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With the continuous development of digital medicine, minimally invasive precision and safety have become the primary development trends in hepatobiliary surgery. Due to the specificity and complexity of hepatobiliary surgery, traditional preoperative imaging techniques such as computed tomography and magnetic resonance imaging cannot meet the need for identification of fine anatomical regions. Imaging-based three-dimensional (3D) reconstruction, virtual simulation of surgery and 3D printing optimize the surgical plan through preoperative assessment, improving the controllability and safety of intraoperative operations, and in difficult-to-reach areas of the posterior and superior liver, assistive robots reproduce the surgeon’s natural movements with stable cameras, reducing natural vibrations. Electromagnetic navigation in abdominal surgery solves the problem of conventional surgery still relying on direct visual observation or preoperative image assessment. We summarize and compare these recent trends in digital medical solutions for the future development and refinement of digital medicine in hepatobiliary surgery.

Research on the roles of the bacteria in tumor development and progression is a rapidly emerging field. Increasing evidence links bacteria with the modification of the tumor immune microenvironment, which greatly influences the antitumor response. In view of the individual immune effects of various bacteria in various tumors, developing personalized bacteria-modulating therapy may be a key to successful antitumor treatment. This review emphasizes the critical role of the bacteria in immune regulation, including both the tumor bacteria and gut bacteria. Aiming at tumor-related bacteria, we focus on various precise modulation strategies and discuss their impact and potential for tumor suppression. Finally, engineered bacteria with tumor-targeting ability could achieve precise delivery of various payloads into tumors, acting as a precision tool. Therefore, a precise tumor-related bacteria therapy may be a promising approach to suppress the development of tumors, as well as an adjuvant therapy to improve the antitumor efficacy of other approaches. KEY POINTS: • The mini-review updates the knowledge on complex effect of bacteria in TME. • Insight into the interaction and adjustment of bacteria in gut for TME. • Prospects and limitations of bacteria-related personalized therapy in the clinical anticancer therapy.

BACKGROUND Chondroblastoma (CB) is an intermediate tumor of cartilage origin. CB involving the sacrum is a very rare pathology. CASE SUMMARY A 17-year-old male with sacral CB was diagnosed as CB during the first surgery, and 18 mo later, the tumor recurred and a second surgery was performed with the same pathology result of CB. CONCLUSION We recommend complete removal of the tumor in a timely manner, provided that surgical conditions are met. At the same time, other diseases should be carefully differentiated in terms of imaging or pathological features so as to avoid erroneous diagnostic conclusions.

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity., Using data-driven epidemiological modelling, Yu et al. estimate that, even with increasing vaccine availability, China will have to maintain stringent non-pharmaceutical interventions for at least a year to prevent new widespread outbreaks of COVID-19.

BACKGROUND AND AIM Gastrointestinal submucosal tumors (SMTs) can be removed by submucosal tunneling endoscopic resection (STER). However, limited studies have evaluated STER for the removal of multiple upper gastrointestinal SMTs. The aim of this study was to evaluate the feasibility and outcomes of STER in the treatment of multiple upper gastrointestinal SMTs. METHODS From January 2011 to April 2020, the cases of patients with multiple upper gastrointestinal SMTs undergoing STER were retrospectively analyzed. Variables of clinicopathological characteristics, major adverse events (mAEs), and follow up were collected and analyzed. RESULTS Submucosal tunneling endoscopic resection was performed in 54 patients (48 male and 6 female patients) with 120 SMTs. Forty-four patients had two tumors, eight patients had three tumors, and two patients had four tumors. The median size of each patient was 1.8 cm (range 0.7 to 3.5 cm). Forty-five patients had tumors removed by one tunnel, and nine patients by two tunnels. The median procedure time was 50 min (range 14 to 120 min), and the mAE rate was 16.7% (9/54). No significant differences were found between patients with two tumors and those with > 2 tumors in terms of tunnel length, hospital stay, procedure time, and mAEs (all P > 0.05). In addition, patients with two tunnels had procedure time, hospital stay, and mAE rates comparable with those with one tunnel (all P > 0.05). No local recurrence or distant metastasis occurred during a median follow up of 64 months. CONCLUSIONS Submucosal tunneling endoscopic resection is a safe and effective technique for the resection of multiple upper gastrointestinal SMTs.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.

Background: Hyperfibrinolysis and pro/anti-inflammatory imbalance usually occur in the early stage of severe burns. Soluble urokinase-type plasminogen activator receptor (suPAR) is involved in fibrinolysis and inflammation. To date, the levels of circulating suPAR in non-survivors with severe burns remain unknown. This study aimed to investigate the early association between circulating suPAR levels and biomarkers of fibrinolysis, pro/anti-inflammatory, and prognosis. Methods: Sixty-four consecutive Chinese patients with severe burns and 26 healthy volunteers were enrolled in a prospective observational cohort. Clinical characteristics and laboratory data were collected prospectively. Blood samples were collected at 48 h post-burn, and suPAR and biomarkers of pro/anti-inflammatory and fibrinolysis were detected by enzyme-linked immunosorbent assays. Important indicators between non-survivors and survivors were compared. Linear regression analysis was performed to screen variables associated with suPAR. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were performed to evaluate the prognostic value of suPAR. Result: Compared with the control group, the circulating suPAR levels in the survivors (P

