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Abstract Intracranial aneurysm is the primary cause of nontraumatic subarachnoid hemorrhage. To assess aneurysm metabolism, we present a method of intra-operatively collecting blood samples from the aneurysm neck, as well as the proximal and distal responsible vessels, using microcatheters. Through these paired comparisons, we can eliminate the interpatient variation usually observed in plasma samples taken from the peripheral vein. We utilized 39 plasma samples from 13 intracranial patients to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry. Our findings revealed that l-tyrosine is upregulated at relatively high levels at the aneurysm neck than the proximal and distal aneurysm, whereas phenylpyruvic acid, l-cystine, and l-ornithine are downregulated. Based on this, there was also a significant decrease in arginine within small aneurysm of the internal carotid artery. The 6-month follow-up indicated that patients who experienced good recovery had lower levels of biliverdin, bilirubin, and metabolites of coenzyme Q within the aneurysm. In conclusion, our investigation provides a comprehensive overview of plasma metabolites in patients with intracranial aneurysms, shedding light on potential pathogenetic mechanisms in unruptured intracranial aneurysms. Moreover, the study proposes innovative ideas for establishing postoperative follow-up timelines for flow diverter devices.

Abstract Background Microsatellite instability-high (MSI-H) tumors, with elevated tumor mutational burden and expression of neoantigens, represent a distinct immune-activated subpopulation in colorectal cancer (CRC), characterized by strong lymph node reaction, locally advanced tumor and higher total lymph nodes harvested (TLN), but less metastatic lymph nodes and fewer incidence of III-IV stage. Host immune response to tumor and lymph nodes may be an important prognostic factor. However, N stage and LNR (Lymph-Node Ratio) have limitations in predicting the prognosis of MSI-H patients. Negative lymph node count (NLC) provided a more precise representation of immune activation status and extent of tumor metastasis. The study aims to detect prognostic significance of NLC in MSI-H CRC patients, and compare it with N stage, TLN and LNR. Methods Retrospective data of 190 consecutive MSI-H CRC patients who received curative resection were collected. Survival analyses were performed using the Kaplan–Meier method. Clinicopathological variables including NLC, N stage, TLN and LNR were studied in univariate and multivariate COX regression analyses. ROC (receiver operating characteristic curve) and concordance index were employed to compare the differences in predictive efficacy between NLC, N stage, TLN and LNR. Results Patients with increased NLC experienced a significantly improved 5-years DFS and OS in Kaplan–Meier analysis, univariate analysis, and multivariate analysis, independent of potential confounders examined. Increased NLC corresponded to elevated 5-years DFS rate and 5-years OS rate. AUC (area under curve) and concordance index of NLC in DFS and OS predicting were both significantly higher than N stage, TLN and LNR. Conclusions Negative lymph node is an important independent prognostic factor for MSI-H patients. Reduced NLC is associated with tumor recurrence and poor survival, which is a stronger prognostic factor than N stage, TLN and LNR.

Abstract Early assessment and accurate staging of liver fibrosis may be of great help for clinical diagnosis and treatment in patients with chronic hepatitis B (CHB). We aimed to identify serum markers and construct a machine learning (ML) model to reliably predict the stage of fibrosis in CHB patients. The clinical data of 618 CHB patients between February 2017 and September 2021 from Zhejiang Provincial People's Hospital were retrospectively analyzed, and these data as a training cohort to build the model. Six ML models were constructed based on logistic regression, support vector machine, Bayes, K-nearest neighbor, decision tree (DT) and random forest by using the maximum relevance minimum redundancy (mRMR) and gradient boosting decision tree (GBDT) dimensionality reduction selected features on the training cohort. Then, the resampling method was used to select the optimal ML model. In addition, a total of 571 patients from another hospital were used as an external validation cohort to verify the performance of the model. The DT model constructed based on five serological biomarkers included HBV-DNA, platelet, thrombin time, international normalized ratio and albumin, with the area under curve (AUC) values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the training cohort were 0.898, 0.891, 0.907 and 0.944, respectively. The AUC values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the external validation cohort were 0.906, 0.876, 0.931 and 0.933, respectively. The simulated risk classification based on the cutoff value showed that the classification performance of the DT model in distinguishing hepatic fibrosis stages can be accurately matched with pathological diagnosis results. ML model of five serum markers allows for accurate diagnosis of hepatic fibrosis stages, and beneficial for the clinical monitoring and treatment of CHB patients.

