in the first half year and the second half year of CRDC-QAP program for autoantibody detection in 2021, respectively. Except for anti-ß2 glycoprotein type I (aß2-GPI) IgM, the cross-laboratory consensus of qualitative results for the other autoantibodies is greater than 96%. As for anti-cyclic citrullinated peptide antibody (anti-CCP) and anti mitochondrial antibody-M2 (AMA-M2), the numeric results from more than 90% laboratories showed the same positivity grade. More than 50% of laboratories used chemiluminescence immunoassay (CLIA) for quantitative evaluation of autoantibody. The CV of numeric results from different manufacturers showed certain differences(P<0.01) with the range from 0 to 238%. Although high consensus can be observed in term of qualitative result for autoantibody detection in cross-laboratory, there are still certain differences in numeric results in term of positivity grade and manufacturer-based CV.

[MicroRNA 424-5p promotes the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting Kinesin family member 23].

Objective: To explore the effect of MicroRNA 424-5p/Kinesin family member 23(miR-424-5p/KIF23)axis on the malignant phenotype of hepatoma cells and its sensitivity of sorafenib. Methods: Real-time quantitative reverse PCR(qRT-PCR) and/or Western blot were used to detect the expression of miR-424-5p and KIF23 in liver cancer tissues and paracancerous tissues, human hepatocellular carcinoma(HCC) cells HepG2 and normal hepatocyte LO2. HepG2 cells transfected with miR-424-5p mimic and miR-424-5p mimic NC were respectively defined as miR-424-5p mimic group and mimic NC group, HepG2 cells transfected with KIF23 overexpression vector pcDNA3.1-KIF23 or empty vector pcDNA3.1 respectively were defined as OE-KIF23 group and Vector group, and HepG2 cells co-transfected with miR-424-5p mimic and overexpression vector pcDNA3.1-KIF23 were defined as mimic+OE-KIF23 group: The KIF23-3'UTR wild-type vector (KIF23-WT) and the mutant vector (KIF23-MT) were co-transfected with miR-424-5p micic and mimic NC, respectively, and the targeting relationship between miR-424-5p and KIF23 was verified by dual-luciferase reporting experiments. The cell counting Kit-8 (CCK-8) was used to detect HepG2 cell proliferation and sensitivity to sorafenib. Flow cytometry was used to assess apoptosis in HepG2 cells. Transwell and scratch experiments were used to detect HepG2 cell migration and invasion capabilities. Intergroup data were compared using t-tests or analysis of variance. Results: Compared with the paracancerous tissue and normal hepatocytes, miR-424-5p in the HCC tissue and hepatocellular cells was significantly down-regulated (the relative expression was 0.604±0.121, 0.585±0.064), and KIF23 was significantly up-regulated (the relative expression was 5.451±1.834, 2.482±0.545), P<0.05. miR-424-5p mimic can inhibit the proliferation, migration and invasion of HCC cells and promote apoptosis of HCC cells (P<0.05). Overexpression of KIF23 can promote the proliferation, migration and invasion of HCC cells and inhibit apoptosis of HCC cells (P<0.05). The luciferase activity of HepG2 cells in the mimic and KIF23-WT co-transfection groups was significantly reduced compared with HepG2 cells in the mimic NC and KIF23-WT co-transfection groups (the relative fluorescence intensities were 3.668±0.091 and 2.629±0.056, respectively, P<0.05),however, there was no significant comparison between the luciferase activity of cells in the mimic and KIF23-MT co-transfection groups compared with those in the mimic NC and KIF23-MT co-transfection groups. miR-424-5p mimic can reverse the role of overexpression of KIF23 in promoting the ability of HCC cells to proliferate, migrate and invade (P<0.05). The inhibition rates of sorafenib on HepG2 cells in the mimic+OE-KIF23 group and the OE-KIF23 group were 47.491%±3.863% and 36.246%±6.063% (t=3.027, P<0.05). Conclusion: miR-424-5p can inhibit the proliferation, migration and invasion of HCC cells and can increase the sensitivity of HCC cells to sorafenib by targeting the expression level of KIF23.

[Analysis of the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 for intrahepatic parenchymal substantial lesions ≤3.0 cm].

Objective: To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm. Methods: A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results: The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively. Conclusions: LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

[Septic shock induced by latent odontogenic orbital infection: a case report].

A 65-year-old patient was admitted to the hospital due to proptosis of the left eye accompanied with ophthalmodynia and toothache for two months. Ophthalmic examination revealed a palpable mass around the lateral orbit and temporal fossa, and maxillofacial CT suggested a malignant tumor invading the left orbital floor wall. One week later, the patient was diagnosed with left orbital cellulitis and septic shock due to peri-orbit redness, eyelid edema, chest tightness, nausea, vomiting, hypotension, and a marked increase in peripheral blood neutrophil count. The infection was well controlled after remission of shock, anti-infective therapy and surgical drainage. At 2 months after surgery, the surgical incision of the upper eyelid skin recovered well and the best corrected visual acuity of the left eye was 1.0.

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Use of the supraclavicular artery island flap for reconstruction of maxillofacial defects: a case report and literature review.

