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Hereditary aceruloplasminemia (ACP) is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin (CP) gene mutation and defective or absent CP function. In the present study, we report a case of ACP in a 34-year-old Chinese woman with diabetes, fatigue, anxiety, and progressive membrane loss with low hemoglobin associated with microcytosis. The fasting glucose level was 5.6-7.96 mmol/L. Postprandial blood glucose ranged from 6.8 to 9.6 mmol/L. The Stumvoll first-phase and second-phase insulin secretion disposition indices were very low, and the serum iron content was low, even though transferrin levels were normal. Moreover, the transferrin saturation was low (5%), and the ferritin level was extremely high, above 2,000 μg/L in the patient. Furthermore, her serum CP level was extremely low ( A) in the CP gene and was diagnosed with ACP. To date, less than 60 family cases of ACP have been reported worldwide, and only two cases of ACP have been reported in China. Here, we report a case of ACP accompanied by diabetes with a novel mutation of the CP gene, which suggests that increased awareness should be highlighted in this disorder as diabetes is an important typical symptom.

In marine continental margins, high saturations of natural gas hydrate are observed within the gas hydrate stability zone, but the gas migration pathways to the hydrate reservoir are not often clear. We focus on a site in Green Canyon Block 955 (GC 955) in the Gulf of Mexico, where gas hydrate occurs in a 35 m-thick reservoir with saturations of 79-93% in numerous centimeter- to decimeter-thick sandy silt layers and little to no gas hydrate in the interbedded cm to decimeter-thick clayey silt layers. Different datasets (well logging, coring, and seismic data) suggest different types of potential methane migration mechanisms. For example, relatively high particulate organic carbon content in the reservoir and the microbial methane source indicated by gas chromatography and methane isotopes suggest gas might be made locally and migration could occur through dissolved methane sources or water advection. In contrast, the visible deeply rooted faults intersecting the gas hydrate reservoir and the gas pockets adjacent to the faults on seismic data suggest that free gas may migrate directly into the reservoir. We tested three different mechanisms to form gas hydrate at GC 955: short-range methane diffusion, short-range methane diffusion coupled with upward water advection, and free gas flow. The 1-D and 2-D numerical models show that both the short-range migration and the upward water advection are not enough to form high saturations gas hydrate at GC 955, and that free gas flow is required to form the high saturations of gas hydrate observed at GC 955.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with a median survival time of 3‒5 years. Inaccurate diagnosis, limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need. In recent years, it was reported that DDRs are potential targets in anti-fibrosis treatment. Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases, such as RET, AXL and ALK. Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities, low toxicity, good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy. Therefore, we confirmed that discoidin domain receptors are promising drug targets for IPF, and compound 47 would be a promising candidate for further drug development.

Renewable energy generation, as part of the global effort to mitigate climate change, will play a central role in reducing greenhouse gas emissions and achieving China’s goal of carbon emissions peak before 2030 and carbon neutral before 2060. However, the impact of carbon quota auctions on renewable energy generation has not been sufficiently discussed. The main purpose of this study is to investigate whether China can rely on quota auctions to increase renewable energy generation in the short term, and to demonstrate which is more effective in promoting renewable energy development, policy enforcement or auction constraints? The improved neo-trans-log production model, the multi-objective linear programming model and the dispatch heuristic were used to predict additional emission reduction cost, optimized power mix with different auctioning rates, with economic development, technological progress and the unique characteristics of China's power generation industry being taken into consideration. The results show that the auctioning rate will have little influence on the optimized energy production structure, especially on the share of renewable energy resources; when the total on-grid electricity generation ranges from 7625‒7926 billion kW h and the auctioning rate ranges from 0%‒5%, policy enforcement will influence the generation of renewable energy to a greater extent than auctioning in the near future.

Background Brugada syndrome is a major cause of sudden cardiac death in young people with a distinctive electrocardiogram (ECG) feature. We aimed to develop a deep learning-enabled ECG model for automatic screening Brugada syndrome to identify these patients at an early time, thus allowing for life-saving therapy. Methods A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was further validated in the independent ECG dataset, collected from the hospitals in Taiwan and Japan. Results The diagnoses by the deep learning model (AUC: 0.96, sensitivity: 88.4%, specificity: 89.1%) were highly consistent with the standard diagnoses (Kappa coefficient: 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity: 86.0%, specificity: 90.0%). Conclusions We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivaling trained physicians.

Objective Transcutaneous auricular vagus nerve stimulation (taVNS) can relieve the symptoms of functional dyspepsia (FD) and improve the quality of life of patients, however, the mechanism underlying this effect remains unclear. Therefore, this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins. Methods This study was conducted on 24 specific Spathogen-free Sprague–Dawley rats (12 males and 12 females). The rat model of FD was established by tail-clip stimulation. After FD was established successfully, all rats were randomized to either the normal group (n = 6), model group (n = 6), taVNS group (n = 6), or sham-taVNS group (n = 6). After two weeks of the respective intervention, the score of their general conditions, 3 h food intake, gastric emptying rate, and the histology of gastric antrum tissues were observed to evaluate modeling success, and then the effect of taVNS was evaluated. Western blotting was used to assess the expression of the tight junction ligandins —ZO-1 and occludin—and the adhesion ligandin—β-catenin—in the duodenum. The effect of taVNs on the expression of intestinal mucosal barrier ligandins—ZO-1, occludin, and β-catenin—in FD rats was preliminarily investigated. Results When the model-induced period was finished, the manifestations of FD in the model group rats were mental exhaustion, reduced activities, decreased score of the general conditions, and decreased 3 h food intake, compared to the normal group rats. In addition, minimal eosinophil infiltration, without any mucosal erosion or ulcer, was observed in the gastric antrum mucosa. At the end of the study, the mental state of the FD rats improved, and their activities and gastric emptying rate increased in the taVNS group rats. Compared to the normal rats, the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin, but β-catenin expression remained unchangedin the model rats. The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention. Conclusion TaVNS can improve the gastric motility and mental state of rats with FD. It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa, while also repairing the duodenal mucosal barrier.