Abstract Background Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a “bridge-layered” decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. Methods A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point “bridge” decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the “layered” decompression technique. Results Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. Conclusion The “bridge-layered” decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

AbstractMicromelalopha sieversi (Staudinger, 1892) is a significant pest of Poplar trees in China. In this study, we used high-throughput sequencing to sequence the whole mitochondrial genome of M. sieversi. The length of the genome was 15,373 base pairs. The nucleotide composition was 39.8%, 11.5%, 8.0%, and 40.7% for A, C, G, and T, respectively. We used the maximum-likelihood method to construct a molecular phylogenetic tree based on complete mitogenome sequences of 19 Noctuoidea species as ingroups and five Geometroidea species as outgroups. The results indicate that the genus Micromelalopha is closely related to the genus Clostera in family Notodontidae.

Background: Trigeminal neuralgia (TN) secondary to a dural arteriovenous fistula (DAVF) is quite rare, and the goal of treatment is to resolve both the fistula and the pain. Case presentation: We herein report a case of TN secondary to a DAVF in a 64-year-old woman with a 1-year history of right-sided TN. Brain magnetic resonance imaging and digital subtraction angiography showed a right tentorial DAVF. Interventional embolization was performed, but the pain was not relieved after the operation. Six months later, we performed microvascular decompression of the trigeminal nerve. During the operation, we electrocoagulated the tortuous and dilated malformed vein, which was compressing the trigeminal nerve, to reduce its diameter and mitigate the compression on the cisternal segment of the trigeminal nerve. That patient's pain was relieved postoperatively. In addition, we reviewed the literature of TN caused by DAVF and found a total of 30 cases, 22 of which were treated by interventional embolization. Of these 22 cases, the interventional embolization healed the fistula with pain relief in 14 cases and healed the fistula without pain relief in 8 cases. We found that the venous drainage methods of the 8 cases were all classified into the posterior mesencephalic group. Conclusions: We believe that this drainage pattern contributes to the more common occurrence of unrelieved pain. For such patients, microvascular decompression can be performed with intraoperative coagulation to narrow the dilated veins until the cisternal segment of the trigeminal nerve is no longer compressed. Satisfactory curative effects can be obtained using this technique.

Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio (LR) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants (φ) and the percentage of normal cells (Mxn) as a priori parameters when performing calculations. The relationship between LR values and φ or Mxn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log10(LR) values greater than 1014. In the non-contributor test, 99.9% of the quartiles had Log10(LR) values less than 0. When the defense’s hypothesis took into account the possibility that the tumor samples came from the patient’s relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing Mxn. Finally, LR interval value was provided for each tumor sample by considering the confidence interval of Mxn. The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification.

AbstractWe performed the first sequencing of the complete mitogenome of Botyodes diniasalis by high-throughput sequencing. A circular DNA molecule of 15,219 bp in size, encoding 2 rRNAs, 22 tRNAs, and 13 PCGs, contains a non-coding AT-rich region. The overall nucleotide composition of the genome is A (39.5%), T (41.3%), C (11.3%), and G (7.8%). Phylogenetic analysis based on mitogenomic data suggest that the species B. diniasalis has a close evolutionary relationship with B. principalis in Margaroniini. The complete mitogenome of B. diniasalis will serve as a valuable resource for future studies on evolution, taxonomy, genetic conservation, and utilization of Botyodes.

Abstract The C−N axially chiral N-arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well as in chiral ligands/catalysts. Asymmetric synthesis of N-arylpyrroles, however, is still challenging, and the simultaneous creation of contiguous C−N axial and central chirality remains unknown. Herein, a diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. The key transformation is a one-pot, three-component oxo-diarylation reaction, which simultaneously creates a C−N axial chirality and a central quaternary stereogenic center. A broad range of unactivated alkynes were readily employed as a reaction partner in this transformation, and the N-arylpyrrole products are obtained in good yields, with excellent enantioselectivities and very good diastereoselectivities. Notably, the N-arylpyrrole skeletons represent interesting structural motifs that could be used as chiral ligands and catalysts in asymmetric catalysis.

Excessive emissions of heavy metals not only cause environmental pollution but also pose a direct threat to human health. Therefore, rapid and accurate detection of heavy metals in the environment is of great significance. Herein, we propose a method based on laser-induced breakdown spectroscopy (LIBS) combined with filter paper modified with bovine serum albumin-protected gold nanoclusters (LIBS-FP-AuNCs) for the rapid and sensitive detection of Cr3+ and Mn2+. The filter paper modified with AuNCs was used to selectively enrich Cr3+ and Mn2+. Combined with the multi-element detection capability of LIBS, this method achieved the simultaneous rapid detection of Cr3+ and Mn2+. Both elements showed linear ranges for concentrations of 10–1000 μg L−1, with limits of detection of 7.5 and 9.0 μg L−1 for Cr3+ and Mn2+, respectively. This method was successfully applied to the determination of Cr3+ and Mn2+ in real water samples, with satisfactory recoveries ranging from 94.6% to 105.1%. This method has potential application in the analysis of heavy metal pollution.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.

