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IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 μg/m

Recently, ferroptosis has been reported to be closely related to preeclampsia (PE). However, the mechanisms associated with ferroptosis in PE have been poorly studied.A PE rat model was established via reduced uterine perfusion pressure (RUPP) surgery. A Ferroptosis inhibitor was used to treat the model rats. Blood pressure, urine protein, sFlt-1, GSH, GSH-PX, MDA, total Fe, Fe (II), and Fe (Ⅲ) levels were detected. Placenta morphological changes and fetal survival rate were observed and counted, respectively. miRNA sequencing and bioinformatical analysis were conducted to establish the ferroptosis-related interaction network of miRNAs-mRNAs in PE. After hypoxia treatment, cells were silenced glutamic-oxaloacetic transaminase1 (GOT1) or overexpressed miR-2115-3p/GOT1. Cellular proliferation, invasion, and reactive oxygen species (ROS) were determined. The ferroptosis-related factors levels (ACSL4, TfR1, GPX4, SCL7A11, GSH, GSH-PX, Fe (II), and MDA) were quantified.In vivo, ferrostatin-1 attenuated ferroptosis in the PE models, significantly increasing fetal survivability. The miR-2115-3p/GOT1 pathway was screened for possible association with abnormal ferroptosis in PE. miR-2115-3p was discovered to interact with the mRNA of GOT1. Inhibition of GOT1 and overexpression of miR-2115-3p reversed the decrease in cell proliferation capacity, GSH, GSH-PX, and GPX4 levels, and the increase in ROS, ACSL4, TfR1, MDA, total Fe, and Fe (II) levels induced by hypoxia. However, simultaneous overexpression of miR-2115-3p and GOT1 reversed the above results of overexpression of miR-2115-3p.miR-2115-3p might interact with the GOT1 mRNA to downregulate its expression, further inhibiting the hypoxia-promoted ferroptosis in a PE model.

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy.Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists.The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P 0.0001).ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic nonsquamous non-small-cell lung cancer (AMnsqNSCLC). The study met the primary endpoint of PFS as of 15November2019. Here we report final survival analysis from ORIENT-11 (NCT03607539) using a 15September2021 data cutoff.Patients with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR or ALK genomic tumor aberrations were randomly assigned to sintilimab + pemetrexed-platinum (n = 266) or placebo + pemetrexed-platinum (n = 131). Patients were stratified by PD-L1 expression, platinum-chemotherapy, and gender. Treatment continued until PD, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo + pemetrexed-platinum arm could be sequenced to second-line sintilimab monotherapy, contingent upon PD. Response was assessed (RECISTv.1.1) by blinded independent radiographic review committee. Primary endpoint was PFS. OS was a secondary endpoint and defined from date of randomization to date of death due to any cause. Final OS analysis was defined as approximately 2 years after last patient randomized or when approximately 65 % of patients died, whichever first.At data cutoff of final OS analysis, median study follow-up was 30.8 months. Of 397 patients, 243 OS events were observed (sintilimab + pemetrexed-platinum:151[57 %];placebo + pemetrexed-platinum:92 [70 %]). Of the patients in placebo + pemetrexed-platinum arm, 47 % crossed over to sintilimab monotherapy per protocol. Median OS was 24.2 months in sintilimab + pemetrexed-platinum arm and 16.8 months in placebo + pemetrexed-platinum arm (HR:0.65[95 % CI:0.50,0.85]). Estimated 2-year OS rates were 50 %(sintilimab + pemetrexed-platinum) and 32 %(placebo + pemetrexed-platinum). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95 % CI:0.38,0.69). OS benefit across all prespecified subgroups was largely consistent with that observed in the ITT population.In the ORIENT-11 final OS analysis, sintilimab + pemetrexed-platinum demonstrated improved OS compared to placebo + pemetrexed-platinum when administered as first-line therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.

Background Current polymyxin B dosing in children relies on scant data. Objectives To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages. Methods A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33–2.53 mg/kg/day), and the median age was 12.5 (range 3.2–17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed. Results PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50–100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5–3.0 mg/kg/day had a probability of target attainments over 90% when MICs were Conclusions Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are

In epigenetic research, the abnormality of protein methylation modification is closely related to the occurrence and development of tumors, which stimulates the interest of researchers in protein methyltransferase research and the efforts to develop corresponding specific small molecule inhibitors. Currently, the protein lysine methyltransferase SMYD2 has been identified as a promising new small molecule target for cancer therapy. But its biological functions have not been fully studied and relatively few inhibitors have been reported, thus this field needs to be further explored. This perspective provides a comprehensive and systematic review of the available resources in this field, including its research status, biological structure, related substrates and methylation mechanisms, and research status of inhibitors. In addition, this perspective elaborates in detail the current challenges in this field, our insights into what needs to be done next, rational drug design of novel SMYD2 inhibitors, and foreseeable development directions in the future.

