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IntroductionThis study aims to explore the incidence of different metastatic patterns in paraaortic lymph nodes and their corresponding survival outcomes in patients with endometrial cancer, as well as to identify the associated risk factors of such metastasis.Material and methodsPubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov were searched from inception to February 10, 2024.The analysis was conducted using R version 4.2.3.ResultsA total of 47 studies involving 33,425 endometrial cancer patients were analyzed. Meta-analysis results revealed that the rate of isolated paraaortic lymph node metastasis, where pelvic lymph nodes were negative but paraaortic lymph nodes were positive (PLN-PAN+), was found to be 2.58% (95% CI 0.0195-0.0329). The rates for PLN+PAN- and PLN+PAN+ were notably higher at 8.54% (95% CI 0.0642-0.1092) and 8.37% (95% CI 0.0613-0.1090), respectively. For clinical stage I EC, the occurrence rate was 5.92% for PLN+PAN- (95% CI 0.0258-0.1032), 1.00% for PLN-PAN+ (95% CI 0.0081-0.0120), and 2.99% for PLN+PAN+ (95% CI 0.0188-0.0431). The survival outcomes indicate a decreasing trend from the PLN-PAN+ and PLN+PAN- groups to the PLN+PAN+ group. Additionally, the survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. The analysis indicated that pelvic lymph node metastasis (OR 16.72, 95% CI 10.03-27.86), myometrial invasion ≥50% (OR 5.18, 95% CI 3.09-8.69), lymph-vascular space invasion (LVSI) (OR 3.46, 95% CI 2.49-4.81), cervical invasion (OR 4.00, 95% CI 2.09-7.66), and non-endometrioid cancer (OR 2.39, 95% CI 1.17-4.86) were risk factors for paraaortic lymph node metastasis.ConclusionsIsolated paraaortic lymph node metastasis, though relatively rare, can still occur even in clinical stage I endometrial cancer. The survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. Even in patients with negative pelvic lymph nodes, careful consideration should be given to the possibility of paraaortic lymph node metastasis, especially in those with high-risk factors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024503959.

ObjectiveTo summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1.MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0.ResultsA total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size ≥4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node ≥ 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1.ConclusionsThe migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions.Protocol registrationCRD 42023451793.

BackgroundThe aim of this study was to determine the relationship between the lymph node ratio (LNR) and the prognostic values of gynecological cancer.Materials and methodsPubMed, Web of Science, Embase, and the Central Cochrane Library were used to search for studies on LNR and gynecological cancer published before 18 April 2024. The effect measure for meta-analysis of primary outcomes was the hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Pooled HRs and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Sensitivity analysis was applied to evaluate the robustness of the results. The I2 statistic was used to measure heterogeneity. Subgroup analysis and meta-regression were chosen to illustrate the potential heterogeneity of the risk factors for outcomes. Publication bias was assessed using Egger’s test and Begg’s funnel plots.ResultsA total of 34 studies with 23,202 cases were included in this meta-analysis. A meta-analysis found that higher LNR was associated with worse OS (HR = 2.42, 95% CI: 2.07–2.83; I2 = 77.4%, p < 0.05), PFS (HR = 1.97, 95% CI: 1.66-2.32; I2 = 0.00%, p > 0.05), and DFS (HR = 3.18, 95% CI: 2.12–4.76; I2 = 64.3%, p < 0.05). Moreover, meta-analysis revealed significant differences in the association between LNR and OS of cervical cancer (CC) (HR = 2.53, 95% CI: 1.94–3.31; I2 = 72.6%, p < 0.05), ovarian cancer (OC) (HR = 2.05, 95% CI: 1.66–2.54; I2 = 76.7%, p < 0.05), endometrial cancer (EC) (HR = 2.16, 95% CI: 1.48–3.16; I2 = 53.6%, p < 0.05), and vulvar cancer (VC) (HR = 8.13, 95% CI: 3.41–19.43; I2 = 57.2%, p < 0.05).ConclusionWe observed a clear association between higher LNR and poorer prognosis in our study of patients with gynecological cancer. Further prospective studies are warranted to determine the optimal LNR and whether LNR can guide adjuvant therapy use in gynecological cancer. It is essential to conduct further prospective studies to establish the optimal LNR threshold, determine the minimum threshold of lymph node removal, and investigate whether LNR can serve as a reliable marker for guiding adjuvant therapy choices in gynecological cancer.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42024541187.