Abstract Bloodstream infections are serious and complex infectious diseases that often require a rapid diagnosis. Polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR‐QDFA) is a novel diagnostic technique. This study aimed to evaluate the diagnostic performance of PCR‐QDFA for pathogen detection in patients with suspected bloodstream infections (BSIs). It evaluates 29 kinds of common pathogens (24 bacteria and 5 yeasts) from blood culture bottles. The results of PCR‐QDFA identification and traditional microbial laboratory identification were compared, and the latter was used as the ‘gold standard’ to analyse the diagnostic performance of the PCR‐QDFA. In total, 517 blood culture bottles were included in this study. The PCR‐QDFA identified microorganisms in 368/422 (87.2%) samples with monomicrobial growth. For the pathogens on the PCR‐QDFA list, the assay showed a higher sensitivity of 97.4% (368/378). When polymicrobial growth was analysed, the PCR‐QDFA successfully detected 19/25 (76%) microorganisms on the PCR‐QDFA list. In addition, 82/82 negative blood culture bottles also showed no pathogens by PCR‐QDFA with a specificity of 100%. In conclusion, the PCR‐QDFA assay could identify a majority of the common pathogens encountered in clinical practice, showing excellent diagnostic performance for pathogen detection in patients with suspected BSIs.

BackgroundFrequent air pollution events in Northwest China pose a serious threat to human health. However, there is a lack of specific differences assessment in PM2.5-related disease burden. Therefore, we aimed to estimate the PM2.5-related premature deaths and health economic losses in this typical northwest region, taking into account disease-specific, age-specific, and region-specific factors.MethodsWe utilized the WRF-Chem model to simulate and analyze the characteristics and exposure levels of PM2.5 pollution in Gansu Province, a typical region of Northwest China. Subsequently, we estimated the premature mortality and health economic losses associated with PM2.5 by combining the Global Exposure Mortality Model (GEMM) and the Value of a Statistical Life (VSL).ResultsThe results suggested that the PM2.5 concentrations in Gansu Province in 2019 varied spatially, with a decrease from north to south. The number of non-accidental deaths attributable to PM2.5 pollution was estimated to be 14,224 (95% CI: 11,716–16,689), accounting for 8.6% of the total number of deaths. The PM2.5-related health economic loss amounted to 28.66 (95% CI: 23.61–33.63) billion yuan, equivalent to 3.3% of the regional gross domestic product (GDP) in 2019. Ischemic heart disease (IHD) and stroke were the leading causes of PM2.5-attributed deaths, contributing to 50.6% of the total. Older adult individuals aged 60 and above accounted for over 80% of all age-related disease deaths. Lanzhou had a higher number of attributable deaths and health economic losses compared to other regions. Although the number of PM2.5-attributed deaths was lower in the Hexi Corridor region, the per capita health economic loss was higher.ConclusionGansu Province exhibits distinct regional characteristics in terms of PM2.5 pollution as well as disease- and age-specific health burdens. This highlights the significance of implementing tailored measures that are specific to local conditions to mitigate the health risks and economic ramifications associated with PM2.5 pollution.

Abstract Objective Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. Methods A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. Results A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. Conclusion Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.

BackgroundGlobally, type 2 diabetes mellitus (T2DM) accounts for approximately 90% of diabetes cases. Resistance training (RT) is frequently employed to diminish Glycated Hemoglobin (HbA1c) and Fast Blood Glucose (FBG) levels in T2DM patients. Yet, the specific dose-response relationships between RT variables such as training duration, frequency, and intensity for T2DM remain under-researched.ObjectivesThis meta-analysis aimed to elucidate the overarching effects of RT on HbA1c and FBG metrics and to provide dose-response relationships of RT variables. This was achieved by examining randomized controlled trials (RCTs) that reported reductions in HbA1c and FBG among T2DM patients.MethodsComprehensive literature searches were conducted up to 25th February 2023 across databases including EMBASE, Pubmed, Cochrane, CENTRAL, Web of Science, CNKI, Wanfang Data, VIP Database for Chinese Technical Periodicals, and the Chinese Biomedical Database. The Physical Therapy Evidence Database (PEDro) was leveraged to appraise the quality of selected studies based on predefined inclusion and exclusion criteria. The meta-analysis was conducted using Stata 16.Results26 studies that include 1336 participants met the criteria for inclusion. RT significantly reduced HbA1c and FBG levels in comparison to control groups (P