Objective The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyze the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort. Study design Retrospective cohort study. Setting A health management center in Taiwan. Participants Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later. Main outcome measures Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis. Results The present study consisted of 6,974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was 0.74 for participants with 5-7 ideal CVH metrics (95% CI, 0.59-0.93, p=0.01) compared to those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was 0.72 (95% CI, 0.58-0.89, p=0.003). Conclusions Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.

In spite of the preliminary evidence suggesting a link between gestational use of antidepressant and neurodevelopmental disorders in their offspring, the association between maternal use of antidepressants during pregnancy and the risk of neurologically-related adverse outcomes such as neonatal seizure is still unclear. This study summarises the available evidence on the association between gestational exposure to any antidepressants and the risk of seizure in neonates and children. We found that gestational antidepressant exposure is associated with a 2.3-fold higher incidence of seizure in offspring. Although a causal relationship cannot be confirmed in view of other potential confounders, our findings warrant future research on related clinical aspects, and possibly more careful monitoring of foetal neurodevelopment in pregnant women taking antidepressants during pregnancy. However, this does not suggest the abrupt withdrawal of antidepressants during pregnancy for all cases at risk of seizure in offspring as this must be balanced with the risk of negative consequences caused by untreated maternal depression, and decision-making should be individualised for each patient.

Background Gastroesophageal reflux disease (GERD) is associated with lower esophageal sphincter (LES) incompetence. In some patients, GERD is refractory to acid reduction therapy which is the main treatment for GERD. So far, medications that can increase LES tone are few. Arecae pericarpium (A. pericarpium) is a medication in Traditional Chinese Medicine known to promote intestinal motility. Methods We investigated the effect of A. pericarpium extracts on porcine LES motility. In addition, we used tetrodotoxin (TTX) and atropine to study the underlying mechanism of A. pericarpium extracts-induced contractions of LES. Results The results of this study showed that A. pericarpium extracts and their main active ingredient, arecoline, can induce the contractions of porcine LES sling and clasp muscles in a dose-response manner. TTX did not have an inhibitory effect on the contractions induced by A. pericarpium extracts and arecoline in LES. However, atropine significantly inhibited A. pericarpium extracts- and arecoline-induced contractions of LES. Conclusion A. pericarpium extracts can induce the contractions of porcine LES in a dose dependent manner, possibly through muscarinic receptors, and hence, may be worth developing as an alternative therapy for GERD.

Regenerative endodontics (RE) therapy means physiologically replacing damaged pulp tissue and regaining functional dentin-pulp complex. Current clinical RE procedures recruit endogenous stem cells from the apical papilla, periodontal tissue, bone marrow and peripheral blood, with or without application of scaffolds and growth factors in the root canal space, resulting in cementum-like and bone-like tissue formation. Without the involvement of dental pulp stem cells (DPSCs), it is unlikely that functional pulp regeneration can be achieved, even though acceptable repair can be acquired. DPSCs, due to their specific odontogenic potential, high proliferation, neurovascular property, and easy accessibility, are considered as the most eligible cell source for dentin-pulp regeneration. The regenerative potential of DPSCs has been demonstrated by recent clinical progress. DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp. The self-renewal, proliferation, and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors. Over recent decades, epigenetic modulations implicating histone modifications, DNA methylation, and noncoding (nc)RNAs have manifested as a new layer of gene regulation. These modulations exhibit a profound effect on the cellular activities of DPSCs. In this review, we offer an overview about epigenetic regulation of the fate of DPSCs; in particular, on the proliferation, odontogenic differentiation, angiogenesis, and neurogenesis. We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.

Acid mine drainage commonly occupies some pore space after underground coal mining, and this severely depreciates coal pillars, thereby posing a significant risk to mine stability. Considering that such depreciation is reflected in the microstructures of these pillars, in the present study, we propose a static immersion method suitable for coal seam samples immersion in the laboratory. We immersed the No. 2–2 coal seam samples from the Ningtiao Tower Coal Mine in Yulin, Shaanxi Province, in different acid mine drainage solutions and monitored the pH, oxidation–reduction potential (ORP), electrical conductivity (EC), total dissolved solids (TDS) among other water quality parameters for 300 h. After the immersion tests, samples were examined using scanning electron microscopy (SEM). The pH, ORP, EC, and TDS of the prepared acid mine drainage solutions increased significantly as the immersion time increased. Changes in water quality parameters are attributed to the absorption of hydrogen ions by insoluble clay minerals in the coal, which reduced the acidity, increased the pH value, and enhanced the electrical conductivity of the acid mine drainage solutions. SEM analysis reveals differences in the pore characteristics of (pore throat size and orientation) of the coal samples, and these are caused by erosive effects of the acid mine drainage solutions. Pores with throat sizes greater than 10 μ m increased by 95% as the pH of the acid mine drainage solutions decreased, while the dominant pore orientation (60–90°) decreased to the 0–30° or increased to the 150–180° range, thereby increasing their randomness.

