Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers.

BACKGROUND: The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. AIM: To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma. METHODS: We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs). RESULTS: Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group. CONCLUSION: In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Porphyromonas gingivalis-induced hematogenous disseminated severe pneumonia: a case report.

Porphyromonas gingivalis, a gram-negative oral anaerobe among more than more than 500 bacterial species that colonizing the oral cavity, is involved in the pathogenesis and prototypic polybacterial consortium of periodontitis. It is mainly found in oral infections and rarely present in other organ diseases. Here, we describe a 43-year-old man with underlying diabetes who developed hematogenous disseminated severe pneumonia after P. gingivalis had invaded the blood. Next-generation sequencing of early alveolar lavage fluid and blood samples confirmed the diagnosis. The patient's lung infection improved after targeted antimicrobial treatment. He was successfully weaned from ventilatory support and transferred to the general ward. This case illustrates bacterial entry into the bloodstream of a patient with diabetes who had periodontal disease but did not maintain oral hygiene, leading to severe pneumonia. Periodontal disease is often ignored by the public, and it is difficult for critical care physicians to link severe pneumonia with periodontal disease. Thus, this case represents an important warning to critical care clinicians.

[Bisulfite Promoted Minute Fe2+-Activated Peroxydisulfate for Paracetamol Degradation].

Fe2+ has been commonly selected to activate peroxydisulfate(PDS) for sulfate radical(SO4-·) generation because of its eco-friendly, cost-effective, and high activity characteristics. However, Fe2+ can be rapidly oxidized to Fe3+ in the reaction, leading to poor utilization of iron for PDS activation. Further, a fairly high concentration of Fe2+ is generally required and may cause iron sludge production and secondary pollution. In this study, a minute Fe2+-activated PDS system induced by bisulfite(BS) was used to degrade paracetamol(APAP) in water. The results showed that the Fe2+-PDS system could be enhanced by the circulation of Fe2+-Fe3+ with the injection of BS and by keeping Fe2+ at a high concentration. Under the optimal conditions(PDS=0.6 mol·L-1; BS=0.4 mol·L-1; Fe2+=10 µmol·L-1; pH=4), 100% APAP(4 µmol·L-1) was removed within 180 s. The degradation rate of APAP increased with the increase in BS(0-0.6 mmol·L-1) and PDS(0.2-1.5 mmol·L-1) concentration, and a modest Fe2+ concentration could accelerate APAP removal. Co-existing substances inhibited the APAP removal and followed the order of HCO3->HPO42->Cl->NO3->humic acid(HA). Based on the quenching experiments and electron paramagnetic resonance spectroscopy test, SO4-· was shown to be the primary reactive species for APAP decomposition in the BS-Fe2+-PDS process. Three-dimensional fluorescence spectroscopy revealed that APAP intermediates had fluorescence characteristics. Moreover, five intermediates were identified, and the probable APAP degradation pathways were proposed. The removal efficiencies of APAP were lower in real waters than that in ultrapure water. Nevertheless, the removal effect was greatly improved after a prolonged reaction time. All results indicated that the BS-Fe2+-PDS system could be a promising method for organic pollutant treatment.

[Characteristics of Microplastic-derived Dissolved Organic Matter(MPDOM) and the Complexation Between MPDOM and Sulfadiazine/Cu2].

Microplastic-derived dissolved organic matter(MPDOM) during the aging process could be complexed with organic pollutants, heavy metals, and other contaminants and thus affect their migration and transformation. In this study, two types of microplastics, polyethylene terephthalate(PET) and polystyrene(PS), were selected to investigate the spectral properties of MPDOM and their effect on the complexation between MPDOM and sulfadiazine(SDZ)/copper ion(Cu2+) using the fluorescence quenching method, various spectroscopic analysis techniques, and the Ryan-Weber quenching model. The results of UV-vis absorption spectroscopy analysis showed that the molecular weight of the two MPDOMs decreased; the aromaticity and humification increased; and the carboxyl, carbonyl, hydroxyl, and ester substituents on aromatic rings increased after aging. The fluorescence quenching process between MPDOM and SDZ/Cu2+ was static quenching. After quenching, the aromaticity and humification of the two MPDOMs were similar, and the molecular weights were comparable. Combined with three-dimensional fluorescence spectra and parallel factor analysis, two humic-like components and one protein-like component were identified. In addition, the protein-like components of MPDOM reacted preferentially with SDZ and were more sensitive to Cu2+. The results of the Ryan-Weber quenching model revealed that the binding ability of humic-like components to PET-DOM was higher in both SDZ and Cu2+ quenching systems, but the binding ability of MPDOM in the SDZ quenching system was generally stronger than that in the Cu2+ system.