BACKGROUND: Free flaps are widely used in maxillofacial reconstruction; however, this approach was not feasible in the current case. It was not possible because the free flap method requires microvascular anastomosis expertise, which is difficult, time-consuming and costly. CASE PRESENTATION: An 86-year-old woman suffered squamous cell carcinoma on the right side of her face, which resulted in a large soft-tissue defect. Here, we present a case of facial reconstruction from the inferior margin of the jaw to the top of the head. The size of the defect was 18.5 cm × 7.5 cm, which is rare for a patient of this age in the maxillofacial area. We used the supraclavicular artery island flap (SCAIFP) which measured 19.3 cm × 8.3 cm to repair the defect. After the operation, the flap survived without complications. Then, the patient was followed for 10 months and was satisfied with the aesthetic and functional results at the donor and recipient sites following the tumour resection. The tumour did not recur, and facial nerve function was preserved. CONCLUSION: Our results provide a new choice for the reconstruction of large defects of the head and face, and expand the potential applications of the SCAIFP.

[Effect of laparoscopic novel W-H fundoplication in patients with proton pump inhibitor dependent gastroesophageal reflux disease].

Objective: To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). Methods: The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire. Results: A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P<0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation. Conclusions: The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension.

As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.

A pilot randomised controlled trial of the management of systolic blood pressure during endovascular thrombectomy for acute ischaemic stroke.

It is unknown whether systolic blood pressure augmentation during endovascular thrombectomy improves clinical outcomes. This pilot randomised controlled trial aimed to assess the feasibility of differential systolic blood pressure targeting during endovascular thrombectomy procedures for anterior circulation ischaemic stroke. Fifty-one eligible patients fulfilling the national criteria for endovascular thrombectomy were randomly assigned to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel. Systolic blood pressure targets for the standard and augmented groups were 130-150 mmHg and 160-180 mmHg, respectively. The study achieved all feasibility targets, including a recruitment rate of 3.5 participants per week and median (IQR [range]) of mean systolic blood pressure separation between groups of 139 (135-143 [115-154]) vs. 167 (150-175 [113-188]) mmHg, p < 0.001. Data completeness was 99%. Independent functional recovery at 90 days (modified Rankin Scale 0, 1 or 2) was achieved in 30 (59%) patients, which is consistent with previously published data. There were no safety concerns with trial procedures. In conclusion, a large randomised controlled efficacy trial of standard vs. augmented systolic blood pressure management during endovascular thrombectomy is feasible.

CRISPR-dCas9-mediated knockdown of prtR, an essential gene in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a widely distributed non-fermentative Gram-negative opportunistic pathogen that is often responsible for nosocomial infections. Gene interference is a potentially valuable tool for investigating essential genes in P. aeruginosa. To establish a gene interference platform in P. aeruginosa, CRISPR system was used with an inactive Cas9 protein. The CRISPR-dCas9 system was cloned into pHERD20T, a shuttle vector with arabinose inducible promoter, and was further modified to target a regulatory gene prtR that is essential for the viability of P. aeruginosa. Cells expressing the prtR-targeting CRISPR interference (CRISPRi) showed growth defect in an arabinose dose-dependent manner. A high-throughput RNA sequencing analysis of bacterial cells with or without the CRISPRi-mediated prtR inhibition indicated that prtRis a global regulator affecting multiple biological processes. In conclusion, the CRISPR-dCas9-based gene knockdown system has been successfully implemented in P. aeruginosa and demonstrated to be an effective tool in the investigation of essential or difficult-to-inactivate genes in this species.

[Change and relationship between Gli1 and ß-catenin on rats' bone formation with chronic fluorosis].

Objective: To investigate the change and association of glioma-associated oncogene homolog 1 (Gli1) and ß-catenin on bone formation in rats with chronic fluorosis which were inhibited by cyclopamine (Cycl). Methods: Forty-eight Sprague-Dawley rats were evenly divided to four groups, including control, F, F+Cycl and F+DMSO groups. The control group were fed with tap water (NaF<1 ppm). The F, F+Cycl and F+DMSO groups were exposed to NaF (50 ppm) in drinking water as the chronic fluorosis model. Then the rats in F+Cycl or F+DMSO groups were injected by Cycl or DMSO after 6 months, respectively. Urine fluoride concentration was detected using fluorine ion selective electrode. The enzyme-linked immunosorbent assay (ELISA) was used to detect bone alkaline phosphatase (BALP). Bone tissues were stained with hematoxylin-eosin. The mRNA and protein expression of Gli1 and ß-catenin in bone tissue were detected using real-time PCR, immunohistochemistry and Western blot. Results: Compared with the controls, the urine fluoride concentration and the width and volume of bone trabeculae were increased in the F, F+Cycl and F+DMSO groups, but no statistical difference among the 3 fluorosis groups. The concentration of BALP was increased in the F group and decreased in F+Cycl group (P<0.05). The expression of Gli1 and ß-catenin mRNA and protein was higher in the F and F+Cycl groups than controls, but lower in the F+Cycl group than in the F group. There was positive correlation between the expression of Gli1 and ß-catenin (r=0.476, P<0.05). The expression of Gli1 and ß-catenin was also associated with BALP concentration and volume of bone trabeculae, respectively (r(1)=0.457, r(2)=0.466, r(3)=0.581, r(4)=0.554, respectively, P<0.05 for all). Conclusions: The expression of Gli1 can be inhibited by Cycl. It may be involved in the bone formation of rats with chronic fluorosis. It may also affect the expression of ß-catenin, which is an osteogenesis factor.