Purpose of Review This review aims to emphasize interesting and important new findings with a focus on the spectrum of spondyloarthritis (SpA) in China. Recent Findings Over the past decade, significant advances have been made in the investigation of SpA epidemiology, the exploration of genetic and environmental risk factors, the identification of clinical features, and the updating of treatment protocols in the Chinese population. The prevalence of ankylosing spondylitis (AS) in China is 0.20–0.42%, and the prevalence of HLA-B27 in AS patients is 88.8–89.4%. HLA-B*2704 is the most common subtype in Chinese AS patients, followed by HLA-B*2705. HLA-A*01, more precisely HLA-A*01:01, may be associated with psoriatic arthritis (PsA). Tumor necrosis factor inhibitors and IL-17A inhibitors have been shown to be effective and safe for AS patients in China. Juvenile-onset AS is relatively rare, accounting for only 9.1% of the AS population. The prevalence of arthritis related to inflammatory bowel disease is 6.9 to 7.2%. A Chinese study showed that the most frequently prescribed medication was methotrexate (66.4%). Biological agents were prescribed in only16.4% of patients with PsA. Summary This review summarizes the latest research in the epidemiology, pathogenesis, clinical manifestations, and management of SpA among Chinese populations. Multiple HLA associations with SpA have also been described, and it is hoped that discoveries of such ethnic-specific risk factor(s) and understanding of their pathological mechanisms may potentially lead to newer targeted therapies for the Chinese populations worldwide.

It is currently accepted that inflammation plays an important role in the pathogenesis of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). However, the efficacy of immunosuppressive therapy remains anecdotal. The objective of this systematic review was to evaluate the efficacy of immunosuppressive therapy in patients with CTD-PAH and to further assess whether response differs between CTD subtypes and clinical features.We systematically searched studies reporting the treatment response of immunosuppressants and biological agents in CTD-PAH from PUBMED, EMBASE, the Cochrane Library, and Scopus. Studies had to report treatment regime and response criteria. The risk of bias was assessed using the Newcastle-Ottawa scale.Seven independent cohorts, 1 trial, and 1 case-series encompassing 439 patients with CTD-PAH were included. Patients were divided into 2 groups according to the therapeutic regimen. There were 146 patients in the immunosuppressants group with better heart function at baseline and 52.1% (76/146) of them were responders. There were 236 patients treated with immunosuppressants combined with PAH-specific therapy who showed more severity at baseline and 41.1% (97/236) of them were responders. Among different CTD subtypes, patients with systemic lupus erythematosus-associated PAH (SLE-PAH) showed a better response to immunosuppressants (response rate 48.1%). What is more, 1 randomized controlled trial showed the potential therapeutic value of rituximab (n = 57) in CTD-PAH patients.Current studies support the use of immunosuppressive therapy in CTD-PAH, especially in SLE-PAH. Further studies on biological agents and the therapeutic effect of different immunosuppressants are still needed.

Background: Rhabdomyolysis (RM) associated acute kidney injury (AKI) is the most common systemic complication of RM. The present study aimed to assess the clinical characteristics and risk factors for intensive care unit (ICU) transfer for patients with RM-associated AKI.Methods: We included all patients who were age ≥ 18 years old with a diagnosis of RM from September 2012 to October 2018 and divided them into RM-associated AKI group and RM without AKI group. The primary outcome was transferring to ICU treatment. Regression analysis was performed to identify factors associated with ICU treatment and recovery of renal function.Results: Among the 149 patients with RM, 68 (45.6%) developed AKI. The percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% versus 12.3%, P < 0.002). Additionally, patients with AKI had higher percentage of undergoing dialysis (19.1% versus 2.5%, P < 0.01), all-cause mortality (13.2% versus 1.2%, P < 0.01), cost of hospitalization [10.8 1,000 yuan, IQR (5.5, 3.5) versus 5.9 1,000 yuan, IQR 5.9 (3.6, 9.9), P = 0.03], as well as longer length of hospital stay [8.0 (5.0, 14.0)] versus [6.0 (4.0, 11.0)], P = 0.02). Moreover, most patients with AKI achieved complete recovery (77.9%) at discharge. After adjusting for potential risk factors, RM-associated AKI remained an independent risk factor for ICU transfer (OR = 3.0, 95% CI, 1.11–8.3, P = 0.03). However, ICU transfer was not associated with recovery of renal function (OR = 0.88, 95% CI, 0.22–3.57, P = 0.856).Conclusion: RM leaded to AKI in most patients. RM-associated AKI could cause worse clinical outcome and predict ICU transfer for patients with RM.

BACKGROUND: Nasopharyngeal carcinoma (NPC), the common malignant head and neck cancer, is highly prevalent in southern China. The molecular mechanism underlying NPC tumorigenesis is unclear. We used 5-Aza-CdR, a DNA methyltransferase inhibitor, to treat NPC cell lines and discovered that the expression of TMEM130 changed significantly compared with the untreatment cells. This study aimed to identify the relationship between the DNA methylation status of TMEM130 and NPC, and to explore the function of TMEM130 in NPC cell migration. METHODS: qRT-PCR was performed to investigate the transcriptional expression of TMEM130 in NPC. Bisulfite sequencing PCR and 5-Aza-CdR treatment were used to detect the methylation level of the TMEM130 promoter. Gene Expression Omnibus (GEO) datasets were obtained to identifiy the methylation status and mRNA expression of TMEM130 in NPC and normal control tissues. Transwell and western blot analyses were used to detect cell migration ability after transfection of TMEM130/NC plasmids in NPC cells. RESULTS: The transcriptional expression of TMEM130 was decreased in NPC cell lines compared with in the NP69 cell line. TMEM130 promoter was significantly hyper methylated in three NPC cell lines (C666, CNE, and HONE) but hypo methylated in NP69 cells. The methylation level was higher in NPC than normal control tissues. Additionally, treatment of NPC cells with 5-Aza-CdR increased the TMEM130 mRNA expression level. Overexpression of TMEM130 in NPC cell lines suppressed cell migration ability and affected some epithelial-mesenchymal transition-associated gene expression. CONCLUSIONS: This study is the first to investigate the expression and function of TMEM130 in NPC. It was found that TMEM130 hyper methylation might contribute to NPC migration and this gene might act as a tumor suppressor gene. TMEM130 is a promising biomarker for NPC diagnosis.