Effects of comprehensive nursing intervention on pressure ulcer after traumatic brain injury surgery: A meta-analysis.

Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16-0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11-0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63-24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.

Safety and efficacy of mesenchymal stem cells in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease-19 (COVID-19) is a zoonotic disease that has become a global pandemic. The fast evolution of the COVID-19 pandemic and persist problems make COVID-19 highly infectious; publicly accessible literature and other sources of information continue to expand in volume. The mesenchymal stem cells (MSCs) therapy efficacy for COVID-19 is debatable. OBJECTIVE: This systematic review and meta-analysis (SRMA) aimed to evaluate the usefulness of MSCs in treating COVID-19. METHODS: Relevant publications were retrieved from databases up to April 30, 2022. In the case of dichotomous data, the 95% confidence intervals (CIs) and pooled risk ratio (RR) were estimated with a random effects model (REM) or fixed effects model (FEM). The pooled mean difference (MD) and 95% CIs were calculated with REM or FEM in continuous data. In the outcomes, studies with insufficient or unusable data were reported descriptively. RESULTS: A total of eight randomized controlled trials (RCTs) with 464 people were chosen for this SRMA. Relative to the control group, mortality was significantly lower in the MSCs group (RR: 0.66, 95% CI: 0.44, 0.99, Z = 2.01, p = .04); other secondary outcomes, such as the clinical symptom improvement rate improved in the MSCs group (RR: 1.44, 95% CI: 1.05, 1.99, Z = 2.24, p = .03), clinical symptom improvement time (MD: -4.01, 95% CI: -6.33, -1.68, Z = 3.38, p = .0007), C-reactive protein (CRP) (MD: -39.16, 95% CI: -44.39, -33.94, Z = 14.70, p < .00001) and days to hospital discharge (MD: -3.83, 95% CI: -6.19, -1.48, Z = 3.19, p = .001) reduced significantly in MSCs group. However, the adverse reaction incidence did not change significantly. CONCLUSIONS: MSCs are a viable therapy option for COVID-19 because of their safety and potential efficacy. With no significant adverse effects, MSCs can reduce mortality, clinical symptom improvement time, and days to hospital discharge, improve clinical symptoms, and reduce inflammatory cytokines CRP in COVID-19. However, further high-quality clinical studies are required to confirm these results.

TYROBP-positive endothelial cell-derived TWEAK as a promoter of osteosarcoma progression: insights from single-cell omics.

Background: Endothelial cells (ECs) play a vital role in promoting the progression of malignant cells, and they exhibit heterogeneity in their phenotypic characteristics. We aimed to explore the initiating cells of ECs in osteosarcoma (OS) and investigate their potential interaction with malignant cells. Method: We obtained scRNA-seq data from 6 OS patients, and datasets were batch-corrected to minimize variations among samples. Pseudotime analysis was performed to investigate the origin of differentiation of ECs. CellChat was employed to examine the potential communication between endothelial cells and malignant cells, and gene regulatory network analysis was performed to identify transcription factor activity changes during the conversion process. Importantly, we generated TYROBP-positive ECs in vitro and investigated its role in OS cell lines. Finally, we explored the prognosis of specific ECs cluster and their impact on the tumor microenvironment (TME) at the bulk transcriptome level. Results: The results showed that TYROBP-positive ECs may play a crucial role in initiating the differentiation of ECs. TYROBOP-positive endothelial cells (ECs) exhibited the strongest crosstalk with malignant cells, likely mediated by TWEAK, a multifunctional cytokine. TYROBP-positive ECs exhibited significant expression of TME-related genes, unique metabolic and immunological profiles. Importantly, OS patients with low enrichment of TYROBP-positive ECs had better prognoses and a lower risk of metastasis. Finally, vitro assays confirmed that TWEAK was significantly increased in ECs-conditioned medium (ECs-CM) when TYROBP was over-expressed in EC cells, and could promote the proliferation and migration of OS cells. Conclusion: We concluded that TYROBP-positive ECs may be the initiating cells and play a crucial role in the promotion of malignant cell progression. TYROBP-positive ECs have a unique metabolic and immunological profile and may interact with malignant cells through the secretion of TWEAK.