ObjectiveUterine inflammatory myofibroblastic tumor (UIMT) is a rare tumor of the female reproductive tract with uncertain malignant potential. Previous case series reports have limited our understanding of its diagnosis and treatment. Therefore, we conducted a retrospective analysis of patient files at West China Second University Hospital, Sichuan University to contribute valuable clinical insights to future treatment strategies for this disease.MethodWe comprehensively reviewed patient files of individuals diagnosed with UIMT from January 1st, 2013 to May 1st, 2023.ResultsWe included twenty-seven cases of uterine inflammatory myofibroblastic tumor in our study. Of these, 51.85% (14 cases) were diagnosed with abnormal uterine bleeding, 2 cases had dysmenorrhea, and 12 were unexpectedly diagnosed with suspected uterine fibroids. Ten cases performed total hysterectomy, and 17 cases underwent lesion resection. The positive rate of anaplastic lymphoma kinase (ALK) immunohistochemistry reached 96.3%. After a median of 8 months follow-up time, all patients were disease-free and had survived.ConclusionUterine inflammatory myofibroblastic tumor is easily misdiagnosed, making its diagnosis challenging. Histological features, immunohistochemical results, and molecular confirmation using fluorescence in situ hybridization (FISH) or Next-generation sequencing should be used to confirm the diagnosis. Positive ALK immunohistochemistry, ALK rearrangement, ALK fusion are helpful in diagnosis and ALK inhibitor therapy. Total hysterectomy is often performed for women who do not require fertility, while lesion resection and close follow-up may be considered for those who require fertility preservation.

BackgroundLocoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy.Case reportA 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events.ConclusionThis case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile.

BackgroundObesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links.MethodsSummary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits.ResultsWe found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits.ConclusionsAn intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

BackgroundStudies evaluating the prognostic significance of lymphovascular space invasion (LVSI) in early stage endometrial cancer (EC) are conflicting.ObjectivesTo evaluate whether LVSI identified in stage I EC is associated with worse survival.Search strategyA comprehensive literature search of three databases (Embase, PubMed, and Cochrane) was performed up to April 30th 2023.Selection criteriaCohort studies that have evaluated the relationship between LVSI and prognosis in patients with stage I EC were included.Data collection and analysisTwo authors independently assessed the studies for inclusion, extracted the data of recurrence and survival, and conducted meta-analysis using random effects model. Heterogeneity was evaluated by I2 test.Main resultsA total of 15 studies involving 6,705 patients were included in the meta-analysis. The overall pooled rate of LVSI was 14% [95% confidence interval (CI) CI 0.09-0.18] in stage I EC. LVSI was significantly associated with a higher risk of recurrence [odds ratio (OR) = 2.79, 95%CI 2.07-3.77], reduced overall survival (OS) [hazard ratio (HR)=5.19, 95%CI 3.33-8.07] and recurrence free survival (RFS) [HR = 5.26, 95%CI 3.45-8.02] in stage I EC patients. Similarly, LVSI was associated with an increased risk of recurrence [OR= 3.10, 95%CI 2.13-4.51], decreased OS [HR=5.52, 95%CI 2.16-14.09] and RFS [HR = 4.81, 95%CI 2.34-9.91] in stage IA grade 1 or 2 endometrioid carcinoma patients.ConclusionThe presence of LVSI in stage I EC and in stage IA, grade 1 or 2 endometrioid carcinoma is associated with an increased risk of recurrence, lower OS and RFS.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier 42023425231.