Colorectal cancer (CRC) is an extremely malignant tumor with a high mortality rate. Little is known about the mechanism by which forkhead Box q1 (FOXQ1) causes CRC invasion and metastasis through the epidermal growth factor receptor (EGFR) pathway.To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor (HB-EGF)/EGFR pathway.We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis (GEPIA) website (http://gepia.cancer-pku.cn/index.html). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues, and we constructed a stable low-expressing FOXQ1 cell line and verified it with the above method. The expression changes of membrane-bound HB-EGF (proHB-EGF) and soluble HB-EGF (sHB-EGF) in the low-expressing FOXQ1 cell line were detected by flow cytometry and ELISA. Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells. Proliferation experiments, transwell migration experiments, and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF, and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate. PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways. Knockdown of FOXQ1 suppressed the expression of HB-EGF, and led to a decrease in EGFR and its downstream genesBased on these collective data, we propose that FOXQ1 promotes the invasion and metastasis of CRC

To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19).This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate.A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P0.01). No serious adverse events occurred during treatment.BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.

Compared with traditional computed tomography (CT), dual-layer spectral detector CT (SDCT) shows significant improvement in imaging soft tissues of the digestive tract. This work aimed to explore the application of SDCT to evaluate the expression of the molecular marker Ki-67 in colorectal cancer.We retrospectively analyzed the imaging data of the SDCT (IQon Spectral CT; Philips Healthcare) of 45 patients with colorectal cancer in our centre. We used Spearman's test for the imaging parameters (reconstruction of 40, 70, and 100 keV virtual monoenergetic images [VMIs] and the slope of the Hounsfield unit attenuation plot [VMI Slope] based on venous phase CT images, the arterial phase iodine concentration [AP-IC] and venous phase iodine concentration [VP-IC], and the effective atomic number [Z effect]) and correlation analysis for the Ki-67 index. Multivariate logistic regression was used to eliminate confounding factors. We evaluated the expression level of Ki-67 and drew the receiver operating characteristic curve.The 40-keV VMI, VMI Slope, and AP-IC were found to better reflect the Ki-67 index in patients with colorectal cancer with statistical significance. The 40-keV VMI (r = -0.612, p0.001) and VMI Slope (r = -0.523, p0.001) were negatively correlated with the Ki-67 index, and AP-IC (r = 0.378, p = 0.010) was positively correlated with the Ki-67 index. The other indexes (p0.05) were not statistically significant. The SDCT parameters demonstrated good performance, with area under curves of 0.785 for 40-keV VMI and 0.752 for AP-IC.The SDCT parameters 40-keV VMI and AP-IC can be used for preliminary evaluation of the Ki-67 index in colorectal cancer.

Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic leukoencephalopathy caused by duplication of the lamin B1 gene (LMNB1) or LMNB1 upstream deletions. Neuronal intranuclear inclusion disease (NIID) is another leukoencephalopathy due to GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene. Here, we report two Chinese ADLD families with neuroimaging and clinical features mimicking NIID.We conducted detailed medical history inquiry, neurological examinations, and magnetic resonance imaging in the two families. Candidate gene sequencing and whole exome sequencing (WES) with copy number variation analysis were used to screen the genetic variations. The special points on the clinical and neuroimaging findings in the current families and differential diagnosis of ADLD with NIID are discussed.The two families presented with slowly progressive, multiple central nervous system symptoms, including spastic paraplegia, autonomic dysfunction, ataxia, deep sensory loss, and tremor. Clinical phenotypes were consistent within the family. Transient hypoglycemia and transient dilated pupils indicating autonomic dysfunctions were recorded for the first time in ADLD. Brain MRI showed band-like hyperintensities at the cortico-medullary junction on DWI, typical for NIID. Skin biopsy and genetic sequencing of the NOTCH2NCL gene did not support the diagnosis of NIID. Further whole exome sequencing (WES) identified the duplication mutation spanning the entire LMNB1 gene.The novel feature of transient hypoglycemia and dilated pupils broadens the spectrum of autonomic dysfunction in ADLD. Clinical manifestations and neuroimaging of ADLD can mimic NIID. Although ADLD is even rarer than NIID, the differential diagnosis of these two diseases should not be confused.