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis.

Background: In patients undergoing hemodialysis, intracerebral hemorrhage (ICH) is the main cause of mortality among stroke subtypes. It is unclear whether, along with traditional cardiovascular risk factors, the risk factors unique to the uraemic environment, such as the abnormal metabolism of intact parathyroid hormone (iPTH), can contribute to the risk of ICH in these patients. Methods: This retrospective case-control study included 25 patients undergoing hemodialysis with ICH at a single center between 30 June 2015 and 10 October 2022. The controls were 95 patients undergoing maintenance hemodialysis treated at the same dialysis center in July 2020. We compared the characteristics of patients with ICH with those of the control group to identify factors that contributed to the development of ICH. Results: Intracerebral hemorrhage (ICH) was located in the basal ganglia (14/25), cerebellum (6/25), and brainstem (6/25) in 25 patients. A total of 17 patients died in the first 16 days due to neurological complications. Univariate analysis showed significant differences in systolic BP, diastolic BP, iPTH, and alkaline phosphatase between the two groups (p < 0.05). Multivariate logistic regression analysis showed that higher systolic BP (OR, 1.053; 95% CI, 1.018-1.090; p = 0.003) and higher iPTH (OR, 1.007; 95% CI, 1.003-1.012; p = 0.001) were associated with the onset of ICH. ICH was predicted by systolic BP and iPTH by receiver operating characteristic (ROC) curve analysis, with areas under the curve (AUCs) of 0.732 and 0.624, respectively. The optimal cutoffs for systolic BP and iPTH were 151.9 mmHg and 295.4 pg./ml, respectively. Restricted cubic spline showed that the shape of the association of iPTH with the risk of ICH was approximately J-shaped (P for non-linearity <0.05). Conclusion: Higher systolic BP and abnormal iPTH metabolism might be associated with ICH in patients undergoing hemodialysis. Comprehensive control of hypertension and iPTH may be a fundamental preventive strategy for ICH in these patients.

[Mn/Al-layered Double Oxide-loaded Biochar Reduced the Toxic Effects of Heavy Metals on Ryegrass in Soil].

The combined pollution of heavy metal Cu and Cd in soil induced by the e-waste dismantling process has become a severe problem. To deal with this issue, crab shell biochar (BC) and Mn/Al-layered double oxide-loaded crab shell biochar (LDO/BC) were prepared using coprecipitation and co-pyrolysis of discarded crab shells and manganese aluminum salt. The experimental results showed that not only were the soil pH, available phosphorus, available potassium, and soil enzymatic activity enhanced, but the contents of DTPA-Cu and DTPA-Cd in the soil were also reduced after remediation by BC and LDO/BC. Microbial community analysis indicated that BC-1% could promote the relative abundance of Gemmatimonadota and Acidobacteriota; meanwhile, LDO/BC-1% could promote the relative abundance of Proteobacteria, which could reduce the accumulation of Cd in plants. Ryegrass was planted for further investigating the toxic effect of heavy metals in soil after remediation. The results demonstrated that after remediating with BC-5% and LDO/BC-1%, ryegrass grew more vigorously and with a lower content of the heavy metals Cu and Cd in the plants than that of CK, and the germination rate increased by 29% and 60%, respectively. Further, LDO/BC-1% had a more excellent remediation performance than that of the other groups, and the Mn in LDO/BC could reduce the content of heavy metal Cd adsorbed by ryegrass in soil.

[Effect of Colloids in Sediment and Soil on Their Sorption Behavior of Chloramphenicol].