Study Design: Retrospective pooled analysis of individual patient data. Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

BACKGROUND To explore the vitamin D status with its demographic and lifestyle factors including dietary, supplementation, and physical activity in 0-5 years old children. METHODS This was a large population-based cross-sectional multicentre study in which the children were recruited from 12 Children's Health Care Centers by a stratified cluster random-sampling method in 10 cities in Jiangsu Province, China. RESULTS A total number of 5289 children were investigated. The prevalence of vitamin D deficiency was 30.1%. The concentration of 25 hydroxyvitamin D was 64.0 (46.3-83.0) nmol mL-1 after adjustment for covariates. Children with higher risk of vitamin D deficiency were more likely to be at older age, girls, survey conducted in spring, location in southern Jiangsu province, residence in urban, outdoor activity 400 IU day-1 (all p 150.0 g day-1 , milk consumption

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts., Detailed knowledge of COVID-19 epidemiology is needed to inform public health responses. Here, the authors use large-scale contact tracing data to provide empirical estimates of key parameters, and show that susceptibility increases with age but transmissibility does not vary significantly.

Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model. Methods and Results: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1β/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine–triggered mitochondrial dysfunction and fibrosis. Moreover, β-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake. Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting β-hydroxybutyrate abundance.

By summarizing the recent literatures on brain mechanisms with acupuncture intervention based on blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging (fMRI), the BOLD-fMRI examination and analysis methods, the points to be acupunctured, the corresponding meridian activation regions, the specific intensity range, functions and indications of the acupoints, the manifestation of ‘bi-directional regulation’ characteristics, fMRI performance of chronergy, laterality and needling qi of acupuncture were reviewed to provide the ideas for future research in this area.

Objective There is strong evidence that the body composition can affect the progression-free survival (PFS) and overall survival (OS) in patients with a variety of cancers. The main objective of this study was to investigate the effect of body composition on the prognosis of patients with advanced gastrointestinal and colorectal cancers who received first-line palliative chemotherapy. Methods Patients who were newly-diagnosed with advanced gastrointestinal or colorectal cancer and received standard first-line palliative chemotherapy from January 2017 to December 2018 were included in this retrospective study. An analysis of computed tomography images was performed to determine the skeletal muscle index (SMI), which reflects the skeletal muscle mass and skeletal muscle density (SMD) related to muscle strength. A Kaplan-Meier survival analysis and log-rank test were used to compare the survival relationships among groups stratified by the SMI, and a Cox proportional hazard model was used for a multivariate analysis. Results A total of 108 patients met the inclusion criteria, including 41 cases of gastric cancer, 46 cases of left colorectal cancer, and 21 cases of right colon cancer. In patients with gastric cancer, the OS of women was significantly shorter than that of men. The OS of patients with a low SMI, low SMD, and low phase angle (PA) was significantly shorter than that of patients with high values (P ≤ 0.05). In the multivariate analysis, the SMD was significantly associated with the patients' long-term survival [Hazard Ratio (HR) = 0.904, 95% CI: 0.840~0.974, P = 0.008]. For patients with a low SMI and PA, the PFS was significantly shorter than that of patients with high values (P ≤ 0.05). In patients with left colon cancer, the PA and SMD were both independent risk factors for a poorer long-term prognosis (HR = 0.375, 95% CI: = 0.167~0.840, P = 0.017; HR = 0.887, 95% CI: 0.824~0.954, P = 0.001). Among right colon cancer patients, the PFS and OS of those with a low SMD were significantly lower than those for patients with high values (P ≤ 0.05). Conclusion The PA is an independent risk factor for the OS of left colon cancer patients; the SMD is an independent risk factor for the survival of patients with gastric cancer, left colon cancer, and right colon cancer.

Purpose To investigate the impact of diabetic peripheral neuropathy and its severity on the threshold of sciatic nerve electrical stimulation in diabetic patients. Patients and Methods The case-control study included 60 patients that were divided into non-diabetic patients (control group, n = 26) and diabetic patients (diabetes group, n = 34). All the patients who were scheduled for lower leg, foot, and ankle surgery received a popliteal sciatic nerve block. We recorded the minimum current required to produce motor activity of the sciatic nerve during ultrasound-guided popliteal sciatic nerve block. Results Among the 60 patients, the sciatic nerve innervated muscle contractile response was successfully elicited in 57 patients (dorsiflexion of foot, plantar flexion, foot valgus or adduction, toe flexion, etc.) under electric stimulation. We failed to elicit the motor response in three patients with diabetic peripheral neuropathy, even when the stimulation current was 3 mA. The average electrical stimulation threshold (1.0 ± 0.7 mA) in the diabetes group was significantly higher than that of the control group (0.4 ± 0.1 mA). Diabetic patients with peripheral neuropathy had a higher electrical stimulation threshold (1.2 ± 0.7 mA) than patients without peripheral neuropathy (0.4 ± 0.1 mA). Furthermore, the electrical stimulation threshold of the sciatic nerve in diabetic patients had a linear dependence on the Toronto Clinical Scoring System (TCSS) peripheral neuropathy score (electrical stimulation threshold [in mA] = 0.125 TCSS score) (P < 0.001). Conclusion The threshold of electrical stimulation to elicit a motor response of the sciatic nerve was increased in diabetic patients, and the threshold of electrical stimulation of the sciatic nerve increased with the severity of diabetic nerve dysfunction.