Background Although open reduction and internal fixation (ORIF) is recommended for lateral condylar humerus fractures (LCHFs) displaced by > 4 mm, several studies have reported the use of closed reduction and percutaneous pinning (CRPP) to treat LCHFs with significant displacement. However, little is known about the clinical differences between these two surgical techniques. This study aimed to compare the therapeutic effects of CRPP and ORIF in treating LCHFs displaced by > 4 mm. Methods We retrospectively reviewed pediatric LCHFs displaced by > 4 mm treated with either CRPP or ORIF at our center from June 2019 to October 2020. Song and Milch fracture classifications were used. Variables such as age at injury, sex, side injured, fracture displacement, fracture type, operating time, postoperative treatment, and complications were compared between the two techniques. Results One hundred twenty LCHFs met inclusion criteria. There were 36 Milch type I and 84 type II LCHFs, and 69 Song stage 4 and 51 stage 5 LCHFs. CRPP was performed in 45 cases and ORIF in 75 cases. No differences were found in age, sex, side injured, preoperative displacement, postoperative displacement, and length of immobilization between the CRPP and ORIF groups. There was a difference between operation time and pin duration. The CRPP group had shorter operation times and pin duration, and required no additional operations to remove internal pins. The average follow-up duration was 13.9 months. All patients achieved fracture union, and no complications such as infection, nonunion, delayed union, osteonecrosis, fishtail deformity, cubitus varus or valgus, or pain were recorded during follow-up. Bone spurs, lateral prominences, and decreased carrying angle were common complications in all groups. No obvious cubitus varus was observed. Unaesthetic scars were only observed in the ORIF groups. No differences in range of motion or elbow function was found among the different therapies. Conclusions Both CRPP and ORIF can achieve satisfactory clinical outcomes in treating LCHFs displaced by > 4 mm. No differences were found in complications or prognoses between the two groups. However, CRPP shows some advantages over ORIF, like less invasive surgery, no obvious scarring, and no need for secondary surgery with anesthesia for pin removal.

BACKGROUND Postconcussion symptoms (PCSs) are common complaints reported by patients after a mild traumatic brain injury (TBI), and these symptoms may lower quality of life. Previous investigations have primarily focused on PCSs in children, adults, and athletes. The frequency, and risk factors, and effects of PCSs for older adults with mild TBIs are unclear. PURPOSE To investigate the frequency and risk factors of PCSs, and investigate their effects on quality of life over time after mild TBI in older adults. METHODS A prospective longitudinal study was performed. All participants were enrolled from the emergency department or neurosurgical outpatient clinics of a medical center. The measurement tools were the Rivermead Post-Concussion Symptoms Questionnaire and the Quality of Life after Traumatic Brain Injury. Measurements were performed on the seventh day, at the first month, and at the sixth month after the head injury. A generalized estimating equation model was used for data analyses. RESULTS One hundred and one older adults (mean age of 76.0 years) with mild TBIs with negative neuroimaging findings were included. Overall, 32.7%, 4%, and 15.8% of the sample reported PCS after 7 days, 1 month, and 6 months of head injury, respectively, revealing a U-shaped trend. We observed that comorbidity measured using the modified Charlson Comorbidity Index was associated with differences in PCSs (P < .05). PCSs were an independent predictor of changes in postinjury quality of life (P < .001). CONCLUSIONS The results indicate that PCS after a mild TBI in older adults is prevalent, even in the chronic phase after a TBI, and PCSs significantly affected the quality of life of our cohort. Therefore, to improve patient quality of life, healthcare providers should employ effective interventions to manage PCSs at different phases after a TBI.

E-commerce supply chain actually deals with the acquisition of the raw materials, their timely processing, and on-time delivery to the right place. It deals with a number of processes such as supply and demand, managing order entry, and inventory tracking. Now profit distribution models are actually stochastic models that are used to optimize the gains and profits in a particular business. They actually generate modern time solutions to the existing problems in a sustainable environment. However, in order to solve the problems existing in the traditional profit distribution algorithm of the e-commerce supply chain, such as low distribution accuracy and large time cost, a profit distribution algorithm of the e-commerce supply chain under the concept of sustainable development was designed. It was supported by the concept of sustainable development, and the coefficient of income distribution is calculated according to the equilibrium bidding strategy of supply chain alliance and its members, net present value of income distribution, total investment, minimum expected rate of return on investment, and other parameters. First, calculate the Shapley value of the profit distribution of the power supply chain, and obtain the correction coefficient through the correction matrix, dimensionless processing, and analytic hierarchy process. Use the correction coefficient to correct the Shapley value and the income distribution coefficient to realize the design of the profit distribution algorithm for the power supply chain. The experimental results show that the algorithm has low relative error rate, high precision, and short time cost of profit distribution coefficient calculation.

Background Due to its limited efficacy and potential toxicity, anti-PD-1 monoclonal antibody is not suitable for all advanced gastric cancer (AGC) patients and predictive biomarkers identifying patients who can benefit from it are urgently needed. This study aimed to evaluate the predictive and prognostic value of inflammatory markers in the context of the systemic inflammatory status and tumour microenvironment. Methods The study included 58 patients from a prospective study investigating the safety and efficacy of toripalimab in chemorefractory AGC patients. Patient characteristics, treatment outcomes, and haematological parameters were analysed. Immune-cell infiltration and gene expression in tumour tissue were examined using transcriptome sequencing. Results In this cohort, the median follow-up time was 4.5 months, the median progression-free survival was 1.9 months, and the median overall survival (OS) was 4.8 months. The objective response rate was 12.1% and th disease control rate (DCR) was 39.7%. Both the baseline blood neutrophil-to-lymphocyte ratio (bNLR) with a cut-point of 2.7 and the early elevated dynamic change of the bNLR (dNLR) with a cut-point of 1.5 were prognostic factors of survival. Patients in the high bNLR or dNLR group had remarkably poor DCR (25.8% vs 59.1%, P = 0.023; 15.8% vs 54.6%, P = 0.008). In multivariate analysis, bNLR and tumour mutational burden were independent prognostic factors of OS. Tumour RNA-seq analysis revealed enriched neutrophil infiltration and a higher tumour NLR in the bNLR-high group. Corresponding tumour gene-expression profiles were associated with neutrophil recruitment and inflammatory cytokine aggregation. Conclusions Our study demonstrated the potential clinical utility of NLR as a biomarker for patient selection and clinical management in predicting the prognosis of AGC patients as well as response to anti-PD-1 therapy. In addition, high bNLR reflected the imbalance of tumour-tissue-infiltrating neutrophils and lymphocytes, and was associated with an immunosuppressive and pro-tumour microenvironment.

Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

To observe the effects of acupoints, cone numbers and durations of moxibustion with different moxibustion methods on skin surface and inside temperature, and to provide references for the clinical standardization of moxibustion amount. The 42 big-ear white rabbits were divided into 6 groups according to the random number table method, a 1-cone direct moxibustion group, a 2-cone direct moxibustion group, a 3-cone direct moxibustion group, a 1-cone herbal cake-partitioned moxibustion group, a 2-cone herbal cake-partitioned moxibustion group, and a 3-cone herbal cake-partitioned moxibustion group, with 7 rabbits in each group. Shenque (CV 8), Shenshu (BL 23) and Zusanli (ST 36) were used in each group, but the moxibustion methods, cone numbers and durations of moxibustion were different. Rabbits in each group received moxibustion once every other day for 5 times in total. During the intervention, a thermoelectricity coupled probe and a temperature recorder were used to record the real-time acupoint skin temperature and the temperature at different time points, so as to observe, analyze and process the real-time changes in the temperature difference between the surface and inside of acupoint skin. For herbal cake-partitioned moxibustion, the best temperature for cone changing was (46.38±0.51) °C when the highest surface temperature was (49.20±0.52) °C; the multi-factor comparison of acupoint × cone number × time and acupoint × moxibustion method × time showed that time × acupoint, time × moxibustion method and cone number × acupoint had interactive effects (all P

Importance : The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.\ud \ud Objective : To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems.\ud \ud Design, Setting, and Participants : This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.\ud \ud Exposures : Prenatal antipsychotic exposure.\ud \ud Main Outcomes and Measures : Preterm birth (

Background Fluid overload is associated with poor outcomes. Clinicians might be reluctant to initiate diuretic therapy for patients with recent vasopressor use. We estimated the effect on 30-day mortality of withholding or delaying diuretics after vasopressor use in patients with probable fluid overload. Methods This was a retrospective cohort study of adults admitted to ICUs of an academic medical centre between 2008 and 2012. Using a database of time-stamped patient records, we followed individuals from the time they first required vasopressor support and had >5 L cumulative positive fluid balance (plus additional inclusion/exclusion criteria). We compared mortality under usual care (the mix of care actually delivered in the cohort) and treatment strategies restricting diuretic initiation during and for various durations after vasopressor use. We adjusted for baseline and time-varying confounding via inverse probability weighting. Results The study included 1501 patients, and the observed 30-day mortality rate was 11%. After adjusting for observed confounders, withholding diuretics for at least 24 h after stopping most recent vasopressor use was estimated to increase 30-day mortality rate by 2.2% (95% confidence interval [CI], 0.9–3.6%) compared with usual care. Data were consistent with moderate harm or slight benefit from withholding diuretic initiation only during concomitant vasopressor use; the estimated mortality rate increased by 0.5% (95% CI, –0.2% to 1.1%). Conclusions Withholding diuretic initiation after vasopressor use in patients with high cumulative positive balance (>5 L) was estimated to increase 30-day mortality. These findings are hypothesis generating and should be tested in a clinical trial.

Po-En Chiu,1,2,&ast; Zhonghua Fu,3,&ast; Guan-Wei Jian,4,5 Ching-Hsuan Huang,2,6 Te-Mao Li,2 Li-Wei Chou7– 9 1Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Institute of Fu’s Subcutaneous Needling, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; 5Department of Chinese Medicine, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 6Department of Chinese Traumatology Medicine, China Medical University Hospital, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 8Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 9Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Li-Wei ChouDepartment of Physical Medicine and Rehabilitation, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, 40447, TaiwanTel +886-4-22052121-2381Fax +886-4-22026041Email chouliwe@gmail.comBackground: Knee osteoarthritis (OA) is a common clinical disease. Knee pain is the major symptom of knee OA and the primary reason why patients seek treatment. Fu’s subcutaneous needling (FSN) has been used to treat knee OA for more than 20 years. However, the establishment of treatment methods and rigorous evaluation of FSN’s efficacy are still lacking. A randomized single-blind clinical trial will be conducted to evaluate whether FSN treatment can immediately alleviate pain due to knee OA surrounding the patella and the curative effective of 1-week and 2-week treatments. In addition, the feasibility and initial effect of FSN treatment for patients with knee OA will be discussed.Materials and Methods: Patients with confirmed knee OA, as diagnosed by doctors using X-ray films or from clinical symptoms, who are over 50 years old will be participants recruited. They will be randomly assigned either FSN treatment or transcutaneous electrical nerve stimulation treatment. In addition, their pressure pain threshold, muscle tone of lower leg muscle, and physical ability will be measured. Participants will be asked to complete the questionnaires of Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne’ index as the measurements for quality of life.Results: The findings of this study will reveal whether FSN or transcutaneous electrical nerve stimulation is clinically efficacious for treating pain due to knee OA, with respect to muscle stiffness, gait, dynamic balance, the pressure pain threshold, and quality of life before and after treatment.Study Registration: This study is approved by the Research Ethics Committee of China Medical University & Hospital, Taichung, Taiwan (CMUH107-REC3-027) and registered at the ClinicalTrials.gov Protocol Registration and Results System (registration number NCT04356651).Keywords: dry needling, Fu’s subcutaneous needling, knee osteoarthritis, myofascial trigger point, tightened muscle

Breast cancer is one of the most common malignancies. Pathological image processing of breast has become an important means for early diagnosis of breast cancer. Using medical image processing to assist doctors to detect potential breast cancer as early as possible has always been a hot topic in the field of medical image diagnosis. In this paper, a breast cancer recognition method based on image processing is systematically expounded from four aspects: breast cancer detection, image segmentation, image registration, and image fusion. The achievements and application scope of supervised learning, unsupervised learning, deep learning, CNN, and so on in breast cancer examination are expounded. The prospect of unsupervised learning and transfer learning for breast cancer diagnosis is prospected. Finally, the privacy protection of breast cancer patients is put forward.