Natural colloids (NCs) are ubiquitous in sediments and soils, which could affect the environmental fate of antibiotics. Focusing on chloramphenicol (CAP), different sources of the sediments and soil samples were selected to research the sorption capacity of NCs with different relative molecular weights towards CAP, as well as the impactors, combined with a multi-method approach including cross-flow ultrafiltration, dynamic light scattering, UV-visible absorption spectroscopy, and three-dimensional excitation-emission matrix fluorescence spectroscopy. The results revealed that the low molecular weight (LMW) of NCs was associated with a low autochthonous origin and a higher humification degree. The high molecular weight (HMW) of NCs were mainly terrestrial sources, and the aromatic rings contained more oxygen-containing functional groups such as carboxyl, hydroxyl, and carbonyl groups. Four fluorescence components were identified using the parallel factor analysis model, and the humic-like substances were the primary fluorescent components. Moreover, based on batch experiments, the study investigated the sorption behavior of CAP by the different fractions of the solid samples. The results showed that the sorption processes of CAP were well fitted by the linear model and Freundlich model. The average sorption rate of CAP by the original solid samples and the solid samples with removed organic and inorganic carbon were 4.46%, 3.93%, and 6.61%, respectively, indicating that organic carbon played an important role in the sorption behavior of CAP. The results of the sorption experiments indicated that CAP was more easily adsorbed on the LMW NCs that had a high degree of humification and a more aliphatic chain on the aromatic rings. In addition, tryptophan-like protein substances in NCs showed the inhibiting effect on the sorption progress of CAP. Redundancy analysis indicated that the sorption of CAP by NCs in sediment and soil was mainly related to the source, aromatics, oxygen functional groups on aromatic rings, humification degree, and humic-like substances of NCs.

Efficacy and Safety of Convalescence Plasma Therapy in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Background: The coronavirus disease 2019 (COVID-19) has outbroken into a global pandemic. The death rate for hospital patients varied between 11% and 15%. Although COVID-19 is extremely contagious and has a high fatality rate, the amount of knowledge available in the published literature and public sources is rapidly growing. The efficacy of convalescent plasma (CP) therapy for COVID-19 is controversial. Objective: This meta-analysis was designed to assess the efficacy of CP therapy for COVID-19 through a literature survey. Methods: Until August 30, 2021, a literature search was undertaken in Pubmed, Embase, Web of Science, Cochrane Central Register of Controlling Trials (Central), and China National Knowledge Infrastructure databases. The Risk Ratio (RR) and 95% confidence intervals (CIs) were pooled using a fixed or random effect model in dichotomous data. Mean difference (MD) and 95% confidence intervals (CIs) were pooled using a fixed or random effect model in continuous data. Studies with missing or unsuitable data were presented descriptively in the outcomes. Results: In total, thirteen randomized controlled trials (RCTs) were selected for the present meta-analysis, which included a total of 13232 participants. Our results revealed that the CP group has lower mortality compared to the control group, and there was a statistically significant difference (RR: 0.70, 95% CI: 0.55, 0.89, Z = 2.92, P = 0.004 < 0.01); other secondary outcomes such as the shortness of breath symptom improved significantly in CP group (RR:1.48, 95% CI: 1.13, 1.93, Z = 2.85, P = 0.004 < 0.01), as well as Interleukin-6 (IL-6) (MD: -4.46, 95% CI: -8.28, -0.63, Z = 2.28, P = 0.02 < 0.05) and Ferritin (MD: -447.68, 95% CI: -501.75, -393.6, Z = 16.23, P < 0.00001) are reduced significantly in CP group. However, there was no statistically significant change in the ventilator withdrawal rate, imaging results improvement, or days to hospital discharge. There was also no substantial difference in viral nucleic acid negative conversion rate and neutralizing antibody-positive conversion rate, as well as the incidence of adverse reactions. Conclusions: The safety and potential efficacy of convalescent plasma therapy offer a promising treatment strategy for COVID-19. CP therapy can reduce mortality and improve breath and inflammatory cytokines IL-6 and Ferritin in COVID-19 with no significant increase in adverse reactions. However, it does not affect improving virology indicators. In summary, more high-quality clinical trials are needed to verify the conclusion of the present study.

Case Report: Pulmonary sarcomatoid carcinoma complicating TP53 mutation treated successfully with Tislelizumab combined with Anlotinib-a case report.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen "albumin paclitaxel + cisplatin," but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 105 IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

ß-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway.

Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs for bone regeneration has gained popularity in recent years. ß-ecdysterone is a plant sterol similar to estrogen, that promotes protein synthesis in cells; however, its function in bone regeneration remains unclear. In this study, we investigated the function of ß-ecdysterone on osteoblast differentiation and bone regeneration in vitro and in vivo. MC3T3-E1 cells were used to test the function of ß-ecdysterone on osteoblast differentiation and bone regeneration in vitro. The results of the Cell Counting Kit-8 assay suggested that the proliferation of MC3T3-E1 cells was promoted by ß-ecdysterone. Furthermore, ß-ecdysterone influenced the expression of osteogenesis-related genes, and the bone regeneration capacity of MC3T3-E1 cells was detected by polymerase chain reaction, the alkaline phosphatase (ALP) test, and the alizarin red test. ß-ecdysterone could upregulate the expression of osteoblastic-related genes, and promoted ALP activity and the formation of calcium nodules. We also determined that ß-ecdysterone increased the mRNA and protein levels of components of the BMP-2/Smad/Runx2/Osterix pathway. DNA sequencing further confirmed these target effects. ß-ecdysterone promoted bone formation by enhancing gene expression of the BMP-2/Smad/Runx2/Osterix signaling pathway and by enrichment biological processes. For in vivo experiments, a femoral condyle defect model was constructed by drilling a bone defect measuring 3 mm in diameter and 4 mm in depth in the femoral condyle of 8-week-old Sprague Dawley male rats. This model was used to further assess the bone regenerative functions of ß-ecdysterone. The results of micro-computed tomography showed that ß-ecdysterone could accelerate bone regeneration, exhibiting higher bone volume, bone surface, and bone mineral density at each observation time point. Immunohistochemistry confirmed that the ß-ecdysterone also increased the expression of collagen, osteocalcin, and bone morphogenetic protein-2 in the experiment group at 4 and 8 weeks. In conclusion, ß-ecdysterone is a new bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. This newly discovered function of ß-ecdysterone has revealed a new direction of osteogenic differentiation and has provided novel therapeutic strategies for treating bone defects.

Association Between White Matter Hyperintensities and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objectives: Previous studies of the associations between white matter hyperintensities (WMH) and chronic kidney disease (CKD) were still conflicting; therefore, our study aimed to conduct a systematic review of all of the available research on this topic and a meta-analysis of the association between WMH and CKD among observational studies. Setting and Design: Systematic review and meta-analysis. Outcome Measures: Severity of WMH. Methods and Participants: All relevant studies in public databases were examined until 15 November 2020. Two independent reviewers assessed all the included studies using the Cross-Sectional/Prevalence Study Quality (CSSQ) scale, and then literature review and meta-analyses were undertaken. Results: We pooled the odds ratio (OR) for the presence of WMH, periventricular hyperintensities (PVH), and deep subcortical white matter hyperintensities (DWMH) of patients with CKD vs. non-CKD patients by subgroup analysis, and the results obtained were WMH OR 2.07, 95% CI [1.58, 2.70], PVH OR 2.41, 95% CI [1.90, 3.05], and DWMH OR 2.11, 95% CI [1.60, 2.80], respectively. The main outcome showed that patients with CKD were more likely to have WMH in the brain compared to the normal controls. Another meta-analysis showed a statistically significant decline in renal function in patients with moderate to severe WMH compared with those with no to mild WMH. Conclusions: The findings indicated that patients with CKD were more likely to experience WMH than demographically matched controls. On the other hand, patients with moderate to severe WMH in the brain had poor renal function more frequently than those with no to mild WMH.

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19.

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public's awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research.

Clinical analysis of 60 children with pelvic fracture and associated injuries: an observational study.