Frequent relapse is a prominent challenge in managing immunoglobulin G4-related disease (IgG4-RD). According to the types of organs involved in relapse, relapse patterns were divided into recurrent organ involvement (ROI) and new organ involvement (NOI). We aimed to investigate the discrepancy in clinical relapse patterns and establish an effective prognostic nomogram for NOI.We retrospectively enrolled 125 IgG4-RD patients who experienced relapse during the follow-up period. Patients were classified into two groups: those with NOI (including NOI and NOI + ROI) and without NOI (ROI). Logistic regression analyses were used to assess the risk factors for NOI. The results were externally validated by a separate prospective cohort of 39 patients with relapse.There were 81 (64.8%) and 44 (35.2%) patients without NOI and with NOI, respectively. Patients without NOI showed higher baseline disease activity. The most common ROIs were the lacrimal gland and submandibular gland, while the lung and urinary system were the most involved in NOI. Re-elevation of serum IgG4 level to 74.31% of baseline was associated with NOI. Multiple relapses, organ involvement type at baseline, glucocorticoids combined with immunosuppressive drugs (IM) or IM alone during the maintenance period, and relapse IgG4/baseline IgG4 ratio were included in the nomogram. Both internal and external validations showed good agreement and discrimination.About one third of IgG4-RD patients with relapse suffer from NOI. We developed a risk stratification model that can effectively predict the future risk of NOI. Glucocorticoid and IM combined therapy during maintenance is also recommended.

Pain is a common symptom of an illness. For decades, pain treatments such as non-steroidal anti-inflammatory drugs, opioids, and surgical nerve blocking have been widely used, but each method has its limitations. Photobiomodulation is a recently developed method for pain management, with light-emitting diodes (LEDs) being a more recent development used in pain management because of their low cost, low side effects, and high safety. Here, we reviewed the phototherapeutic effects of LEDs on different pain conditions. We also discussed possible physicochemical and neurobiological mechanisms underlying LED therapy, especially its effects on inflammatory pain.

Camrelizumab is a recently developed PD-1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma.Of 51 advanced lung adenocarcinoma patients with negative driver genes who received camrelizumab plus CP chemotherapy were recruited. These patients received four cycles of camrelizumab plus CP chemotherapy in a 21-day cycle. Then, camrelizumab, pemetrexed or camrelizumab plus pemetrexed was administered as maintenance therapy.The rates of complete response, partial response, stable disease and progressive disease were 2.0%, 56.8%, 19.6% and 5.9%, respectively; while treatment response of 15.7% of patients was missing or not evaluable. The objective response and disease control rates were 58.8% and 78.4%, respectively. With a median follow-up period of 14.9 months (the follow-up duration ranged from 3.9 months to 24.3 months), 41 (83.4%) cases of disease progression and 22 (43.1%) cases of death were recorded. The median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI): 8.4-12.6 months) with a 1-year PFS rate of 36.3% and a 2-year PFS rate of 7.5%. In addition, the median overall survival (OS) was 18.7 months (95% CI: 16.4-21.0 months) with a 1-year OS rate of 79.1% and a 2-year OS rate of 30.4%. In consideration of safety, the most frequent adverse events were peripheral neuropathy (37.3%), neutropenia (37.3%), alopecia (35.3%), etc. and most of them were grade 1-2 and could be controlled.Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients.

ObjectiveFetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes.DesignWe profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up.ResultsAdverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances ofEnterococcusandAcinetobacterand downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants.ConclusionDysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

Functional traits of seeds reflect plant reproductive strategies adapting to environmental changes, which is an evolutionary behavior in natural selection and genetics. Study on seed functional traits is of great significance to deeply understand the long-term adaptive evolution of plants and seeds. We measured seed functional traits of a main indigenous species种子功能性状反映了植物适应环境变化的繁殖对策,这是植物在自然环境选择和遗传上的一种进化行为,对深入认识植物及种子对环境的长期适应性进化意义重大。本研究对中国滨海6个省市9个地区的滨海沼泽湿地(21°29′—40°57′ N)主要土著植物芦苇种子功能性状(包括种子大小、重量、结实率和产量)进行研究,分析其纬度变异规律。结果表明: 我国滨海湿地芦苇种子各功能性状在不同纬度差异显著,各功能性状间具有显著的相关性。芦苇种子大小(种长、种宽、种形指数、长宽比、种子表面积)和百粒重与纬度呈显著的二次函数关系,随着纬度升高先降后升,而种子结实率呈现先升后降的规律,芦苇种子数量与大小间存在着权衡关系。单位面积种子产量随着纬度升高显著增加。逐步回归分析显示,气候因素是影响不同纬度间芦苇种子功能性状差异的主要因素,土壤孔隙水的pH和盐度次之。.

The novel coronavirus disease 2019 continues to spread widely, not only causing physical disorders in patients but also impairing mental health, bringing a heavy burden on global public health. This study aimed to evaluate the anxiety and depression status of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant in Shanghai.This study aimed to retrospectively analyze 2000 patients infected with the SARS-CoV-2 Omicron variant. Data from patients assessed with demographic information, anxiety and depressive symptoms were collected using a questionnaire. Clinical and laboratory data were collected using electronic medical system. Anxiety and depression were assessed using the Self-Rating Anxiety Scale, the Generalized Anxiety Disorder Scale, and the Patient Health Questionnaire. Clinical information and laboratory indicators included age, sex, blood pressure, blood glucose, basic disease, time of diagnosis onset, duration of hospitalization, vaccination status of novel coronavirus disease 2019, and virus-negative conversion time.This study will provide evidence-based suggestions for early psychological intervention in patients infected with the SARS-CoV-2 Omicron Variant.