[The effects and mechanism of baicalin in a mouse acute hypertensive glaucoma model].

Objective: To explore the potential neuroprotection effects and associated mechanism of baicalin in a rodent acute hypertensive glaucoma model and oxygen-glucose deprivation/reperfusion (OGD/R) induced retinal ganglion cell (RGC) injury. Methods: Experiment research. A rapid and substantial elevation of intraocular pressure was performed to establish an acute hypertensive glaucoma model, and retinal thickness was assessed at 1, 3, 5, and 7 days. The mice were then randomly divided into three groups: normal control group, hypertension group, and baicalin (50 mg/kg) for hypertension group. The effects of baicalin on the RGCs were evaluated by retrograde transporting of Fluoro-Gold. The mRNA levels of tumor necrosis factor-α, interleukine-1ß (IL-1ß), and inducible nitric oxide synthase were detected by real-time PCR, and the protein levels were measured by Western blot in the retina tissue of acute hypertensive glaucoma model. Purified primary RGC survival under OGD/R stress was measured by flow cytometry, which was also performed to measure the survival rate of RGCs pretreated by different doses of baicalin (2.5 µmol/L, 5.0 µmol/L, and 10.0 µmol/L). The effects of baicalin on primary RGCs co-cultured with mouse microglia cell line BV2 were evaluated by flow cytometry. The cytokine IL-1ß in the culture supernatant was measured by immunochemical analyses. Statistical analysis was performed using analysis of variance. Results: Retinal tissue injuries and RGC loss were observed both in vivo and in vitro. Retinal thickness was decreased to 87.32%±0.94% at 3 days (t=6.73, P<0.01), 74.86%±2.43% at 5 days (t=13.40, P<0.01), and 63.53%±2.15% at 7 days (t=19.46, P<0.01). Treatment of 50 mg/kg baicalin significantly promoted the RGC survival from 61.32%±5.94% to 89.93%±10.08% (t=4.84, P<0.01). Baicalin alleviated the retinal damages by suppressing the expression of inflammatory cytokines as revealed by Western blot and real-time PCR. In vitro the RGC survival under OGD/R stress was increased from 51.53%±1.36% to 69.37%±7.09% and 66.23%±4.25% with 5.0, 10.0 µmol/L baicalin administration (t=5.50, 4.53; both P<0.01). BV2 under OGD/R stress did extra damage to RGCs, and baicalin could reverse the damages and increase the survival from 69.37%±7.09% to 73.00%±5.20% (t=2.82, P=0.048) by reducing the release of IL-1ß [(39.97±8.76) pg/ml vs. (61.33±5.78) pg/ml, t=4.19, P=0.010]. Conclusion: Baicalin could alleviate retina tissue injury directly and promote the survival of RGCs by downregulating the expression of inflammatory cytokines and protecting RGCs from ischemia reperfusion injury. (Chin J Ophthalmol, 2020, 56: 376-382).

[Involvement of Src kinase in the down-regulation of ultra-rapid delayed rectifier K(+)current induced by tumor necrosis factor-α in cardiomyocytes].

Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 µmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.

Genetic and cytological analyses reveal the recombination landscape of a partially differentiated plant sex chromosome in kiwifruit.

BACKGROUND: Angiosperm sex chromosomes, where present, are generally recently evolved. The key step in initiating the development of sex chromosomes from autosomes is the establishment of a sex-determining locus within a region of non-recombination. To better understand early sex chromosome evolution, it is important to determine the process by which recombination is suppressed around the sex determining genes. We have used the dioecious angiosperm kiwifruit Actinidia chinensis var. chinensis, which has an active-Y sex chromosome system, to study recombination rates around the sex locus, to better understand key events in the development of sex chromosomes. RESULTS: We have confirmed the sex-determining region (SDR) in A. chinensis var. chinensis, using a combination of high density genetic mapping and fluorescent in situ hybridisation (FISH) of Bacterial Artificial Chromosomes (BACs) linked to the sex markers onto pachytene chromosomes. The SDR is a subtelomeric non-recombining region adjacent to the nucleolar organiser region (NOR). A region of restricted recombination of around 6 Mbp in size in both male and female maps spans the SDR and covers around a third of chromosome 25. CONCLUSIONS: As recombination is suppressed over a similar region between X chromosomes and between and X and Y chromosomes, we propose that recombination is suppressed in this region because of the proximity of the NOR and the centromere, with both the NOR and centromere suppressing recombination, and this predates suppressed recombination due to differences between X and Y chromosomes. Such regions of suppressed recombination in the genome provide an opportunity for the evolution of sex chromosomes, if a sex-determining locus develops there or translocates into this region.