BackgroundMicrosatellite stable (MSS) colorectal cancer (CRC) has been referred to as the “cold tumor” because of almost no response to anti–programmed death-1 (PD-1) antibody. A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). However, only a small subset of patients may benefit from the combination therapy. We aim to evaluate the efficacy and safety data of immune checkpoint inhibitors combined with regorafenib in refractory MSS mCRC and to discover biomarkers that can effectively stratify the beneficial patient population.MethodsWe retrospectively analyzed patients with MSS mCRC who received regorafenib combined with anti–PD-1 antibody therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and status of gene mutation were reviewed and evaluated.ResultsTwenty-one patients received combination treatment. At a median treatment duration of 4 months, one patient achieved complete response, three patients achieved partial response, and two patients achieved stable disease as the best response. The ORR and DCR were 19% and 28.5% in the overall population, respectively. The median PFS was 4 months, and the median OS was 25 months. Only erbb2 receptor tyrosine kinase 2/erbb3 receptor tyrosine kinase 3 (ERBB2/ERBB3) mutation status was confirmed to be a potential predictive factor for effective treatment. In patients with ERBB2/ERBB3 mutation, ORR, DCR, and PFS exhibited significant improvements in comparison with that in wild-type patients. Grade 3 or higher treatment-related adverse events occurred in three patients (14.3%).ConclusionsRegorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.

Abstract Background Various methods are used to reconstruct the skull after microvascular decompression, giving their own advantages and disadvantages. The objective of this study was to evaluate the efficacy of using autologous bone fragments for skull reconstruction after microvascular decompression. Methods The clinical and follow-up data of 145 patients who underwent microvascular decompression and skull reconstruction using autologous bone fragments in our hospital from September 2020 to September 2021 were retrospectively analyzed. Results Three patients (2.06%) had delayed wound healing after surgery and were discharged after wound cleaning. No patient developed postoperative cerebrospinal fluid leakage, incisional dehiscence, or intracranial infection. Eighty-five (58.62%) patients underwent follow-up cranial computed tomography at 1 year postoperatively, showed excellent skull reconstruction. And, the longer the follow-up period, the more satisfactory the cranial repair. Two patients underwent re-operation for recurrence of hemifacial spasm, and intraoperative observation revealed that the initial skull defect was filled with new skull bone. Conclusion The use of autologous bone fragments for skull reconstruction after microvascular decompression is safe and feasible, with few postoperative wound complications and excellent long-term repair results.

We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA.

With the emergence of novel variants, there have been widespread COVID-19 infections in the Chinese mainland recently. Compared to ancestral COVID-19 variants, Omicron variants become more infectious, but less virulent. Previous studies have recommended postponing non-emergency surgery for at least 4–8 weeks after COVID-19 infection. However, delayed surgery has been shown to be associated with tumor progression and worse overall survival for cancer patients. Here, we examined surgery risk and optimal timing for colorectal cancer patients with perioperative COVID-19 infection. A total of 211 patients who underwent colorectal cancer surgery from 1 October 2022 to 20 January 2023 at Xinhua Hospital were included. In addition, COVID-19-infected patients were further categorized into three groups based on infected time (early post-COVID-19 group, late post-COVID-19 group and postoperative COVID-19 group). The complication rate in patients with COVID-19 infection was 26.3%, which was significantly higher than in control patients (8.4%). The most common complications in COVID-19-infected patients were pneumonia, ileus and sepsis. Patients who underwent surgery close to the time of infection had increased surgery risks, whereas surgery performed over 1 week after recovery from COVID-19 did not increase the risk of postoperative complications. In conclusion, surgery performed during or near the time of COVID-19 infection is associated with an increased risk of developing postoperative complications. We recommend that the safe period for patients with recent COVID-19 infection in colorectal cancer surgery be at least 1 week after recovery from COVID-19.