After the construction of rural water supply projects, how to make them sustainably operated and managed has become the focus and difficulty of the current and future work of rural water supply. In order to evaluate the operation and management of rural water supply projects, a comprehensive indicator system of rural water supply projects sustainable operation and management was established, and a combinational evaluation model based on a cyclic correction framework was used in 13 pilot districts of Chongqing, China. The APH method was used to calculate the weight of each index. The two indexes with the highest weights are ‘establishment of management agency (0.1436)’ and ‘assurance level of operating funds (0.1382)’. Compared with the traditional individual evaluation model, the cyclic correction framework can effectively reduce the systematic deviation and random error in the evaluation process and make the research conclusion more reliable. The ranks of the districts in the main urban metropolitan part are higher, while the districts in the southeast and northeast of Chongqing are ranked relatively low. The top five districts were Rongchang, Yubei, Banan, Liangping, and Tongliang. In the future, the sustainable operation and management of rural water supply projects should be improved by enhancing the ability of the management agencies of rural water supply projects and increasing funding for project operation management.

The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24–3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

Transparent conductive oxide (TCO) semiconductors are attracted considerable attention due to a wide range of applications, such as flat panel display (FPD), touch panels, solar cells, and other optoelectronic devices. Owing to the different carrier conduction paths between n-type and P-type TCOs, the n-type TCO used in TFTs usually have high Ion/Ioff current ratio (>107) and high electron mobility (>10 cm2/V·s), P-type TCO TFTs are both lower than that of n-type one. For complementary circuits design and applications, however, both P-type and n-type semiconductor materials are equally important. For SnO thin films, it is important to adjust the ratio of Sn2+ (SnO P-type) and Sn4+ (SnO2 n-type) in order to modulate the electrical characteristics. In this investigation of post treatment for SnO thin films, both microwave annealing (MWA) and furnace annealing process with 02 ambient are studied. The results show that SnO thin films are optimized at 300 °C, 30 minutes furnace annealing, the P-type SnO/SnO2 thin film shows surface mean roughness 0.168 nm, [Sn2+]/[Sn4+] ratio as 0.838, at least 80% transmittance between 380 nm-700 nm visible light. Withthe results, SnO can be even used to fabricate high performance P-type thin film transistors (TFTs) device for future applications.

The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear.The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD.Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated.The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (10Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

Aim To compare the effects and safety of open and closed endotracheal suction in children with severe brain injury. Design A single‐blinding, single‐centre randomized controlled trial (RCT). Methods The children with severe brain injury admitted to the intensive care unit (ICU) from 1 September 2020–31 August 2022 will be included. And a total of 172 children with severe brain injury are expected to be included. The intracranial pressure, SpO2 and heart rate before suctioning, at the end of suction, and at 5 and 10 min after suction, the estimated sputum volume for each suction, the incidence of ventilator‐associated pneumonia, the duration of mechanical ventilation and the length of ICU stay will be analysed. Results This present RCT has been prospectively registered in China Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR2000030963). This present study is expected to provide reliable evidence to the airway management in children with severe brain injury.

Context In 2020, the terminology of metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Objectives This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases. Methods A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models. Results The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes. Conclusion The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non–fatty liver.

Background The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.

HDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%–35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.

Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5–12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.

Aims To study the role and characteristics of activated microglia in poststroke depression (PSD) . Methods Twenty-four male Wistar rats were randomly divided into three groups: the poststroke (PS) group, PSD group, and Sham group. Neurobehavioral testing was performed 24 h postoperation. The body weights of the rats were regularly recorded, and behavioral testing was regularly performed at 1, 2 and 3 weeks postmodeling. Immunofluorescent staining was used to detect the microglial marker OX42. Real-time PCR was used to analyze the relative gene expression of microglial activation markers (TNF-a, IL-10, IL-1, TGF-β, CD86, iNOS, CD206, IL-1β, and Arg1) . Results The relative gene expression of proinflammatory markers (IL-1, TNF-a, iNOS, and IL1β) and anti-inflammatory markers (CD206 and Arg1) significantly increased in the hippocampal region compared with that in the right cerebral and left cerebral hemispheres in the PSD group. The relative gene expression of proinflammatory markers (TNF-a, IL-1, iNOS, and CD86) in the hippocampal region was significantly increased in the PSD group compared with that in the Sham and PS groups. The anti-inflammatory markers (TGF-β and CD206) in the hippocampal region were significantly increased in the PSD group compared with that in the Sham group, and the M2 marker Arg1 was significantly increased in the PSD group compared with that in the PS group. Correlation analysis showed that IL-1 was strongly negatively correlated with PSD . Conclusions Most microglia in the hippocampal region of PSD had a proinflammatory status and an anti-inflammatory status. IL-1 showed a strong negative correlation with PSD.