Introduction: The objective of this study was to investigate changes in serum lipids among HIV-infected patients switching from non-nucleoside-reverse transcriptase inhibitors (NNRTI) to protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), and to determine if changes of lipid profiles impacted the monocyte subsets recovery. Methodology: Fifty-seven subjects who switched from NNRTIs to PI-based HAART (NNRTIs to PI group) and fifty-five subjects who initially started with PI-based HAART (initial PI group) were recruited. According to their baseline triglyceride (TG) levels, the NNRTIs to PI and initial PI groups were further divided into non-hypertriglyceridemia and hypertriglyceridemia subgroups, respectively. The effects of PI-based HAART on lipid profiles and monocyte subsets were analyzed. Results: At 48 weeks, the TG changes in the NNRTIs to PI group was higher than that of the initial PI group. The increases of serum TG levels in the initial PI non-hypertriglyceridemia group was greater than that of the NNRTIs to PI non-hypertriglyceridemia group. For the hypertriglyceridemia group at baseline, significant increment in TG levels were observed in the NNRTIs to PI hypertriglyceridemia group. The percentages of circulating CD14highCD16+ and CD14lowCD16+ subsets were elevated in the two groups. At 48 weeks, the proportion of CD14highCD16+ monocytes declined gradually, and the proportion of CD14lowCD16+ monocytes decreased independently of the TG level. Conclusions: For non-hypertriglyceridemia individuals at baseline, PI-based regimens increased the TG level in the initial PI group. For the NNRTIs to PI hypertriglyceridemia group, PI-based regimens reinforced HAART-related hypertriglyceridemia.

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.

The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free β-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free β-hCG level was significantly lower in the study group. The triple-index model of free β-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free β-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free β- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free β-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free β-hCG, free β-hCG, AFP-L3, AFP + free β-hCG, and AFP. Indicators of maternal serum free β-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free β-hCG demonstrated better screening efficiency.

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-β-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100–40.0 and 0.400–200 μg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.

tRNA is the most extensively modified RNA in cells. On average, a bacterial tRNA contains 8 modifications per molecule and a eukaryotic tRNA contains 13 modifications per molecule. Recent studies reveal that tRNA modifications are highly dynamic and respond extensively to environmental conditions. Functions of tRNA modification dynamics include enhanced, on-demand decoding of specific codons in response genes and regulation of tRNA fragment biogenesis. This review summarizes recent advances in the studies of tRNA modification dynamics in biological processes, tRNA modification erasers, and human-associated bacteria. Furthermore, we use the term "metaepitranscriptomics" to describe the potential and approach of tRNA modification studies in natural biological communities such as microbiomes. tRNA is highly modified in cells, and tRNA modifications respond extensively to environmental conditions to enhance translation of specific genes and produce tRNA fragments on demand. We review recent advances in tRNA sequencing methods, tRNA modification dynamics in biological processes, and tRNA modification studies in natural communities such as the microbiomes.

Although increasing evidence links the gut microbiota with the development of colorectal cancer, the molecular mechanisms for microbiota regulation of tumorigenesis are not fully understood. Here, we found that a member of the TNFα-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) was significantly upregulated in murine intestinal tumors and in human colorectal cancer, and colorectal cancer with high expression of Tipe2 mRNA associated with reduced survival time of patients. Consistent with these findings, TIPE2 deficiency significantly inhibited the development of colorectal cancer in mice treated with azoxymethane/dextran sodium sulfate and in Apcmin/+ mice. TIPE2 deficiency attenuated the severity of colitis by successfully resolving and restricting colonic inflammation and protected colonic myeloid cells from death during colitis. Transplantation of TIPE2-deficient bone marrow into wild-type mice successfully dampened the latter's tumorigenic phenotype, indicating a hematopoietic-specific role for TIPE2. Mechanistically, restricting the expansion of Enterobacteriaceae/Escherichia coli (E. coli) decreased intestinal inflammation and reduced the incidence of colonic tumors. Collectively, these data suggest that hematopoietic TIPE2 regulates intestinal antitumor immunity by regulation of gut microbiota. TIPE2 may represent a new therapeutic target for treating colorectal cancer.

There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC.This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis.Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; PThis non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP).We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3 years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6 months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment.Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6 months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6 months of GC therapy were more likely to relapse in the follow-up of 3 years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6 months.Patients with persistent pancreatic swelling after GC-based therapy of 6 months were more likely to relapse in the follow-up of 3 years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6 months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.

To evaluate the effect of intensive oropharyngeal functional training on swallowing in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.Fourteen patients with nasopharyngeal carcinomas and dysphagia after radiotherapy received intensive oropharyngeal training for two weeks. The Functional Oral Intake Scale (FOIS) and videofluoroscopic swallowing studies (VFSS) were used to evaluate swallowing function before and after intensive oropharyngeal training. Spatiotemporal parameters of the VFSS were analyzed using a digital image analysis system.After training, the FOIS, Rosenbek penetration-aspiration score, DIGEST, normalized residue ratio scale, and spatiotemporal parameters of VFSS were significantly improved (P 0.05).This study indicated that intensive oropharyngeal training improves swallowing function after radiotherapy in patients with nasopharyngeal carcinoma.

The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population.A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR60 mL·min -1 ·1.73 m -2 .After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β -2.53, 95% confidence interval -3.89, -1.17, Ptrend0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no).Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.