Aim. In clinical practice, a considerable proportion of patients with chronic hepatitis B (CHB) who do not conform to any immune status are considered to be in the “indeterminate phase”. In this study, we aim to study the clinical distribution characteristics and identification of significant liver inflammation in patients in indeterminate phase. Methods. This study retrospectively analyze clinical data of 1226 patients with CHB at two medical centers in Zhejiang province. According to American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidance, CHB can be divided into four phases: immune-tolerant phase, HBeAg-positive immune active phase, inactive phase, and HBeAg-negative immune active phase. Liver inflammation grade was evaluated using the Scheuer scoring system, and significant liver inflammation was defined as G≥2. Results. The distribution of different immune status was as follows: 259 (21.1%) patients in immune-tolerant phase, 365 (29.8%) patients in HBeAg-positive immune active phase, 128 (10.4%) patients in inactive phase, and 33 (2.7%) patients in HBeAg-negative immune active phase. However, 441 (36.0%) patients did not meet any of the above immune phases, which were defined as indeterminate phase. Significant liver inflammation (54.1%) was common in CHB patients with indeterminate phase. Prothrombin time (PT), platelet count (PLT), alanine aminotransferase (ALT), and hepatitis B virus (HBV)-DNA were associated with significant inflammation. Conclusions. The results of this study showed that about 36.0% of patients were divided into indeterminate phase. The proportion of patients with significant inflammation in indeterminate phase and liver inflammation becomes more severe with aggravation of fibrosis stage. PT, PLT, ALT, and HBV-DNA may have a significant correlation with severe inflammation and prognosis of CHB.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Rehmanniae Radix Preparata (RRP) has been used to management of osteoporotic pain in traditional Chinese medicine trials. However, how RRP exhibits the anti-nociceptive effect remains largely unknown. To this end, estrogen-deficient rats were orally gavaged with aqueous RRP extracts for 12 weeks. The tail flick latency, Von-Frey and formalin assays were employed to evaluate pain sensitization. The administration of RRP alleviates allodynia and hyperalgesia in estrogen-deficient rats. These alterations were associated with a decrease in the expression of substance P (SP), neurokinin-1 receptor (NK-1R), phospho (p)-PI3K, p-protein kinase B (Akt), and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the spinal cord. In addition, RRP improves bone quality in the rats. These results suggest RRP could attenuate pain sensitization and improve bone quality through regulation of PI3K/Akt/TRPV1 signaling pathway during menopause stages. And RRP is considered a novel source of anti-osteoporotic pain drug candidates.

In the original publication [...]

ObjectiveThis study aims to evaluate the impact of the inferior petrosal veins (IPVs) on operational exploration and to analyze related anatomic features.MethodsA total of 317 patients were retrospectively studied. Surgical outcomes and postoperative complications were analyzed, and patients were divided into two groups according to whether the IPV was sacrificed or preserved. The diameter of the IPV was also recorded during operation. Furthermore, the position where the IPV drained into the jugular bulb was recorded in each patient, and the influence of different injection points on the operation was analyzed.ResultsIPVs were conclusively identified in 242/317 (76.3%) of patients, with 110/242 (45.5%) of patients categorized as “IPV sacrifice” versus 132/242 (54.5%) categorized as “IPV preservation.” IPV diameter was observed to be 1 mm in 39 cases (16.2%). The position of IPV drainage into the jugular bulb was at the level of the accessory nerve in 163 cases (67.3%), the level of the vagus nerve in 42 cases (17.4%), and the level of the glossopharyngeal nerve or above in 37 cases (15.3%). The diameters of IPV in the sacrifice group were mainly less than 1 mm (94.5% vs. 75%, P 1 mm.

Colorectal cancer (CRC) is the most prevalent type of malignant tumor of the gastrointestinal tract. In the current study, we characterized the landscape of genomic alterations in CRC patients. Based on the results of whole-exome sequencing (WES), we identified 31 significantly mutated genes. Among them, several genes including TP53, KRAS, APC, PI3KCA, and BRAF were reported as significantly mutated genes in previous studies. In the current study, the most frequently mutated gene was TP53, which encodes tumor suppressor p53, affecting approximately 60% of CRC patients. In addition, we performed the expression profiles of significantly mutated genes between the normal group and tumor groups and identified 20 differentially expressed genes (DEGs); among them, CSMD3, DCHS2, LRP2, RYR2, and ZFHX4 were significantly negatively correlated with PFS. Moreover, consensus clustering analysis for CRC based on the expression of significantly somatic mutated genes was performed. In total, three subtypes of CRC were identified in CRC, including cluster1 (n = 453), cluster2 (n = 158), and cluster 3 (n = 9), based on expression level of significantly somatic mutated genes. Clinicopathological features analysis showed subtype C1 had the longest progression-free survival (PFS) with median time of 8.2 years, while subtypes C2 and C3 had 4.1 and 2.7 years of PFS, respectively. Moreover, we found three subtypes related to tumor infiltration depth, lymph node metastasis, and distant metastasis. Immune infiltration analysis showed the tumor infiltration levels of B cell native, T cell CD8+, T cell CD4+ memory activated, T cell gamma delta, NK cell resting, macrophage M0, macrophage M2, myeloid dendritic cell activated, mast cell activated, and mast cell resting significantly changed among the three groups, demonstrating the three subgroups classified by 22 somatically significantly mutated genes had a high capacity to differentiate patients with different immune statuses, which is helpful for the prediction of immunotherapy response of CRC patients. Our findings could provide novel potential predictive indicators for CRC prognosis and therapy targets for CRC immunotherapy.