Understanding and controlling the charge transfer processes of two-dimensional (2D) materials are fundamental for the optimized device performance based on 2D semiconductors and heterostructures. The charge transfer rate is very robust in transition metal disulfide (TMD) heterostructures with type II band alignments, which can be manipulated by intercalating a dielectric layer like hBN to isolate the donor and acceptor monolayers. This study shows that there is an alternative way to change the electron transfer and recombination rates in the case of nLMoS2/mLWSe2 multilayer heterostructures, where the donor-acceptor distance is maintained, but the rate of electron transfer is strongly layer dependent and shows asymmetry for the layer number of donor and acceptor monolayers. Especially, the 1LMoS2/2LWSe2 heterostructure slows electron transfer and charge recombination rates ∼2.3 and ∼12 times that of the 1LMoS2/1LWSe2 heterostructure, respectively, which have been competitive with that in the 1LMoS2/hBN/1LWSe2 heterostructure. From an application perspective, the noninterfacial electron transfer in which photogenerated electrons should across more than one atomically thin layer is not favorable due to the built-in electric field established by the initial interfacial electron transfer.

Objectives. To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics. Methods and Results. Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent. Conclusion. This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

Background Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

A case of the absorption of corona virus disease 2019 (COVID-19) promoted by professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" is introduced. A female patient suffered from COVID-19, 64 years old, had been treated with acupuncture and Chinese herb granules for 10 days on the base of the oral administration of moxifloxacin. In the re-examination, the chest CT image indicated that the absorption of COVID-19 was obvious as compared with before, the nucleic acid test of novel corona virus was negative and the patient narrated no obvious discomfort. Acupuncture therapy plays its active adjuvant effect in the whole process of the treatment of COVID-19.

The moisture extraction rate (MER) and energy efficiency of domestic gas clothes dryers, heat-pump clothes dryers and electric clothes dryers were assessed. The assessment was performed with regard to five indices: the MER, specific MER, specific thermal energy consumption for dehumidification (mSPC), energy efficiency (ηt) and primary energy efficiency (η1). The effects of the dry mass of clothes (mBD) and the ambient temperature on the performance of the clothes dryers were evaluated. The experiments were divided into two parts. In the first part, the ambient temperature was 20°C, and mBD was set as 1.5, 2.5, 3.5, 4.5 and 6 kg. In the second part, mBD was 3.5 kg, and the performance of the dryers was tested at ambient temperatures of 5, 7.5, 10, 12.5, 15 and 20°C. The experimental results indicated that the gas dryer had the highest MER the heat-pump dryer had the best performance with regard to energy conservation and all three types of dryers had a higher MER and energy efficiency when the ambient temperature increased. The performance of the gas dryer was lower than that of heat-pump dryer when the temperature was 20°C. But when the temperature was

Fiber transfer box is a box containing fiber ports which transfer optical signals for telecommunication networks. It’s hard to check and record the status of hundreds of ports using man power. This paper proposes an intelligent recognition and localization system for fiber transfer box. Pictures of ports are treated and classified with Support Vector Machine (SVM) and Deep learning algorithm. It can identify the status of all ports in the fiber transfer box and recognize the writing letter for each layer. First, the image is converted to binary one by threshold of the Cr channel. A SVM classifier is used to identify the Red-Hat ports by HOG features. Second, an adaptive chessboard segmentation algorithm is designed for segmentation of all ports and character area. In order to improve the identification accuracy, an eleven-layer Convolution Neural Network (CNN) is trained and used to further identify the ports which have not been classified correctly by SVM. Letters are extracted and positioned by using YOLOv3-tiny network. Experiments show that the method achieves great accuracy and efficiency for a variety of scenes on mobile devices.

Objective: To investigate the effect of small needle-knife therapy in people with painful knee osteoarthritis. Design: Pilot randomised, controlled trial. Setting: Rehabilitation hospital. Subjects: In-patients with osteo-arthritis of the knee. Interventions: Either 1 to 3 small needle-knife treatments over seven days or oral Celecoxib. All patients stayed in hospital three weeks, receiving the same mobility-focused rehabilitation. Measures: Oxford Knee Score (OKS), gait speed and kinematics were recorded at baseline, at three weeks (discharge) and at three-months (OKS only). Withdrawal from the study, and adverse events associated with the small needle knife therapy were recorded. Results: 83 patients were randomized: 44 into the control group, of whom 10 were lost by three weeks and 12 at 3 months; 39 into the experimental group of whom eight were lost at three weeks and three months. The mean (SE) OKS scores at baseline were Control 35.86 (1.05), Exp 38.38 (0.99); at three weeks 26.64 (0.97) and 21.94 (1.23); and at three months 25.83 (0.91) and 20.48 (1.14) The mean (SE) gait speed at baseline was 1.07 (0.03) m/sec (Control) and 0.98 (0.03), and at three weeks was 1.14 (0.03) and 1.12 (0.03) ( P < 0.05). Linear mixed model statistical analysis showed that the improvements in the experimental group were statistically significant for total OKS score at discharge and three months Conclusions: Small needle-knife therapy added to standard therapy for patients with knee osteoarthritis, was acceptable, safe and reduced pain and improved global function on the Oxford Knee Score. Further research is warranted.