BACKGROUND Anterior cruciate ligament (ACL) injury experiences about 200,000 isolated cases annually, and ACL reconstruction has become the gold standard for the restoration of stability and functionality. In view of that incorrect graft placement is a common cause of ACL reconstruction failure, it is critically important to ensure that the tibial and femoral tunnels are properly placed during the operation. Therefore, we intend to conduct a network meta-analysis to comparatively evaluate the clinical outcomes among the different surgical techniques in ACL reconstruction. METHODS Embase, PubMed, and Cochrane Library will be searched through to retrieve the relevant literature up to April 2020. The outcomes include the International Knee Documentation Committee subjective/objective score, Lachman test, Lysholm score, laxity of knee joint, pivot-shift test, Tegner activity scale, and the number of adverse events. A Bayesian hierarchical framework will be used to evaluate the comparative efficacy among different fixation devices. Cochrane Q test and I statistics will be applied to evaluate the heterogeneity, and the Cochrane risk of bias assessment tool will be employed to evaluate the study quality and the risk of bias. RESULTS The comparative risk-benefit profiles of different femoral drilling techniques will be evaluated based on the existing evidence, in order to summarize a prioritization regimen. CONCLUSION Findings from this network meta-analysis will provide useful reference to patients, surgeons, and guideline makers in the related fields. REGISTRATION Open Science Framework (OSF) Preregistration. April 20, 2020. osf.io/uzahs.

Objective Diagnostic errors are major contributors to preventable patient harm. We validated the use of an electronic health record (EHR)-based trigger (e-trigger) to measure missed opportunities in stroke diagnosis in emergency departments (EDs). Methods Using two frameworks, the Safer Dx Trigger Tools Framework and the Symptom-disease Pair Analysis of Diagnostic Error Framework, we applied a symptom–disease pair-based e-trigger to identify patients hospitalized for stroke who, in the preceding 30 days, were discharged from the ED with benign headache or dizziness diagnoses. The algorithm was applied to Veteran Affairs National Corporate Data Warehouse on patients seen between 1/1/2016 and 12/31/2017. Trained reviewers evaluated medical records for presence/absence of missed opportunities in stroke diagnosis and stroke-related red-flags, risk factors, neurological examination, and clinical interventions. Reviewers also estimated quality of clinical documentation at the index ED visit. Results We applied the e-trigger to 7,752,326 unique patients and identified 46,931 stroke-related admissions, of which 398 records were flagged as trigger-positive and reviewed. Of these, 124 had missed opportunities (positive predictive value for “missed” = 31.2%), 93 (23.4%) had no missed opportunity (non-missed), 162 (40.7%) were miscoded, and 19 (4.7%) were inconclusive. Reviewer agreement was high (87.3%, Cohen’s kappa = 0.81). Compared to the non-missed group, the missed group had more stroke risk factors (mean 3.2 vs 2.6), red flags (mean 0.5 vs 0.2), and a higher rate of inadequate documentation (66.9% vs 28.0%). Conclusion In a large national EHR repository, a symptom–disease pair-based e-trigger identified missed diagnoses of stroke with a modest positive predictive value, underscoring the need for chart review validation procedures to identify diagnostic errors in large data sets.

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually originates from oral potentially malignant disorders (OPMD), such as oral leukoplakia (OLK) and oral lichen planus (OLP). Identifying biomarkers for the early diagnosis and evaluation of malignant transformation in OPMD could improve the survival rate of OSCC patients. OBJECTIVE: The present study aimed to screen for potential salivary biomarkers for evaluating the malignant transformation of OPMD. METHODS: Salivary proteases from OLK and OSCC patients or healthy donors and proteases in cultural medium from DOK and Cal-27 cells were detected with a human protease array kit. The concentrations of the salivary Kallikrein 5 (KLK5) and urokinase-type plasminogen activator (uPA) proteases were measured by ELISA. Receiver operating characteristics (ROC) to determine the potential value of these proteases in clinical diagnosis were calculated using SPSS software. Immunohistochemistry was used to detect the KLK5 and uPA expression in the oral organizations. RESULTS: The salivary protease spectrum was different among patients with OLK and OSCC and healthy donors. KLK5 and uPA levels in saliva tended to increase as the disease progressed (healthy < OPMD [OLK and OLP] < OSCC). ROC curves showed the optimum diagnostic cutoffs for KLK5 as a biomarker for OLK, OLP, and OSCC were 5.97, 6.03, and 9.45 pg/mL, respectively, while the cutoffs for uPA were 17.19, 17.26, and 20.96 pg/mL. Their combined analysis showed a higher sensitivity for the differential diagnosis of disease. Furthermore, higher levels of KLK5 and uPA were observed in OSCC tissues than in OLK and OLP. CONCLUSIONS: Salivary KLK5 and uPA are potential biomarkers for evaluating OLK and OLP malignant transformation and early diagnosis of OSCC.

The carrier recombination was one of the factors limiting the further improvement of the Cu2ZnSnS4 (CZTS) thin film solar cells. In this paper, a proper bandgap structure was designed to solve this problem. The effects of the different bandgap structure on the CZTS thin film solar cells were studied by the solar cell performance simulation software wxAMPS. A graded bandgap structure was designed and optimized. The bandgap with a front bandgap gradient and a flat bandgap gradient had a favorable effect on the CZTS thin film solar cells. Finally, the fill factor (FF) and conversion efficiency (η) of the CZTS thin film solar cell were increased from 36.41% to 42.73% and from 6.85% to 10.03%, respectively. In addition, the effect of donor and acceptor defect densities in CZTS absorber layer near the CdS/CZTS interface on the device performance was studied, η of the CZTS thin film solar cell was increased from 5.99% to 7.55% when the acceptor defect concentration was 1012–1013 cm−3. Moreover, the thicknesses of the CZTS absorber layer were optimized. The FF and η of the CZTS thin film solar cell were increased to 63.41% and 15.04%, respectively.