More information is needed about the efficacy and safety of compounded bioidentical hormone therapy (cBHT) in the published literature. A thorough synthesis of existing data is not currently available.To provide a systematic review and meta-analysis of the existing evidence related to the safety and efficacy of commonly prescribed cBHT preparations in perimenopausal and postmenopausal women.PubMed, ClinicalTrials.gov, and The Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing cBHT with a placebo or FDA-approved products in perimenopausal or postmenopausal women were eligible. The risk of bias was assessed by the Cochrane risk of bias tool. The primary safety outcome was changes in lipid profile and glucose metabolism, and the primary efficacy outcome was the change of vaginal atrophy symptoms. The secondary outcomes included the change of endometrial thickness, risk of adverse events, vasomotor symptoms, change of serum hormone levels, and change of bone mineral density.A total of 29 RCTs reported in 40 articles containing 1,808 perimenopausal and postmenopausal women were included. Two risk factors of cardiovascular disease, lipid profile, and glucose metabolism, were evaluated with cBHT. The results showed that compounded androgen was not associated with change of lipid profile or glucose metabolism. There was no change in endometrial thickness or serious adverse events. There were more androgenic side effects with compounded dehydroepiandrosterone compared with placebo as expected. Other safety measures including clinical cardiovascular events, endometrial biopsy, and risk of breast cancer were not studied. cBHT in the form of compounded vaginal androgen was found to significantly improve vaginal atrophy symptoms (SMD -0.66 [95% CI, -1.28 to -0.04]; I2 = 86.70%). This finding was supported by the association between compounded vaginal androgen and improved female sexual function scores. The changes of serum hormone levels were also evaluated. Despite the variations in absorption from different types of compounded hormones, routes, and strengths, the trends were consistent with published data from FDA-approved products.This review found that cBHT used in primarily short-term RCTs is not associated with adverse changes in lipid profile or glucose metabolism. cBHT in the form of vaginal androgens appears beneficial for vaginal atrophy symptoms. There are insufficient RCTs of cBHT to assess clinical risk of breast cancer, endometrial cancer, or cardiovascular disease. Long-term studies with clinical endpoints are needed.

Background To compare the results between type I tympanoplasty performed with transcanal endoscopic ear surgery (TEES) and microscopic ear surgery (MES) for treatment of chronic otitis media in a homogenous group of patients. Methods A retrospective study was performed in our department between January 2011 and January 2016 to review primary type I tympanoplasty cases with a subtotal perforation, an intact ossicular chain, a dry ear for at least 1 month, normal middle ear mucosa, and a follow-up period of at least 6 months post surgery. The adoption of TEES or MES was divided temporally (before and since 2013). TEES was undertaken in 224 patients (224 ears) and MES in 121 patients (121 ears). Results The successful graft take rate was 94.64% (212/224) in the TEES group and 90.91% (110/121) in the MES group (P = 0.239). The improvements in the air conduction levels between the 2 groups were not statistically different at 1, 3, or 6 (> 6) months (P > 0.05) after surgery. The improvements in the air–bone gaps were not significantly different between the 2 groups (P > 0.05). The average hearing gains in the TEES group 6 (and > 6) months post surgery were 11.85 ± 5.47 dB, which was better than 10.48 ± 5.18 dB in the MES group (P = 0.031). The use of medical resources was lower in the TEES group than in the MES group regarding the average operating time (49.22 ± 8.24 min vs 81.22 ± 14.73 min, respectively; P P Conclusion TEES for type I tympanoplasty seems to achieve a shorter operative time and ideal tympanic membrane healing rate and hearing results in patients with chronic otitis media.

Diarrhea is the third leading cause of death in developing countries in children under the age of five. About half a million children die of diarrhea every year, most of which in developing countries. Viruses are the main pathogen of diarrhea. In China, the fecal virome of children with diarrhea has been rarely studied. Using an unbiased viral metagenomics approach, we analyzed the fecal virome in children with diarrhea. Many DNA or RNA viruses associated with diarrhea identified in those fecal samples were mainly from six families of Adenoviridae, Astroviridae, Caliciviridae, Parvoviridae, Picornaviridae, and Reoviridae. Among them, the family of Caliciviridae accounts for the largest proportion of 78.42%, following with Adenoviridae (8.94%) and Picornaviridae (8.36%). In addition to those diarrhea-related viruses that have already been confirmed to cause human diarrhea, the viruses not associated with diarrhea were also identified including anellovirus and picobirnavirus. This study increased our understanding of diarrheic children fecal virome and provided valuable information for the prevention and treatment of viral diarrhea in this area.

The rational design and preparation of available fullerene@metal-organic matrix hybrid materials are of profound significance in electrochemical biosensing applications due to their unique photoelectric properties. In this work, C

The pangolin is the only scaly mammal in the world and also an important reservoir of pathogenic viruses. Habitat loss and poaching have been shrinking the survival range of pangolins. More information on pangolin virus populations is needed to better understand and assess potential disease risks. In this study, viral metagenomic data were used to reinvestigate the virome in pangolin lung tissue. Complete genome sequences of two novel anelloviruses were acquired and clustered with the referenced feline strains belonging to genus Tettorquevirus and genus Etatorquevirus, respectively. Two genomes belonging to the genus Gemykibivirus, and species Bat-associated cyclovirus 9 were detected, respectively. One genome with a large contig belonging to the genus Senecavirus were also characterized, according to phylogenetic analysis, which can be presumed to be a novel species. In addition, a full genome of endogenous retroviruse (ERV) was assembled from the lungs of pangolin, and this virus may have the possibility of cross-species transmission during the evolution. This virological investigation has increased our understanding of the virome carried by pangolins and provided a reference baseline for possible zoonotic infectious diseases in the future.