The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy. From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes. The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%. The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable.

Background: Perihematomal edema (PHE) is a major threat leading to poor functional outcomes after intracerebral hemorrhage (ICH). TIMP-2 is considered to participate in the formation of PHE after ICH by antagonizing the damaging effects of MMP-2. In the early study, the polymorphisms of TIMP-2 rs8179090 have shown to influence the expression of TIMP-2. Objective: To prove that the severity of PHE was different in ICH patients with different TIMP-2 rs8179090 genotypes. Methods: In this prospective study, 130 hypertensive ICH patients were enrolled. The poly phisms of rs8179090 in TIMP-2 were determined. The hematoma volume and PHE volume were measured by computed tomography (CT) scan immediately after the onset of ICH, and were measured again one week and two weeks after the onset. Then, the comparison of TIMP-2 rs8179090 genotypes was made. Result: TIMP-2-418 position (rs8179090) had two genotypes in the studied population, GC and GG. Patients with the GC genotype developed more severe PHE, with a higher incidence of delayed cerebral edema in cerebral hemorrhage than those with the GG genotype. Conclusion: We have found that the GC genotype group may develop more severe PHE, with an increased incidence of delayed cerebral edema in cerebral hemorrhage.

BACKGROUND Previous studies have shown that patients with diabetes mellitus (DM) respond poorly to clopidogrel treatment. AIM To systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM. METHODS PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched from 1980 on 27 June 2019 to identify relevant randomized controlled trials that compared the effect of a combination of clopidogrel and aspirin with aspirin alone. A random-effects meta-analysis was used to estimate the hazard ratio (HR) and its 95% confidence interval (CI). Sensitivity analysis was performed using a fixed-effect model. The I2 statistic was used to evaluate the heterogeneity of the study data. RESULTS Six randomized controlled trials, comprising 43352 participants (13491 with and 29861 without DM) who had received antiplatelet therapy for ≥ 3 mo, were included in the meta-analysis. Compared with aspirin alone, a combination of clopidogrel and aspirin significantly reduced the risk of any cardiovascular event in patients without DM (HR = 0.78, 95%CI: 0.71–0.86, P < 0.001; I2 = 23%, P = 0.26). Clopidogrel plus aspirin also significantly reduced cardiovascular risk in patients with DM, although the effect was smaller (HR = 0.89, 95%CI: 0.81–0.99, P = 0.030; I2 = 0%, P = 0.74). Nevertheless, there was no significant difference in the efficacy of clopidogrel at reducing the risk of cardiovascular events in patients with DM vs those without (P for interaction = 0.062). CONCLUSION Thus, the present study shows that the addition of clopidogrel to aspirin significantly lowers cardiovascular risk in patients with or without DM who have experienced ischemic cardiovascular disease. The beneficial effect of the addition of clopidogrel to aspirin for patients with DM was lower than that in patients without DM, although the modifying effect of DM did not reach significance.

Liver malignancies include primary and metastatic tumors. Limited progress has been achieved in improving the survival rate of patients with advanced stage liver cancer and who are unsuitable for surgery. Apart from surgery, chemoradiotherapy, trans-arterial chemoembolization and radiofrequency ablation, a novel therapeutic modality is needed for the clinical treatment of liver cancer. Photodynamic therapy (PDT) is a novel strategy for treating patients with advanced cancers; it uses a light-triggered cytotoxic photosensitizer and a laser light. PDT provides patients with a potential treatment approach with minimal invasion and low toxicity, that is, the whole course of treatment is painless, harmless, and repeatable. Therefore, PDT has been considered an effective palliative treatment for advanced liver cancers. To date, PDT has been used to treat hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma and liver metastases. Clinical outcomes reveal that PDT can be considered a promising treatment modality for all liver cancers to improve the quality and quantity of life of patients. Despite the advances achieved with this approach, several challenges still impede the application of PDT to liver malignancies. In this review, we focus on the recent advancements and discuss the future prospects of PDT in treating liver malignancies.

Objectives The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics–based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. Background A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. Methods A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics–based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and “gray zone” lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. Results Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p 0.80; p = 0.397) and in patients with “gray zone” versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and Conclusions This novel computational fluid dynamics–based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

Background The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P, Increase in overall survival of lymphoma from 1996 to 2015.