Objective: Real-time accurate venous lesion characterization is needed during endovenous interventions for stent deployment. The goal of this study is to validate a novel device for venoplasty sizing and compliance measurements.Methods: A compliance measuring sizing balloon (CMSB) uses real-time electrical conductance measurements based on Ohm’s Law to measure the venous size and compliance in conjunction with pressure measurement. The sizing accuracy and repeatability of the CMSB system were performed with phantoms on the bench and in a swine model with an induced post thrombotic (PT) stenosis in the common femoral vein of swine.Results: The accuracy and repeatability of the CMSB system were validated with phantom bench studies of known dimensions in the range of venous diameters. In 9 swine (6 experimental and 3 control animals), the luminal cross-sectional areas (CSA) increased heterogeneously along the PT stenosis when the CMSB system was inflated by stepwise pressures. The PT stenosis showed lower compliance compared to the non-PT vein segments (5 mm2 vs. 10 mm2 and 13 mm2 at a pressure change of 40 cm H2O). Compliance had no statistical difference between venous hypertension (VHT) and Control. Compliance at PT stenosis, however, was significantly smaller than that at Control and VHT (p < 0.05, ANOVA).Conclusion: The CMSB system provides accurate, repeatable, real-time measurements of CSA and compliance for assessment of venous lesions to guide interventions. These findings provide the impetus for future first-in-human studies.

This study utilizes China’s records of non-accidental mortality along with twenty-five simulations from the NASA Earth Exchange Global Daily Downscaled Projections to evaluate forthcoming heat stress and heat-related mortality across China across four distinct scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The findings demonstrate a projected escalation in the heat stress index (HSI) throughout China from 2031 to 2100. The most substantial increments compared to the baseline (1995–2014) are observed under SSP5-8.5, indicating a rise of 7.96°C by the year 2100, while under SSP1-2.6, the increase is relatively modest at 1.54°C. Disparities in HSI growth are evident among different subregions, with South China encountering the most significant elevation, whereas Northwest China exhibits the lowest increment. Projected future temperatures align closely with HSI patterns, while relative humidity is anticipated to decrease across the majority of areas. The study’s projections indicate that China’s heat-related mortality is poised to surpass present levels over the forthcoming decades, spanning a range from 215% to 380% from 2031 to 2100. Notably, higher emission scenarios correspond to heightened heat-related mortality. Additionally, the investigation delves into the respective contributions of humidity and temperature to shifts in heat-related mortality. At present, humidity exerts a greater impact on fluctuations in heat-related mortality within China and its subregions. However, with the projected increase in emissions and global warming, temperature is expected to assume a dominant role in shaping these outcomes. In summary, this study underscores the anticipated escalation of heat stress and heat-related mortality across China in the future. It highlights the imperative of emission reduction as a means to mitigate these risks and underscores the variances in susceptibility to heat stress across different regions.

ObjectiveThis study aims to preliminarily assess the oncological and reproductive outcomes of fertility preservation treatment using conization combined with pelvic node evaluation in young patients with early-stage cervical cancer (ECC) through meta-analysis.MethodsIn this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to 0 7/02/2023.ResultsThere were 17 relevant studies with a total of 620 patients included, of which 444 patients received conization combined with pelvic node evaluation. The combined pregnancy rate was 45.4% (95% CI: 0.34–0.57), the combined live birth rate was 33.9% (95% CI: 0.26–0.42), the combined miscarriage rate was 4.8% (95% CI: 0.02–0.092), the combined preterm delivery rate was 5.1% (95% CI: 0.02–0.092), and the combined recurrence rate was 1.9% (95% CI: 0.006–0.035), which did not significantly differ from that of patients who received radical surgery (OR: 0.689, 95% CI: 0.506–0.938).ConclusionCervical conization combined with pelvic lymph node evaluation for fertility preservation in young ECC patients can achieve oncological outcomes similar to radical surgery while improving pregnancy success rates and preserving postoperative fertility. In summary, fertility preservation treatment using cervical conization combined with pelvic lymph node evaluation may be considered as a viable option for young ECC patients with strong fertility preservation desire, resulting in better pregnancy and live birth outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier PROSPERO (CRD42023423432).