Infrared small-target detection of a low signal-to-noise ratio (SNR) has been an important research hotspot. Small targets lack texture and detailed information; in addition, the background tends t...

Medical literature emphasizes, “Every medicine has its side effects”. Therefore, we have to pay more attention in advocating preventive medicine today. Above all, Huangdi neijing emphasizes the pri...

Uneven surface quality usually occurs when grinding welds offline, which results non-uniform stress and then would damage the workpiece. In this paper, the robotic welding seam online grinding system based on laser vision sensor was proposed and built. A weld seam tracking software was developed and the data online interaction method of grinding system based on XML (Extensible Markup Language) file was applied. Firstly, hand-eye calibration model was built to convert data in the robot coordinate system. Then the weld profile information was extracted and stored in the data buffer area, and the coordinates of the robotic grinding point were transmitted through the self-developed weld grinding software. Finally, the vision system and the self-made grinding system were integrated at the end of the robot. The experiments were conducted to verify the reliability and practicality of this system and the proposed data interaction online method.

Objectives To observe the clinical long-term therapeutic effect on functional dyspepsia (FD) in the comparative study of transcutaneous auricular vagus nerve stimulation (taVNS) with transcutaneous auricular none-vagus nerve stimulation (tnVNS). Methods A total of 90 FD patients were randomized into a taVNS group and a tnVNS group, 45 cases in each one. The patients in both the taNVS group and the tnVNS group were treated 5 times a week, 30 min each time, for 4 weeks totally. Before treatment, after treatment and in follow-up visit, overall symptom points, functional dyspepsia-related quality of life questionnaire (FDQOL), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD) and self-rating depression scale (SDS) were adopted to evaluate the severity of the symptoms and observe the clinical therapeutic effect of patients. Results Compared with the scores before treatment, the overall symptom points, FDDQL, HAMA, HAMD and SDS at each time point after treatment were all lower in the patients of the taVNS group. The scores of FDDQL after treatment were almost all higher than that before treatment in the self-comparison of each group. All of the above differences were significant statistically (all P Conclusion Transcutaneous auricular vagus nerve stimulation is applicable for the treatment of functional dyspepsia. Compared with the control group, taVNS obtains a better long-term effect.

A spectrum tunable method is presented for a high-birefringence fiber loop mirror (HiBi-FLM) comb filter with a polarization controller (PC) in the loop, where not only the wavelength of the comb filter can be continuously tuned with peak transmission remaining at unity, but the peak amplitude can be also continuously tuned without wavelength shift. By using the Jones matrix, we theoretically analyze the comb filter. The analytical expressions of the reflectivity and transmissivity are derived in terms of the orientation angles of three waveplates of the PC. The optimum conditions for wavelength and peak amplitude tunable operations are obtained. Our theoretical results show that when the two quarter-waveplate (QWP) angles are optimally set, the PC could act as a phase shifter or a polarization rotator, which empowers the comb filter to be wavelength continuously tunable or to be peak amplitude variable from 0 to 1 by only rotating the half-waveplate (HWP) of the PC. Moreover, the wavelength shift has a linear relationship with the HWP angle. When the two QWP angles are not optimized, PC has a combined effect of a phase shifter and a polarization rotator, leading to a wavelength shift accompanied by a change of the peak amplitude when tuning the HWP. Our theoretical prediction has been verified by experimental results.

Background and aims Lipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations. Methods This cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018 for 83 countries from the IQVIA Multinational Integrated Data Analysis System and total and non-high-density lipoprotein (non-HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. Compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. Results From 2008 to 2018, use of LMAs increased from 7468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). An estimated 173 million people used LMAs in 2018. Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and mean total and non-HDL cholesterol concentrations in 2008 versus 2018. Conclusions Since 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non-HDL cholesterol varied considerably.

We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference.Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements.All functional parameters showed no significant difference (P0.05) and were well-correlated (r0.5, P0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient0.9).Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.

Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.

Background The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018. Methods: A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses. Results: Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69–1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12–0.71) per 100 PYFU in 2010–2012 to 1.93 (95% CI 1.36–2.67) in 2016–2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006–2009, and recent syphilis acquisition. Conclusions: An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour.

BACKGROUND Static progressive orthosis is used for the treatment of severe joint contracture after trauma and/or surgery. However, a custom-fabricated static progressive splint would be expensive and labor intensive. Especially, owing to very limited payment under the current Taiwanese National Health Insurance, the incentives to fabricate a patient-specific splint are insufficient for a therapist. To ease splint construction, we introduced three-dimensional (3D)-printed "shark fin"-shaped device works as a static progressive orthosis for the hand rehabilitation. The aim of this study was to describe and demonstrate the newly designed device. METHODS This study included a 46-year male suffered from a left distal radius fracture and underwent open reduction internal fixation and a 23-year male with the right thumb flexor pollicis longus rupture, requiring tendon repair. Both subjects used this "shark fin"-shaped device to stretch for increasing range of motion (ROM) of wrist extension and the thumb. RESULTS The patient receiving ulnar shortening surgery used this device to stretch for increasing ROM of wrist extension. The active ROM of wrist extension improved from 30° to 50°. The other patient with the right thumb flexor pollicis longus rupture suffered from thumb contracture; the ROMs of the metacarpophalangeal (MCP) joint and interphalangeal (IP) joint were 40°-55° and 20°-25°, respectively. After tenolysis surgery, his ROMs of the MCP and IP joints were improved to 10°-35° and 40°-65°, respectively. Following physical therapy by applying the device, his ROMs of the MCP and IP joints were further increased to 0°-40° and 25°-70°, respectively. CONCLUSION Incorporating the "shark fin"-shaped orthosis into hand rehabilitation increased the ROM of wrist extension for a patient with distal radius fracture and improved the ROM of the MCP and IP joints in another patient after tenolysis surgery.