BACKGROUND Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies investigating alternative therapies are plenty. Nevertheless, no study has comprehensively analyzed these therapies from different perspectives. AIM To summarize the current status of alternative transplantation therapies for OLT and to support future research. METHODS A systematic literature search was performed using PubMed, Cochrane Library and EMBASE for articles published between January 2010 and 2018, using the following MeSH terms: [(liver transplantation) AND cell] OR [(liver transplantation) AND differentiation] OR [(liver transplantation) AND organoid] OR [(liver transplantation) AND xenotransplantation]. Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation. Among them, we selected articles including in vivo transplantation. RESULTS A total of 89 studies were selected. There are three principle forms of treatment for liver failure: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Xeno-organ transplantation was covered in 14 articles, scaffold-based transplantation was discussed in 22 articles, and cell transplantation was discussed in 53 articles. Various types of alternative therapies were discussed: Organ liver, 25 articles; adult hepatocytes, 31 articles; fetal hepatocytes, three articles; mesenchymal stem cells (MSCs), 25 articles; embryonic stem cells, one article; and induced pluripotent stem cells, three articles and other sources. Clinical applications were discussed in 12 studies: Cell transplantation using hepatocytes in four studies, five studies using umbilical cord-derived MSCs, three studies using bone marrow-derived MSCs, and two studies using hematopoietic stem cells. CONCLUSION The clinical applications are present only for cell transplantation. Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations, which warrants future research to find relevant clinical applications.

To evaluate the outcomes of refractory/relapsed cHL patients after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in Beijing Cancer hospital and to identify the prognostic risk factors. We retrospectively analyzed 115 relapsed/refractory cHL patients who accepted HDCT and ASCT in our cancer center and had complete follow-up data from April 2000 to May 2017. Ages of these 115 patients at ASCT ranged from 14 to 63 (median age 28). Forty-four (38.3%) patients achieved CR and 50 (43.5%) patients achieved PR before ASCT. Thirty-seven (48.7%) patients of those 76 patients who did PET-CT before ASCT had negative PET-CT scans. The median follow-up time was 72 months. A total of 23 patients died in our study. The 5-year OS and PFS rates of all patients after ASCT were 78.7% and 53%, respectively. The 5-year OS rates after ASCT of patients who were in CR or PR or less than PR status before ASCT were 92.8%, 68.2%, and 76.2%, respectively (log-rank = 2.913, p = 0.233). And their 5-year PFS rates after ASCT were 69.2%, 54.2%, and 18.5%, respectively (log-rank = 13.615, p = 0.001). Univariate analysis revealed that ECOG (p = 0.010; hazard ratio = 1.578), disease status before ASCT (CR: p = 0.001; hazard ratio = 0.227) and after ASCT (CR: p < 0.001; hazard ratio = 0.154), and PET-CT results after ASCT (p = 0.023; hazard ratio = 0.438) significantly impact patients' PFS while number of pretransplant salvage chemotherapy (p = 0.037; hazard ratio = 2.521), radiotherapy (p = 0.046; hazard ratio = 0.423), and disease status after ASCT (CR: p = 0.010; hazard ratio = 0.197) significantly affected patients' OS. Multivariate analysis shown only disease status before ASCT (p = 0.002) had significant impact on PFS and disease status after ASCT (p = 0.021) had significant impact on OS. R/R HL patients can still obtain long-term PFS after HDCT and ASCT and disease status before ASCT was the most significant prognostic factor for PFS.

In this paper, we investigated the performance of an n-type tin-oxide (SnOx) thin film transistor (TFT) by experiments and simulation. The fabricated SnOx TFT device by oxygen plasma treatment on the channel exhibited n-type conduction with an on/off current ratio of 4.4×104, a high field-effect mobility of 18.5 cm2/V.s and a threshold swing of 405 mV/decade, which could be attributed to the excess reacted oxygen incorporated to the channel to form the oxygen-rich n-type SnOx. Furthermore, a TCAD simulation based on the n-type SnOx TFT device was performed by fitting the experimental data to investigate the effect of the channel traps on the device performance, indicating that performance enhancements were further achieved by suppressing the density of channel traps. In addition, the n-type SnOx TFT device exhibited high stability upon illumination with visible light. The results show that the n-type SnOx TFT device by channel plasma processing has considerable potential for next-generation high-performance display application.

Data on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD.This was a large population-based multicenter study in which the representative children aged 0-5 years were recruited from 13 Children's Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson's correlation and further tested using partial correlation in the additive model.A total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r=0.711, P0.001; r=0.727, P0.001; r=-0.318, P0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2kg, but started to gain slowlyand even decreased when the weight was over 21.2kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (β=-47.45, 95%CI=-85.07, -9.83, P=0.013).Adiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.

Acute pancreatitis is a sudden inflammation and only last for a short time, but might lead to a life-threatening emergency. Traditional drug therapy is an essential supportive method for acute pancreatitis treatment, yet, failed to achieve satisfactory therapeutic outcomes. To date, it is still challenging to develop therapeutic medicine to redress the intricate microenvironment promptly in the inflamed pancreas, and more importantly, avoid multi-organ failure. The understanding of the acute pancreatitis, including the causes, mechanism, and severity judgment, could help the scientists bring up more effective intervention and treatment strategies. New formulation approaches have been investigated to precisely deliver therapeutics to inflammatory lesions in the pancreas, and some even could directly attenuate the pancreatic damages. In this review, we will briefly introduce the involved pathogenesis and underlying mechanisms of acute pancreatitis, as well as the traditional Chinese medicine and the new drug option. Most of all, we will summarize the drug delivery strategies to reduce inflammation and potentially prevent the further development of pancreatitis, with an emphasis on the bifunctional nanoparticles that act as both drug delivery carriers and therapeutics.