ObjectiveDisorder of consciousness (DoC) resulting from severe brain injury is characterized by cortical and subcortical dysconnectivity. However, research on seed-based effective connectivity (EC) of DoC might be questioned as to the heterogeneity of prior assumptions.MethodsFunctional MRI data of 16 DoC patients and 16 demographically matched healthy individuals were analyzed. Revised coma recovery scale (CRS-R) scores of patients were acquired. Seed-based d mapping permutation of subject images (SDM-PSI) of meta-analysis was performed to quantitatively synthesize results from neuroimaging studies that evaluated resting-state functional activity in DoC patients. Spectral dynamic causal modeling (spDCM) was used to assess how EC altered between brain regions in DoC patients compared to healthy individuals.ResultsWe found increased effective connectivity in left striatum and decreased effective connectivity in bilateral precuneus (preCUN)/posterior cingulate cortex (PCC), bilateral midcingulate cortex and left middle frontal gyrus in DoC compared with the healthy controls. The resulting pattern of interaction in DoC indicated disrupted connection and disturbance of posterior parietal-frontal-striatum, and reduced self-inhibition of preCUN/PCC. The strength of self-inhibition of preCUN/PCC was negatively correlated with the total score of CRS-R.ConclusionThis impaired EC in DoC may underlie disruption in the posterior parietal-frontal-striatum circuit, particularly damage to the cortico-striatal connection and possible loss of preCUN/PCC function as the main regulatory hub.

The incidence of chronic alcoholism leading to central and peripheral nervous system damage has been increasing year-to-year. The purpose of this study is to explore the effects of aminooxyacetic acid on hippocampus mitochondria in rats with chronic alcoholism and analyze learning and memory-related genes. Sixty male Sprague Dawley rats were randomly divided into three groups. Except for the control group, each group was fed with the water containing (v/v) 6% alcohol for 28 days. After 14 days, rats in the treatment group were intraperitoneally injected daily for 14 days with aminooxyacetic acid. High throughput sequencing was combined and tested for learning and memory abilities, Hydrogen sulfide content, catalase activity in mitochondria, and the expression of F-actin in the hippocampus of the rats in each group. Compared with the control group, the learning and memory abilities of rats with chronic alcoholism were significantly impaired, mitochondria contained vacuoles, hydrogen sulfide increased, but catalase activity and F-actin content were significantly decreased, After treatment with aminooxyacetic acid, mitochondrial morphology improved, hydrogen sulfide content was decreased, while catalase activity and F-actin expression of in hippocampus were increased. This indicates that aminooxyacetic acid may improve learning and memory in rats with chronic alcoholism, and the mechanism is related to decreased hydrogen sulfide content and an increase of both catalase activity and F-actin level in the hippocampus, thereby reducing the damage of alcohol to mitochondria and neurons.

Hyperuricemia (HUA) is a kind of metabolic disease with high incidence that still needs new countermeasures. Apigenin has uric-lowering and kidney-protective activities, but how apigenin attenuates HUA and renal injury remains largely unexploited. To this end, an acute HUA mouse model was established by intraperitoneal injection of potassium oxazinate and oral administration with hypoxanthine for 7 consecutive days. Apigenin intervention decreased serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-18 (IL-18), liver xanthine oxidase (XOD), and urine protein levels, and increased serum interleukin-10 (IL-10) and urine UA and CRE levels in HUA mice. Moreover, administration of apigenin to HUA mice prevented renal injury, decreased renal glucose transporter 9 (GLUT9) and urate anion transporter 1 (URAT1) levels, and increased renal organic anion transporter 1 (OAT1). These alterations were associated with an inhibition of IL-6, phospho-janus kinase 2 (P-JAK2), phospho-signal transducer, and activator of transcription 3 (P-STAT3), and suppression of cytokine signaling 3 (SOCS3) expression in the kidneys. Additionally, the molecular docking results showed that apigenin had strong binding capacity with UA transporters and JAK2 proteins. In summary, apigenin could improve UA metabolism and attenuate renal injury through inhibiting UA production, promoting excretion, and suppressing the JAK2/STAT3 signaling pathway in HUA mice. The results suggest that apigenin may be a suitable drug candidate for management of HUA and its associated renal injury.

BackgroundEmerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents of several malignant tumors and affect the tumor microenvironment and cancer evolution. Here, we investigate the prognostic value of PMNs and NETs for recurrence in patients with cervical cancer.MethodsThe study comprised 126 cervical cancer patients who were retrospectively enrolled. CD66b+ neutrophils and myeloperoxidase/citrullinated histone H3 (MPO/H3Cit)-labeled NETs were assessed by immunofluorescence, and the relationships with clinical and histopathologic features and patient outcome were evaluated.ResultsThe highest density of CD66b+ neutrophils were observed in the stromal compartment (median 55 cells/mm2). Above median densities of stromal CD66b+ neutrophils and NETs were significantly associated with short recurrence-free survival (RFS) (P = 0.041 and P = 0.006, respectively). Multivariate analysis identified high clinical stage (hazard ratio [HR] 6.40; 95% confidence interval [CI] 3.51-11.64; P < 0.001), lymph node metastases (HR 4.69; 95% CI 3.09-9.66; P = 0.006) and high density of NETs (HR 2.66; 95% CI 1.21-5.82; P = 0.015) as independent prognostic factors for short RFS, whereas a high density of CD66b+ neutrophils was not significant. Patients with a high NET density showed worse recurrence status in every stage, but the difference was only significant for stage I (P = 0.042), not stages II, III, or IV (all P > 0.05). Combining stromal NET density and the tumor, nodes, metastasis (TNM) staging system had better prognostic accuracy for cervical cancer than the TNM staging system alone at five and six years respectively (P = 0.010 and P = 0.023).ConclusionStromal NET density is an independent prognostic factor for RFS in cervical cancer. Combining NETs with the TNM staging system may further improve prognostic stratification.

A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD.

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU).Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis.Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05).Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.

The simply prepared CuMgAl hydrotalcite (CuMgAl-LDH) has been developed as an efficient catalyst for the aerobic oxidation of ethylbenzene to acetophenone in the presence of N-Hydroxyphthalimide (NHPI). Various alkyl arenes could be tolerated under the selected reaction conditions. The kinetic study showed that the oxidation of ethylbenzene is a first-order reaction over CuMgAl-LDH. The mechanism study indicated that CuMgAl-LDH could accelerate not only the conversion of ethylbenzene, but also the transformation of the alcohol intermediate to ketone. The positive effect of surface basicity of the catalyst on the reaction has been observed in the aerobic oxidation of the ethylbenzene.

This article presents a compact 3 dB waveguide directional coupler with full waveguide bandwidth. It consists of a pair of rectangular waveguides with stairs structures in the coupling region. The waveguides are placed parallel to each other along their broad wall, which has a rectangular aperture array. The compact size, broad bandwidth, good in-band coupling flatness, and good return loss are achieved by using the proposed structure. For verification purposes, a prototype of the proposed coupler was designed, manufactured, and measured. The experimental results show that over the full waveguide bandwidth a return loss of input port better than 17.46 dB, coupling strength varying between −2.74 dB and −3.80 dB, power-split unbalance within 0.76 dB, and an isolation better than 20.82 dB were obtained. The length of the coupling region was only 15.82 mm.

A passive wireless impedance-loaded orthogonal frequency-coded (OFC) surface acoustic wave (SAW) sensor for wireless sensor networks was proposed in this paper. One of the chips on OFC SAW tag is connected to an external sensor, which could cause a phase shift in the time response of the corresponding part on the SAW device. The phase shift corresponds to the sensed quantity, which could be temperature, strain, vibration, pressure, etc. The OFC SAW tag is isolated by a proper package from the direct effect of the measurand on the device’s response which could avoid the multiple measurands coupling. The simultaneous work of multiple sensors is guaranteed by orthogonal frequency coding. By processing the response based on an extended matched filter algorithm, sensing information of the specific coded OFC device can be extracted from the superimposed response of multiple independent encoded sensors. Compared to previous methods, the proposed method can produce a more flexible passive (battery-free) wireless sensor suitable for large-scale wireless sensor networks. Simulation and experimental results demonstrate the effectiveness of the sensor.