All

Preeclampsia is a complication of pregnancy characterized by high blood pressure and organ damage after 20 gestational weeks. It is associated with high maternal and fetal morbidity and mortality. However, at present, there is no effective prevention or treatment for this condition. Previous studies have revealed that plasma exosomal mirnas from pregnant women with preeclampsia could serve as biomarkers of pathogenic factors. However, the roles of plasma exosomal mirnas in preeclampsia with severe features (sPE), which is associated with poorer pregnancy outcomes, remain unknown. Thus, the aims of this study were to characterize plasma exosomal miRNAs in sPE and explore the related pathogenic mechanisms using bioinformatic analysis. Plasma exosomes were isolated using a mirVana RNA isolation kit. the exosomal miRNAs were detected using high-throughput sequencing and the mirnas related to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) terms were analyzed using the clusterprofiler package of R. Fifteen miRNAs exhibited increased expression and fourteen miRNAs exhibited reduced expression in plasma exosomes from women with sPE as compared to normal pregnant women. Further, gene set enrichment analysis revealed that the differentially expressed plasma exosomal miRNAs were related to the stress response and cell junction regulation, among others. In summary, this study is the first to identify the differentially expressed plasma exosomal miRNAs in sPE. These findings highlight promising pathogenesis mechanisms underlying preeclampsia.

Colorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of minimally invasive and precise biomarkers is an urgent need for the early diagnosis of CRC. Through bioinformatics analysis of 395 CRC tissues and 63 CRC cell lines, CK18, CK20, de-methylated HPDL and hyper-methylated CLIP4 were identified as candidate serum biomarkers. Then, a training cohort consisting of 60 CRC, 30 colorectal adenomas (CA) and 33 healthy controls and a validation cohort consisting of 60 CRC, 30 CA and 30 healthy controls were enrolled. In the training cohort, enzyme-linked immunosorbent assay (ELISA) showed that CK18 and CK20 were all significantly higher in CRC and CA. CK18 diagnosed CRC with 46.67% sensitivity and 87.3% specificity; CK20 diagnosed CRC with 28.33% sensitivity and 90.47% specificity. Methylation-specific PCR (MSP) indicated that de-methylated HPDL and hyper-methylated CLIP4 were significantly detected in CRC and CA. De-methylated HPDL diagnosed CRC with 36.67% sensitivity and 93.65% specificity and hyper-methylated CLIP4 with 73.33% sensitivity and 84.13% specificity. Random combined analysis suggested that CK20/hyper-methylated CLIP4 diagnosed CRC with 91.67% sensitivity and 82.54% specificity. In the validation cohort, CK20 diagnosed CRC with 36.7% sensitivity and 88.3% specificity and hyper-methylated CLIP4 with 80% sensitivity and 85% specificity. CK20/hyper-methylated CLIP4 diagnosed CRC with 95% sensitivity and 81.7% specificity. Compared with serum biomarkers reported before, CK20/hyper-methylated CLIP4 possessed the potential to be a new effective and precise diagnostic biomarker for CRC.

Implantation of intraocular lens after combined procedure of vitrectomy and cataract surgery is usually required to reduce the postoperative refraction errors. However, because of the severe fibrosis of the anterior capsule and the adhesion between the anterior and posterior capsules, it is difficult to reopen the capsular bag to complete the secondary IOL implantation. We describe here a surgical approach for reopening the severe adhesion between capsules and removing the significant fibro-proliferative membranous material by injecting viscoelastic agent into the periphery of the capsular bag to separate the anterior and posterior capsules. The IOL was implanted into the capsular bag without any zonular rupture or posterior capsule tear. The position of the intraocular lens was stable during postoperative follow-ups up to 3 months. Our procedure to open a severely fibrosis capsule is safe and effective, and may be used as a preferred method.

d-2-Hydroxyglutarate (d-2-HG) is a metabolite involved in many physiological metabolic processes. When d-2-HG is aberrantly accumulated due to mutations in isocitrate dehydrogenase or d-2-HG dehydrogenase, it functions in a pro-oncogenic manner and is thus considered a therapeutic target and biomarker in many cancers. In this study, DhdR from Achromobacter denitrificans NBRC 15125 is identified as an allosteric transcriptional factor that negatively regulates d-2-HG dehydrogenase expression and responds to the presence of d-2-HG. Based on the allosteric effect of DhdR, a d-2-HG biosensor is developed by combining DhdR with amplified luminescent proximity homogeneous assay (AlphaScreen) technology. The biosensor is able to detect d-2-HG in serum, urine, and cell culture medium with high specificity and sensitivity. Additionally, this biosensor is used to identify the role of d-2-HG metabolism in lipopolysaccharide biosynthesis of Pseudomonas aeruginosa, demonstrating its broad usages., d-2-hydroxyglutarate (d-2-HG) is a metabolite that can be aberrantly accumulated and acts as a biomarker in many cancers. Here the authors report a d-2-HG biosensor based on the allosteric transcription factor DhdR which they use for detection in serum and urine.

