Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

Hyperpolarization-activated cyclic nucleotide-gated(HCN)channels are widely expressed in the central and peripheral nervous systems.They can generate hyperpolarization-activated current(Ih)that regulates the resting membrane potential and excitability of neurons.Furthermore,it can affect the precise processing and con-duction of hearing,which plays a crucial role in the accurate analysis of temporal information.Therefore,through the review of HCN channel structure and distribution,as well as electrophysiological effects,the role and mecha-nism of HCN channels in the auditory pathways of the normal and unilateral or bilateral deafness patients will be fur-ther investigated.

Objective To establish a safe disposal management program for home used sharps waste of insulin injection so as to provide a reference for the standardised management of sharps waste after insulin.injection.Methods Based on the model of information-motivation-behavioural skills,the safe disposal management program for insulin needles used at home was developed by literature reviews and semi-structured interviews to investigate the perceptions and requirements of patients.The program was then modified and refined by two rounds of expert consultation with Delphi method.Results The effective retrieval rates of questionnaire for two rounds of expert consultations were 88.89%and 93.75%,with an expert authority coefficient at 0.93.In the second round,the mean importance scores of the items were 4.40 to 5.00,with a coefficient of variation ranged from 0 to 0.168.The established program consisted of three primary items,six secondary items,and 20 tertiary items.Conclusion The safe disposal management program for home used sharps waste of insulin injection established from the perspectives of information,motivation and behavioural skills was scientific and practical,which offered a guidance to healthcare professionals in the clinical practices.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective:To retrieve and summarize the best evidence related to the management of insulin injection-related sharps waste disposal in diabetic patients at home and abroad, so as to provide reference for clinical healthcare professionals.Methods:This was a evidence-based research. Evidence on insulin injection-related sharps waste management in patients with diabetes, including guidelines, expert consensus, evidence summaries, best practice information sheet, recommended practices, clinical decisions and systematic reviews was systematically searched from domestic and international databases and professional websites, and the search time frame was from the establishment of the database to December 2021. Evidence was extracted and summarized following a quality evaluation of the literature that met the criteria.Results:A total of 15 papers were included, summarizing 25 pieces of best evidence on four areas including risk assessment and management of sharps waste associated with insulin injections, education and training, and the use of safe devices and sharps containers.Conclusions:Best evidence on the management of insulin injection-related sharps waste disposal provides evidence to support clinical practice for healthcare professionals to standardized sharps waste disposal practices in patients with diabetes.

Objective:To develop Insulin Pen Waste Needles Disposal Behavior Scale for Diabetic Patients and test its reliability and validity.Methods:Using the model of information, motivation and behavior skills as the theoretical framework, the item pool was constructed by literature review, semi-structured interview and expert consultation, and the test scale was formed after a small sample pre-survey. In July 2022, 158 and 204 diabetes patients who self-injected insulin in Endocrinology Outpatient Department of a general hospital in Shanghai were selected by the convenient sampling method. Two questionnaires were conducted to test the reliability and validity of the scale.Results:Insulin Pen Waste Needles Disposal Behavior Scale for Diabetic Patients included four dimensions, such as disposal behavior cognition, disposal behavior motivation, disposal behavior skills, and safe disposal behavior, with a total of 16 items. Four common factors were extracted from exploratory factor analysis, and the cumulative variance contribution rate was 73.80%. Content validity index was 0.98 at the average scale level, 0.88 at the level of unanimity scale, and 0.83-1.00 at the level of each item. The results of confirmatory factor analysis showed that the scale structure was stable. The Cronbach's α coefficient of the scale was 0.908, the Cronbach's α coefficient of the four factors was 0.858-0.901, the split half reliability coefficient was 0.941, and the retest reliability coefficient was 0.819.Conclusions:The scale constructed in this study has good reliability and validity, which can provide a scientific and effective assessment tool for medical staff to evaluate the disposal behavior of discarded needles used for insulin pens in diabetic patients.

Objective:To explore the causal relationship between body mass index (BMI) and hypothyroidism using the two-sample Mendelian randomization model.Methods:A large-scale anthropometric genome-wide association study published in the GIANT database was used to select single nucleotide polymorphisms (SNPs) which were statistically significantly associated with BMI as an instrumental variable ( P<5×10 -8, linkage disequilibrium r 2<0.1). The causal relationship between BMI and hypothyroidism was determined by the inverse variance weighted (IVW), weighted median method and the MR-Egger method, respectively. A heterogeneity test, gene pleiotropy test, and sensitivity analysis were performed to evaluate the stability and reliability of the results. Results:A total of 89 SNPs related to BMI were screened out as instrumental variables. IVW analysis suggested that for every standard deviation increase in BMI, the risk of hypothyroidism increased by 0.9% (odd ratio ( OR)=1.009, 95% confidence interval ( CI): 1.006-1.012, P<0.001). Similar results were obtained with the weighted median method ( OR=1.007, 95% CI: 1.002-1.011, P=0.003) and the MR-Egger method ( OR=1.008, 95% CI: 1.001-1.015, P=0.006). The MR-Egger analysis showed that genetic pleiotropy did not bias the results (intercept=0.000 1, P=0.776), the one-by-one exclusion method did not show that a single instrumental variable SNP had a significant impact on the results, and the difference was not statistically significant ( P>0.05). Conclusion:Mendelian randomized analysis showed a positive causal relationship between BMI and hypothyroidism.

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d_0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m²·g^-1 and 12.512 m²·g^-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m^-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m^-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.