The Multicast Routing Algorithm (SDSMR) based on state distributed sensor network solves the problem of limiting multicast routing in the wireless sensor network due to parameters such as energy saving ratio and throughput. There are three kinds of nodes in the algorithm: cluster head node (CH), core node (CNs) and sensor node (SNs). The CH node performs topology control routing and monitors the energy state of the sns. The CNS stores multicast routing state information to minimize routing complexity when a link fails. The SNs participates in multicast routing supported by the core node network. It saves energy consumption of the CNs and improves the performance of the entire network. The simulation results show that in SDSMR algorithm, HGMR algorithm and DCAMEM algorithm, SDSMR algorithm can effectively shorten the delay time and improve the energy saving rate and throughput rate.

CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin’s lymphoma (B-NHL). However, comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75–5 × 105/kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1 × 106/kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process., Graphical Abstract

Backgroud : CD19-directed chimeric antigen receptor T (CAR-T) cell therapy has shown great promise for cure of relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). Previous studies reported that 4-1BB-based CD19 CAR-T was more beneficial for the clinical outcomes than CD28-based CAR-T, especially lower rates of severe adverse events. However, the median progression-free survival (mPFS) of 4-1BB-based product Kymriah was shorter than that of the CD28-based Yescarta (2.9 v.s. 5.9 months), suggesting that the long-term effectiveness of Kymriah was limited. Thus, a safe and durable 4-1BB-based CD19 CAR-T needs to be developed. Methods Here we presented a CD19 CAR-T (named IM19) with FMC63 scFv, 4-1BB and CD3ζ intracellular domain, which was manufactured into a memory T-enriched formulation and launched a clinical trial for treatemt of r/r B-NHL. The clinical outcomes of IM19 were evaluated in 22 r/r B-NHL patients in a Phase I/II trial with dose-escalation investigation (5×105, 1×106 and 3×106/kg). Results All patients received a single infusion of IM19 after 3-day conditional regimen. Cytokine release syndrome (CRS) occurred in 13 patients (59%), with 54.5% of grade 1–2 and 4.5% of grade 3, whereas Kymriah led to 22% of > grade 3 CRS. Only one patient showed > grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). At 6 months, the overall response rate was 47.62%, and the complete response rate was 42.86%. The mPFS of IM19 achieved 9 months and the 1-year overall survival rate was 78%. Conclusions These results demonstrated the safety and durable efficacy of IM19 with FMC63 scFv, 4-1BB and CD3ζ intracellular domain, that is promising for further development and clinical investigation. Trial registration : The registration date of the clinical trial is May 17, 2018(17/05/2018) and the trial registration numbers is NCT03528421.

SummaryBackgroundHundreds of millions of doses of COVID-19 vaccines have been administered globally, but progress in vaccination varies considerably between countries. We aim to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines.MethodsWe conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 23 October 2021. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries’ target populations according to their national immunization program policies.FindingsUse of both mRNA and adenovirus vectored vaccines was the most commonly used COVID-19 vaccines formulary in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (176 countries). Almost all countries (98.3%, 173/176) have authorized vaccines for the general public, with 53.4% (94/176) targeting individuals over 12 years and 33.0% (58/176) targeting those ≥18 years. Forty-one and sixty-seven countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 116.5 doses administered per 100 target population, although with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0% to more than 95.0% of country target populations, and numbers of doses administered ranged from 0 to 239.6 per 100 target population. Doses administered per 100 total population correlated with healthcare access and quality index (R2 = 0.58), socio-demographic index (R2 = 0.56), and GDP per capita (R2 = 0.65). At least 5.54 billion doses will be required to complete interim vaccination programs – 4.65 billion for primary immunization and 0.89 billion for additional/booster programs. Globally, 0.84 and 0.96 dose per individual in the target population are needed for primary immunization and additional/booster programs, respectively.InterpretationThere is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.FundingKey Program of the National Natural Science Foundation of China, the US National Institutes of Health.Research in contextEvidence before this studyWe searched PubMed for articles in any language published up to October 21, 2021, using the following search terms: (“COVID-19” OR “SARS-CoV-2”) AND (“vaccination” OR “vaccine”) AND (“inequalit*” OR “inequity” OR “disparit*” OR “heterogeneity”). We also searched for dashboards associated with vaccine rollout from public websites. We identified several studies on tracking global inequalities of vaccine access, one of which constructed a COVID-19 vaccine dashboard (Our World in Data), and another that explored disparities in COVID-19 vaccination among different-income countries. However, we found no studies that depict global COVID-19 vaccination policies country-by-country and estimate demand for vaccine necessary to completely vaccinate countries’ designated target populations.Added value of this studyTo our knowledge, our study provides the most recent picture of COVID-19 vaccination campaigns, focusing on global vaccination policy and target-population demand. We found a diverse portfolio of vaccines in five technical platforms being administered globally, with 173 countries having authorized administration of vaccines to the general public in various age groups. We observed inter-region and inter-country heterogeneity in one-or-more-dose and full-dose coverage; countries with higher socio-demographic or health resource-related levels had higher coverage. We estimated dose-level demand for completing primary immunization programs and additional/booster dose programs separately.Implications of all the available evidenceWorldwide disparity and inequity of vaccine rollout implies that susceptibility among unvaccinated populations in some countries may impede or reverse pandemic control, especially in face of the emergence of variants and the dilemma of waning antibodies. Our findings suggest that global-level responses to the pandemic - financially, politically, and technically - are needed to overcome complex challenges that lie ahead.