BACKGROUND Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and only a few cases have been reported to date. It has no specific clinical presentations and shows various endoscopic appearances. There is no uniform consensus on its treatment. With the advancement of endoscopic technology, endoscopic treatment has achieved better results in individual case reports of early-stage patients. CASE SUMMARY We report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination, which incidentally found a 25 mm × 20 mm, laterally spreading tumor (LST)-like elevated lesion in the rectum. Therefore, he was referred to our hospital for further endoscopic treatment. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging. And immunopathological staining showed hyperplastic capillaries in the mucosa. Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria, with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm. In addition, immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2. Gene rearrangement results showed positivity for IGH-A, IGH-C, IGK-B, and IGL. Taking all the above findings together, we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomography examination showed no other lesions involved. The patient will be followed by periodic endoscopic observation. CONCLUSION In conclusion, we report a case of rectal MALT with an LST-like appearance treated by endoscopic submucosal dissection. Further studies will be needed to explore the clinical behavior, endoscopic appearance, and treatment of rectal MALT.

Aims Frailty may be found in heart failure patients especially in the elderly and is associated with a poor prognosis. However, assessment of frailty status is time‐consuming, and the electronic frailty indices developed using health records have served as useful surrogates. We hypothesized that an electronic frailty index developed using machine learning can improve short‐term mortality prediction in patients with heart failure. Methods and results This was a retrospective observational study that included patients admitted to nine public hospitals for heart failure from Hong Kong between 2013 and 2017. Age, sex, variables in the modified frailty index, Deyo's Charlson co‐morbidity index (≥2), neutrophil‐to‐lymphocyte ratio (NLR), and prognostic nutritional index at baseline were analysed. Gradient boosting, which is a supervised sequential ensemble learning algorithm with weak prediction submodels (typically decision trees), was applied to predict mortality. Variables were ranked in the order of importance with a total score of 100 and used to build the frailty models. Comparisons were made with decision tree and multivariable logistic regression. A total of 8893 patients (median: age 81, Q1–Q3: 71–87 years old) were included, in whom 9% had 30 day mortality and 17% had 90 day mortality. Prognostic nutritional index, age, and NLR were the most important variables predicting 30 day mortality (importance score: 37.4, 32.1, and 20.5, respectively) and 90 day mortality (importance score: 35.3, 36.3, and 14.6, respectively). Gradient boosting significantly outperformed decision tree and multivariable logistic regression. The area under the curve from a five‐fold cross validation was 0.90 for gradient boosting and 0.87 and 0.86 for decision tree and logistic regression in predicting 30 day mortality. For the prediction of 90 day mortality, the area under the curve was 0.92, 0.89, and 0.86 for gradient boosting, decision tree, and logistic regression, respectively. Conclusions The electronic frailty index based on co‐morbidities, inflammation, and nutrition information can readily predict mortality outcomes. Their predictive performances were significantly improved by gradient boosting techniques.

Qiao Tang, Li Wei, Xiaoqing Liu, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Peng HuDepartment of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 13608338064Email hp_cq@163.comBackground: Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection.Methods: This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12).Results: Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred.Conclusion: Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.Keywords: daclatasvir, hepatitis C virus, ribavirin, sofosbuvir, velpatasvir

Summary Background Inappropriate antibiotic use greatly accelerates antimicrobial resistance. The appropriateness of antibiotic prescriptions is well evaluated, using big observational data, in some high-income countries, whereas the evidence of this appropriateness is scarce in China. We aimed to assess the appropriateness of antibiotic prescriptions in ambulatory care settings in China to inform future antimicrobial stewardship. Methods We used data from the Beijing Data Center for Rational Use of Drugs, which was a national database designed for monitoring rationality of drug use. 139 hospitals that uploaded diagnosis and prescription information were included from 28 provincial-level regions of mainland China. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use by following a published classification scheme. Antibiotic prescription rates for various diagnosis categories and proportions of inappropriate antibiotic prescriptions for different subgroups were estimated. Antibiotic prescribing patterns and proportions of individual antibiotics prescribed for different diagnosis categories were analysed and reported. Findings Between Oct 1, 2014, and April 30, 2018, 18 848 864 (10·9%) of 172 704 117 outpatient visits ended with antibiotic prescriptions. For conditions for which antibiotic use was appropriate, potentially appropriate, and inappropriate, 42·2%, 30·6%, and 7·6% of visits were associated with antibiotic prescriptions, respectively. Of all 18 848 864 antibiotic prescriptions, 9 689 937 (51·4%) were inappropriate, 5 354 224 (28·4%) were potentially appropriate, 2 893 102 (15·3%) were appropriate, and 911 601 (4·8%) could not be linked to any diagnosis. A total of 23 266 494 individual antibiotics were prescribed, of which 18 620 086 (80·0%) were broad-spectrum and the top four most prescribed antibiotics were third-generation cephalosporins (5 056 058 [21·7%]), second-generation cephalosporins (3 823 410 [16·4%]), macrolides (3 554 348 [15·3%]), and fluoroquinolones (3 285 765 [14·1%]). Interpretation Inappropriate antibiotic prescribing was highly prevalent nationwide in China. Over half of the antibiotic prescriptions were inappropriate in secondary-level and tertiary-level hospitals, suggesting an urgent need for outpatient antibiotic stewardship aimed at optimising antibiotic prescribing to achieve the goals set in China's 2016 national action plan to contain antimicrobial resistance. Funding The National Natural Science Foundation of China.