Background There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants (EPIs) and there is no unified recommendation on the active treatment of the minimum gestational age in the field of perinatal medicine in China. We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations. Methods We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age (GA) between 24+0 and 27+6 weeks from 2010 to 2019. Results Of the 1163 EPIs included in our study, 241 (20.7%) survived, while 849 (73.0%) died in the delivery room and 73 (6.3%) died in the neonatal intensive care unit. Among all included EPIs, 862 (74.1%) died from withholding or withdrawal of care. Regardless of stratification according to GA or birth weight, the proportion of total mortality attributable to withdrawal of care is high. For infants with the GA of 24 weeks, active treatment did not extend their survival time (P = 0.224). The survival time without severe morbidity of the active treatment was significantly longer than that of withdrawing care for infants older than 25 weeks (P P Conclusions The mortality rate of EPIs is still high. Withdrawal of care is common for EPIs with smaller GA, especially in the delivery room. It is necessary to use a multi-center, large sample of real-world data to find the survival limit of active treatment based on our treatment capabilities.

We used viral metagenomics and next-generation sequencing to identify a novel strain of bocaparvovirus in the intestinal tract of tufted deer (Elaphodus cephalophus), tentatively named "Elaphodus cephalophus bocaparvovirus" (ECBOV). A nearly complete genome sequence of 5,354 nucleotides was obtained, which had the typical genome organization and protein motifs of a bocaparvovirus. Sequence comparisons and phylogenetic analysis revealed that ECBOV may be a new ungulate bocaparvovirus. The identification and characterization of viruses in wildlife will facilitate our understanding of genetic evolution and cross-species transmission and thus further reduce the potential threat to human and animal health. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05308-3.

Objective Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. Methods In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. Results Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p

OBJECTIVES To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. METHODS A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. RESULTS Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P

There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is a need for novel chemotherapeutic drugs for the efficient treatment of colorectal cancer patients. In the present study, we screened 160 drugs approved by the Food and Drug Administration and identified that cabazitaxel (CBT), a microtube inhibitor, can suppress colony formation and cell migration of colorectal cancer cells in vitro. CBT also induces G2/M phase arrest and apoptosis of colorectal cancer cells. Most importantly, it inhibits the growth of colorectal cancer cell xenograft tumors in vivo. Transcriptome analysis by RNA‐sequencing revealed that Tub family genes are abnormally expressed in CBT‐treated colorectal cancer cells. The expression of several p53 downstream genes that are associated with cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis is induced by CBT in colorectal cancer cells. Overall, our results suggests that CBT suppresses colorectal cancer by upregulating the p53 pathway, and thus CBT may have potential as an alternative chemotherapeutic drug for colorectal cancer., In the present study, we screened 160 drugs approved by the Food and Drug Administration, aiming to identify novel chemotherapeutic agents for colorectal cancer (CRC) treatment. We identified that the microtubule inhibitor cabazitaxel (CBT) has a suppressive effect on CRC cells both in vitro and in vivo. Transcriptome analysis revealed that CBT induced apoptosis in CRC cells by upregulating the p53 pathway, implying that CBT may hold chemotherapeutic potential for the treatment of patients with CRC.

Traditional paper documents with Braille characters and tangible graphics have obvious defects to disseminate knowledge in the information age. Information accessibility is an urgent challenge for blind individuals. Although many types of tactile displays were created for different applications, we especially focus on the tactile display for visually impaired people, which can dynamically generate tangible graphics and Braille characters, to help the blind obtain information conveniently. In this article, we present the state-of-the-art of graphic tactile displays (GTDs) and refreshable Braille displays (RBDs), then discuss their common kernel technologies about actuators and latch structures. This article summarizes the performance of typical actuators of tactile displays and analyzes the working principles of some latch structures. This article systematically summarizes latch structures of GTDs and RBDs, for the first time. Several comments in this paper will be useful to develop high-performance tactile displays for visually impaired people.

To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms.MTT assay and trypan blue dye exclusion method were used to evaluate the effect of atovaquone on the proliferation of Raji cells. After the cells were stained by PI staining, the cell cycle distribution was detected by flow cytometry. Cell apoptosis was analyzed by Annexin V/PI double binding assay. The intracellular alterations of reactive oxygen species were detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expression of cell cycle and apoptosis related molecules were detected by Western blot.Various concentrations of atovaquone (5-40 μmol/L) inhibited the growth of Raji cells in a concentration-dependent manner (Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.阿托伐醌诱导非霍奇金淋巴瘤Raji细胞周期阻滞和细胞凋亡.探讨阿托伐醌对非霍奇金淋巴瘤Raji细胞周期与细胞凋亡的影响与作用机制。.分别采用MTT比色法和锥虫蓝染色法检测阿托伐醌对Raji细胞增殖的作用；PI染色后采用流式细胞术检测细胞周期分布；Annexin V/PI双染法检测细胞凋亡；DCFH-DA探针标记检测细胞内活性氧水平变化；Western blot法检测细胞周期和凋亡相关分子的蛋白表达。.不同浓度阿托伐醌（5-40 μmol/L）剂量依赖性抑制Raji细胞增殖（阿托伐醌有效抑制Raji细胞增殖，并可能通过抑制STAT3信号通路诱导细胞周期G

To observe the clinical efficacy of "Tong Guan Li Qiao"(unblocking gates and orifices) needling method combined with swallowing training in the treatment of post-stroke dysphagia (PSD) and its effect on surface electromyography (sEMG) and cerebral microcirculation.A total of 116 patients with PSD were randomly divided into observation group (The total effective rate of the observation group was 94.92% (56/59), higher than 82.46% (47/57) of the control group("Tong Guan Li Qiao" needling method combined with swallowing training can effectively improve cerebral microcirculation, enhance the motor function of swallowing muscles and promote the recovery of swallowing function in treating PSD patients.