Background: Lipid metabolism disorders play a key role in the pathogenesis of squamous cell carcinoma (SqCC). Herein we used lipidomics to study the tissue lipid profiles of 40 patients with SqCC. Methods: Lipidomics, based on ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry, was applied to identify altered lipid metabolites between tumor and adjacent noninvolved tissues (ANIT), and partial least squares-discriminant analysis model facilitated the identification of differentially abundant lipids. The area under the receiver operator characteristic curve and variable importance in projection scores of the aforementioned model were calculated to select lipid profiles. Metabolic pathway analyses were completed using Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst. Results: Differences in lipid profiles were found between tumor and ANIT, early- and advanced-stage SqCC, and positive and negative lymph node metastases. The lipid profile panel was composed of five lipids—PC(44:4), diacylglycerol(36:5), sphingomyelin(d18:1/20:0), phosphatidylinositol(46:7), and HexCer-AP(t8:0/32:2 + O)—and could effectively differentiate between tumor and ANIT. Further, pathway analyses revealed alterations in several lipid metabolism pathways, including glycerophospholipid metabolism, glycosylphosphatidylinositol anchor biosynthesis, linoleic acid metabolism, glycerolipid metabolism, and sphingolipid metabolism. Conclusion: Our data revealed several changes in the tissue lipid profiles of patients with SqCC; moreover, we identified a lipid profile panel that could effectually distinguish tumor tissues from ANIT. We believe that our results provide new insights into the biological behavior of lung SqCC.

Supplemental Digital Content is available in the text., Background and Purpose: Neuronal pyroptosis is a type of regulated cell death triggered by proinflammatory signals. CCR5 (C-C chemokine receptor 5)-mediated inflammation is involved in the pathology of various neurological diseases. This study investigated the impact of CCR5 activation on neuronal pyroptosis and the underlying mechanism involving cAMP-dependent PKA (protein kinase A)/CREB (cAMP response element binding)/NLRP1 (nucleotide-binding domain leucine-rich repeat pyrin domain containing 1) pathway after experimental intracerebral hemorrhage (ICH). Methods: A total of 194 adult male CD1 mice were used. ICH was induced by autologous whole blood injection. Maraviroc (MVC)—a selective antagonist of CCR5—was administered intranasally 1 hour after ICH. To elucidate the underlying mechanism, a specific CREB inhibitor, 666-15, was administered intracerebroventricularly before MVC administration in ICH mice. In a set of naive mice, rCCL5 (recombinant chemokine ligand 5) and selective PKA activator, 8-Bromo-cAMP, were administered intracerebroventricularly. Short- and long-term neurobehavioral assessments, Western blot, Fluoro-Jade C, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunofluorescence staining were performed. Results: The brain expression of CCL5 (chemokine ligand 5), CCR5, PKA-Cα (protein kinase A-Cα), p-CREB (phospho-cAMP response element binding), and NLRP1 was increased, peaking at 24 hours after ICH. CCR5 was expressed on neurons, microglia, and astrocytes. MVC improved the short- and long-term neurobehavioral deficits and decreased neuronal pyroptosis in ipsilateral brain tissues at 24 hours after ICH, which were accompanied by increased PKA-Cα and p-CREB expression, and decreased expression of NLRP1, ASC (apoptosis-associated speck-like protein containing a CARD), C-caspase-1, GSDMD (gasdermin D), and IL (interleukin)-1β/IL-18. Such effects of MVC were abolished by 666-15. At 24 hours after injection in naive mice, rCCL5 induced neurological deficits, decreased PKA-Cα and p-CREB expression in the brain, and upregulated NLRP1, ASC, C-caspase-1, N-GSDMD, and IL-1β/IL-18 expression. Those effects of rCCL5 were reversed by 8-Bromo-cAMP. Conclusions: CCR5 activation promoted neuronal pyroptosis and neurological deficits after ICH in mice, partially through the CCR5/PKA/CREB/NLRP1 signaling pathway. CCR5 inhibition with MVC may provide a promising therapeutic approach in managing patients with ICH.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 85% of individuals aged ⩾12 years have been vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while children aged 0–11 years are currently not eligible for vaccination (as of September 2021). The aim of this work is to assess whether the importation of Delta variant infections will shift the COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate the epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years (as of September 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could lead to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the currently eligible age groups. The symptomatic SARS-CoV-2 infections and hospitalisation are projected to shift towards children and young adolescents, with 13% of symptomatic infections and 30% of hospitalisations occurring in those aged 0–11 years. Extending the vaccination roll-out to include children aged 3–11 years is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively), but would have a low impact on protecting infants (aged 0–2 years). Our findings highlight the need to strengthen vaccination efforts by simultaneously extending the target population and elevating vaccine effectiveness. Author summary Older age groups have the highest risk of severe illness and fatality from SARS-CoV-2 infection. While the vaccination coverage in China is highly skewed towards older age groups. No study has quantified to what extent the spread of Delta variant infections and lack of vaccination in younger age groups will shift the COVID-19 burden towards younger age groups and how this will affect the return to normal. To this end, we developed an age-structured transmission model to mimic the epidemics triggered by imported Delta variant infections in China. In the context of the vaccination programme targeting individuals aged ≥12 years as of September 2021, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections would lead to substantial disease burden, which will shift towards the 0–11-year age group. Extending the vaccination to children aged 3–11 years, for whom the currently available vaccines have been licensed, is projected to dramatically decrease symptomatic infections and hospitalisations within this age group but would have a low impact in protecting infants aged 0–2 years. This study highlights the value of extending vaccination to children aged 3–11 years and protecting infants 0–2 years by vaccinating their contacts.