Over the past few years, nanomaterials toxicology has emerged as a new exciting field in which theoretical and experimental studies of toxicity of nanomaterials have become a focus, and the importance of carbon nanotubes (CNTs), graphene oxide (GO), quantum dots (QDs), magnetic nanoparticles (MNPs), and amorphous silica nanoparticles (ASN) as special nanomaterials to the fundamental development in biomedical engineering has begun to be recognized. In particular, interaction between nanomaterials and nucleic acids, proteins or cells, animals, environment, etc. has become a new interdisciplinary frontier, there is an increasing need for a more systematic study of the basic issues involved in nanomaterials toxicity and potential toxicity-reducing methods, great advances have been and are being made in nanomaterials’ biological effects and application in disease diagnosis and therapy. Here we review some of the main advances in this field over past few years, and discuss about the concepts, issues, approaches, and challenges, with the aim of stimulating a broader interest in studying the toxicological mechanism of nanomaterials and potential toxicity- eliminating measurement.

Up to date, application of nanomaterials and nanotechnology has made great advances. Many novel nanomaterials with unique properties are increasingly being exploited to apply for biosensors, improving the property of biosensor and making them higher selectivity and sensitivity, less response time and lower detective limitation. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches, and challenges, with the amin of promting to develop nanomaterials-based biosensor nanotechnology and improving their application in disease diagnosis and biosafety examination.

Single-mode spectral analysis (SMSA) is a simple procedure efficiently used to evaluate the seismic demands of base-isolated bridges, particularly suitable for the design of simple bridges or preliminary design of complex bridges. However, bridge design codes, notably the Canadian code CSA-S6:19 (CSA-S6 2019), specify many limitations on the use of the method for final design. This paper evaluates the performance of SMSA and the efficiency of its limits of application as specified in the current codes through the results of a parametric study. The hysteretic properties of seismic isolation systems and the stiffness of bridge substructures are varied. Seismic demands predicted by SMSA and nonlinear time-history analyses (NLTHAs) are then compared, both inside and outside the current specified limit range in CSA-S6:19 (CSA-S6 2019). Results show that the most effective application conditions are those related to the maximum equivalent viscous damping and minimum restoring force. The upper limits of the effective period and the post-elastic period can be ignored. Further, to complement SMSA, a relation is proposed to estimate the expected residual displacement as a function of the restoring force at the design displacement. Regression relations allowing estimating the expected mean and confidence interval of the relative displacement deviation predicted by SMSA from that based on NLTHA are also proposed. Key words: seismic base isolation, bridges, single-mode spectral analysis, equivalent linear model, residual displacement, expected error L'analyse spectrale unimodale (<< SMSA >>) est une procedure simple et efficace utilisee pour evaluer les reponses sismiques maximales des ponts isoles a la base, particulierement adaptee a la conception de ponts simples ou a la conception preliminaire de ponts complexes. Toutefois, les codes de conception des ponts, notamment le Code canadien sur le calcul des ponts routiers CSA-S6:19 (CSA-S6 2019), specifient de nombreuses limites quant a l'utilisation de la methode pour la conception finale. Le present document evalue le rendement de la SMSA et l'efficacite de ses limites d'application precisees dans les codes actuels au moyen des resultats d'une etude parametrique. Les proprietes hysteretiques des systemes d'isolation sismique et la rigidite des sous-structures des ponts sont variees. Les reponses sismiques maximales prevues par la SMSA et les analyses temporelles non lineaires (<< NLTHA >>) sont ensuite comparees, a l'interieur et a l'exterieur de la plage de limites specifiees dans le Code canadien sur le calcul des ponts routiers. Les resultats montrent que les conditions d'application les plus efficaces sont celles liees a l'amortissement visqueux equivalent maximal et a la force de rappel minimale. Les limites superieures de la periode effective et de la periode post-elastique peuvent etre ignorees. De plus, pour completer la SMSA, on propose une relation pour estimer le deplacement residuel prevu en fonction de la force de rappel, et ce, au deplacement de conception. Des relations de regression permettant d'estimer la moyenne et l'intervalle de confiance de l'ecart relatif du deplacement prevu par la SMSA par rapport a celui fonde sur la NLTHA sont egalement proposees. [Traduit par la Redaction] Mots-cles : isolation sismique a la base, ponts, analyse spectrale unimodale, modele lineaire equivalent, deplacement residuel, erreur attendue, 1. Introduction Seismic base isolation (SBI) is commonly used to protect bridge structures in areas prone to moderate and high seismic activity. By shifting the fundamental frequency of the structure [...]