ObjectiveBovine pericardium is common biological material for bioprosthetic heart valve. There remains a significant need, however, to improve bioprosthetic valves for longer-term outcomes. This study aims to evaluate the chronic performance of bovine pulmonary visceral pleura (PVP) as bioprosthetic valve cusps.MethodsThe PVP was extracted from the bovine lung and fixed in 0.625% glutaraldehyde overnight at room temperature. The PVP valve cusps for the bioprosthetic valve were tailored using a laser cutter. Three leaflets were sewn onto a nitinol stent. Six PVP bioprosthetic valves were loaded into the test chamber of the heart valve tester to complete 100 million cycles. Six other PVP bioprosthetic valves were transcardially implanted to replace pulmonary artery valve of six pigs. Fluoroscopy and intracardiac echocardiography were used for in vivo assessments. Thrombosis, calcification, inflammation, and fibrosis were evaluated in the terminal study. Histologic analyses were used for evaluations of any degradation or calcification.ResultsAll PVP bioprosthetic valves completed 100 million cycles without significant damage or tears. In vivo assessments showed bioprosthetic valve cusps open and coaptation at four months post-implant. No calcification and thrombotic deposits, inflammation, and fibrosis were observed in the heart or pulmonary artery. The histologic analyses showed complete and compact elastin and collagen fibers in the PVP valve cusps. Calcification-specific stains showed no calcific deposit in the PVP valve cusps.ConclusionsThe accelerated wear test demonstrates suitable mechanical strength of PVP cusps for heart valve. The swine model demonstrates that the PVP valve cusps are promising for valve replacement.

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3 months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

Background and objectivesThe routine application of lymphadenectomy remains a controversial part of surgical staging in malignant ovarian germ-cell tumor (MOGCT). Thus, studies are needed to explore the prognostic significance of lymphadenectomy in MOGCT. The goal of this retrospective study was to report the clinical outcomes of lymph node dissection (LND) and non-LND in MOGCT surgeries.Measurements and main resultsA total of 340 cases of MOGCTs were included: 143 patients (42.1%) had LND and 197 (57.9%) had no LND. The OS rates at 5 years in the LND and non-LND group were 99.3% vs. 100%, respectively. The DFS rates at 5 years in the LND and non-LND group were 88.8% vs. 88.3%. Forty-three patients (12.6%) were successfully pregnant during the postoperative follow-up. There were 44 recurrences (12.9%) and six deaths (1.8%). Stage was an independent prognostic factor for DFS in the multivariate analysis. Pathology was reported as an independent prognostic factor associated with OS in the multivariate analysis.ConclusionLymphadenectomy had no significant influence on the OS (P=0.621) or disease-free survival rate (P=0.332) of patients with MOGCT.

Objective: Left atrial appendage (LAA) occlusion or exclusion has been used in patients with atrial fibrillation to prevent stroke, but the techniques and devices have shortcomings. This study aims to validate the safety and feasibility of a novel LAA inversion procedure.Methods: LAA inversion procedures were done in six pigs. Before the procedure and at 8 weeks postoperatively, heart rate, blood pressure, and electrocardiogram (ECG) were recorded. The serum concentration of atrial natriuretic peptide (ANP) was measured. The LAA was observed and measured by transesophageal echocardiogram (TEE) and intracardiac echocardiogram (ICE). At 8 weeks after LAA inversion, the animal was euthanized. The heart was collected for morphology and histology, including hematoxylin-eosin, Masson trichrome, and immunofluorescence staining.Results: TEE and ICE showed that LAA was inverted, and the inversion was maintained during the 8-week study duration. Food intake, body weight gain, heart rate, blood pressure, ECG, and serum ANP level were comparable before and after the procedure. Morphology and histological staining showed that there was no obvious inflammation or thrombus. Tissue remodeling and fibrosis were observed at the LAA inverted site.Conclusion: The inversion of LAA effectively eliminates the dead space of LAA and thus may reduce the risk of embolic stroke. The novel procedure is safe and feasible, but the efficacy in reducing embolization remains to be demonstrated in future studies.

Scrub typhus is emerging as a global public health threat owing to its increased prevalence and remarkable geographic expansion. However, it remains a neglected disease, and possible influences of meteorological factors on its risk are poorly understood. We conducted the largest-scale research to assess the impact of meteorological factors on scrub typhus in China. Weekly data on scrub typhus cases and meteorological factors were collected across 59 prefecture-level administrative regions from 2006 to 2020. First, we divided these regions into 3 regions and analyzed the epidemiological characteristics of scrub typhus. We then applied the distributed lag nonlinear model, combined with multivariate meta-analysis, to examine the associations between meteorological factors and scrub typhus incidence at the total and regional levels. Subsequently, we identified the critical meteorological predictors of scrub typhus incidence and extracted climate risk windows. We observed distinct epidemiological characteristics across regions, featuring obvious clustering in the East and Southwest with more even distribution and longer epidemic duration in the South. The mean temperature and relative humidity had profound effects on scrub typhus with initial-elevated-descendent patterns. Weather conditions of weekly mean temperatures of 25–33°C and weekly relative humidity of 60–95% were risk windows for scrub typhus. Additionally, the heavy rainfall was associated with sharp increase in scrub typhus incidence. We identified specific climatic signals to detect the epidemic of scrub typhus, which were easily monitored to generalize. Regional heterogeneity should be considered for targeted monitoring and disease control strategies.