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts.Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF.Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.

Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section and (d) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; CDSR (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.

Despite the increasing popularity of green finance and sustainable investment in the field of Sustainable Development Goals (SDGs), very few studies have investigated the effect of green finance dimensions on the sustainable performance of banks. Therefore, this study attempts to examine the dimensions of green finance and their effects on the sustainability performance of financial institutions in developing economies such as Bangladesh. The study also depicts the level of green financing adoption among the banks and non-bank financial institutions in the country between 2015 and 2020. Considering the nature of the dataset, the structural equation modeling technique was employed in this study to fulfil the research objectives. Amongst banks and non-bank financial institutions, the study highlighted private commercial banks as being the highest contributor to green financing, accounting for 78.12% of the total green financing in Bangladesh. In addition, the empirical findings revealed that the dimensions of green finance are related to the economic, social, and environmental aspects of the SDGs. Furthermore, empirical findings indicated that the dimensions of green finance—social, economic, and environmental—have a strong positive effect on the sustainability performance of banks. The study also discovered that approximately 95% of bankers identify green financing as an essential element in the short- and long-term development of banking strategies in Bangladesh. Consequently, this study adds to the body of knowledge on green finance development and the sustainability performance of banks and financial institutions in emerging economies such as Bangladesh. Therefore, major managerial policy implications are discussed.

BackgroundCurrently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC).MethodsLiterature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis.ResultsFifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables.ConclusionsThese data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.

This study aims to identify the COVID-19 impact on the green banking activities including green financing of banks and non-bank financial institutions (NBFIs) during the pandemic. Besides, this study also reveals the in-house environmental management of banks and NBFIs during the COVID-19 outbreak. To analyze the impact of the pandemic on green banking activities, secondary data were obtained from the quarterly and annual reports of Bangladesh Bank (BB) on green banking activities, annual reports and websites of the sample banks and NBFIs in Bangladesh for the period 2020–2019. The study utilized descriptive statistics, relative percentage changes, and varying tables and graphs to analyze the obtained secondary data. Consequently, the empirical findings revealed that, compared to the pre-pandemic period, banks’ total green financing rose by 7.26% during the pandemic, while total green financing of NBFIs plummeted by 18.53% during the same period. In addition, the category-wise results indicate that green financing of the private commercial banks (PCBs) decreased by 11% during the COVID-19 pandemic, contrasting the 56.54% increase witnessed by the state-owned commercial banks (SOCBs) during the same period. Interestingly, our findings showed that green financing of foreign-owned commercial banks (FCBs) during the pandemic increased by 78.69% in 2020 compared to 2019. During the same period, BB refinancing scheme for green products/initiatives of banks and NBFIs grew by 76.97%. The results further showed that the PCBs and FCBs’ in-house environmental management expanded during the outbreak except for the number of solar-powered ATM booths, which dropped by 68.25% for PCBs and 9.09% for FCBs. On the other hand, SOCBs’ in-house environmental management grew during the pandemic. Furthermore, the results indicate that the Bangladeshi banks’ automation towards green banking were satisfactory during the pandemic. Therefore, major policy implications for the green economic recovery of the government, BB, and mangers of the banks and financial institutions in emerging economies like Bangladesh were discussed.

ImportanceWhether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults ≥60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults≥60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses.InterventionsTwo formulations (3 μg, and 6 μg) were used in phase 1 trial, and an additional formulation of 1.5 μg was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose.Main outcomes and measuresGeometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination.ResultsNeutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 μg group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity.Conclusion and relevanceNeutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults.Trial registrationClinicalTrials.gov(NCT04383574).

Background Serofast status is challenging to interpret in clinical work, and distinguishing active syphilis in serofast patients can provide a reference for clinical diagnosis and treatment. However, effective serologic markers for active syphilis are still lacking. Objectives We aimed to explore the possibility of nontreponemal IgM antibodies in distinguishing active syphilis in serofast patients. Methods A total of 1501 clinical serum samples were collected from 301 serofast patients, and nontreponemal IgM antibodies were detected by chemiluminescence immunoassay. Results The results showed that a total of 29 samples (9.63%) of 301 serofast patients were positive for nontreponemal IgM antibodies, and our limited follow-up data showed that 66.67% (2/3) of the serofast patients progressed to neurosyphilis and cardiovascular syphilis. Conclusion These findings demonstrate that most serofast patients with positive nontreponemal IgM antibodies have evidence of progressive syphilis, and nontreponemal IgM antibodies can be used as a new serologic marker for the activity of syphilis. Nontreponemal IgM antibodies may play a role in the management of serofast patients.