BACKGROUND: The injury mechanism of a pelvic fracture is primarily high-energy injury, and it is easily combined with injuries to other tissues and organs. This study aimed to investigate the clinical effectiveness of early diagnosis and treatment of pelvic fractures and associated injuries in children. METHODS: The diagnosis and treatment of 60 children with pelvic fractures and associated injuries who were admitted to our hospital from January 2005 to December 2016 were retrospectively analyzed. Among these patients, 36 were male, and 24 were female. The patients' ages ranged within 2-15 years, with an average of 7.6 years old. The pelvic fractures were classified based on the Torode and Zieg classification; among the patients, 12 had type I, 16 had type II, 20 had type III, and 12 had type IV. All patients received early diagnosis, immediate anti-shock measures, aggressive treatment of associated injuries, and early reduction and fixation of the pelvic fractures after admission. RESULTS: Of the 60 patients, 28 had injuries caused by traffic accidents, 26 had injuries caused by falling from high places, and 16 had injuries caused by compressing or crushing. Eight patients had unilateral pubic bone fracture or pubic symphysis separation that involved posterior pelvic fracture or sacroiliac joint separation, and two had fractures that affected the anterior ring or acetabulum. Moreover, 26 patients had hemorrhagic shock, 18 had traumatic brain injury, 14 had fractures at other sites, 8 had pelvic large vessel injuries, 8 had ipsilateral femoral and proximal femoral fractures, 8 had retroperitoneal hematoma, 8 had urinary system injury, 6 had perineal laceration and vaginal trauma, 6 had spinal cord injury, 4 had intestinal injuries, 4 had soft tissue contusions, and 4 had sacral nerve injury. During the follow-up (average: 48 months), six children died. The evaluation results of the curative effect were excellent in 32 children, good in 18, and poor in 4; the 'excellent' and 'good' rate was 92.5% (50/54). CONCLUSION: Early diagnosis, reduction, and fixation and timely treatment of associated injuries might achieve better clinical efficacy and are worthy of clinical promotion. KEY WORDS: Associated Injuries, Childhood, Diagnosis, Fracture, Pelvic, Treatment.

[Structural Analysis of Salivary Bacterial and Fungal Microbiome in Oral Lichen Planus Patients].

Objective: To explore the differences of oral mycobiome and bacteriome between the healthy controls (H) and oral lichen planus (OLP) patients, and the co-occurrence patterns of the salivary mycobiome and bacteriome and the association with host immunity. Methods: Saliva samples were collected from clinical OLP patients (n=35) and healthy volunteers (n=18). Microbiome DNA was extracted for bacterial 16S rRNA genes sequencing and fungal internal transcribed spacer 2 (ITS2) sequencing. Bioinformatics analysis was performed on the data.The levels of IL-17 and IL-23, two pro-inflammatory cytokines, in the saliva were examined, and their correlation with the bacteria was analyzed. Results: There was no significant difference in the overall community structure of the mycobiome and the bacteriome between OLP patients and healthy controls. The abundance of Prevotellaand Solobacterium in the saliva bacteriome was significantly increased in the OLP group (P<0.05), and the relative abundance of Candidaand Aspergillusin the saliva mycobiome was also significantly increased (P<0.05). The co-occurrence pattern of the salivary mycobiome and bacteriome showed that the aforementioned difference was not related. However, the correlation between Aspergillusand bacteria was altered in the H group and the OLP group, and co-occurrence was reduced in the latter group. The level of IL-17 in the saliva was significantly increased in the OLP group. IL-17 and clinical scores were significantly correlated with the abundance of Porphyromonas. Conclusion: The increased abundance of Prevotella, Solobacterium, Candida, and Aspergillus was associated with the pathogenesis of OLP, and the changes of the microbiome co-occurrence relationship and host immunity may be involved in the pathogenesis of OLP.

[Spectral Characteristics of Dissolved Organic Matter in Sediments from Poyang Lake].

At present, there are few studies on the spectral characteristics of dissolved organic matter (DOM) in the sediments of the Poyang Lake basin. Therefore, excitation-emission matrix spectroscopy (EEMs) technology and ultraviolet-visible spectra combined with the parallel factor analysis (PARAFAC) were applied to investigate the fluorescent components and sources of DOM in sediments from Poyang Lake. The results showed that the DOM in sediments originated from both terrestrial and autochthonous sources with a high humification. Compared with the sub-lakes, the DOM from the main lake was characterized with a higher concentration of colored DOM, larger particle size, and higher aromaticity and humification degree. In addition, four fluorescence components of DOM in sediments were identified by the PARAFAC model, including three humic-like components (C1, C2, and C4) and one protein-like component (C3). The fluorescence intensity of the humic substances in the sub-lakes was higher than those in the main lake. Furthermore, the percentage of fluorescence abundance of C1 was the highest both in the sub-lakes (42%) and main lake (46%). The spatial distribution of the fluorescence intensity of the four components gradually increased from west to east, and the peak values were observed in the Duchang and Nanji Wetland. This may be related to the death of a large number of plants due to the rise in the water level during the wet season and human activities. Principal component analysis showed that although there were no significant differences in the four fluorescent components between the sub-lakes and the main lake, the humification degree of DOM in the sub-lakes was slightly higher than that in the main lake.