NSCLC (non-small cell lung cancer) is one of the most common and lethal malignant tumors, with low 5-year overall survival rate. Curcumol showed antitumor activity in several cancers, but evidence about its effect on NSCLC remains unclear. In the present study, we found that Curcumol markedly inhibited NSCLC cells proliferation, migration and invasion. Endothelial cells are an important part of tumor microenvironment. Tube formation assay and wound healing assay indicated that A549 derived conditioned medium affected HUVECs (human umbilical vein endothelial cells). Mechanistically, Curcumol downregulated the expression of SP1 (specificity protein 1) while upregulated miR-125b-5p, followed by decreasing VEGFA expression in NSCLC cells. Furthermore, overexpression of SP1 partially reversed the inhibitory effect of Curcumol on A549 and H1975 cell viability and VEGFA expression. Inhibition of miR-125b-5p presented similar effect. Interestingly, there was mutual modulation between SP1 and miR-125b-5p. Collectively, our study revealed that Curcumol inhibited cell growth and angiogenesis of NSCLC in vitro and in vivo, possibly through SP1/miR-125b-5p/VEGFA regulatory mechanism. These findings may provide effective therapy strategies for NSCLC treatment.

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography–mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

Objective: Investigation of lymph fluid dynamics in thoracic duct during central venous pressure elevation.Background: Lymphatic flow is affected by elevated central venous pressure (CVP) in congestive heart failure. The changes of thoracic duct (TD) lymph flow have not been studied chronically in the setting of elevated CVP. This study is to investigate fluid dynamics and remodeling of the TD in the elevated CVP animal model.Methods: A flow probe was implanted on the swine TD (n = 6) and tricuspid regurgitation (TR) was created by cutting tricuspid chordae percutaneously. Six swine were used as control group animals. The TD flow was measured for 2 weeks (baseline) before TR and 4 weeks postop-TR surgery. Arterial pressure and CVP were measured. The pressure and flow in the TD were measured percutaneously. Histological and morphological analyses were performed.Results: TR resulted in an increase in CVP from 4.2 ± 2.6 to 10.1 ± 4.3 mmHg (p < 0.05). The lymph flow in the TD increased from 0.78 ± 1.06 before TR to 8.8 ± 4.8 ml/min (p < 0.05) 2 days post-TR and remained plateau for 4 weeks, i.e., the TD flow remained approximately 8–11 fold its baseline. Compared to the 8.1 ± 3.2 mmHg control group, the TD average pressures at the lymphovenous junction increased to 14.6 ± 5.7 mmHg in the TR group (p < 0.05). The TD diameter and wall thickness increased from 3.35 ± 0.37 mm and 0.06 ± 0.01 mm in control to 4.32 ± 0.57 mm and 0.26 ± 0.02 mm (p < 0.05) in the TR group, respectively.Conclusion: The elevated CVP results in a significant increase in TD flow and pressure which causes the TD’s outward remodeling and thickening. Our study implicates that the outward remodeling may result in the TD valve incompetence due to failure coaptation of leaflets.

ObjectivesTo analyze the clinical characteristics, echocardiographic features, and prognosis of fetuses based on three groups of cardiac manifestations associated with maternal anti-Ro and anti-La antibodies in China. This study included three groups: the isolated-arrhythmia, isolated-endocardial fibroelastosis (EFE), and mixed groups.MethodsWe prospectively evaluated 36 fetuses with cardiac manifestations due to maternal anti-Ro and anti-La antibodies from our center between 2016 and 2020 in China. Clinical and echocardiographic data were collected.ResultsThere were 13 patients (36%) in the isolated-arrhythmia group, eight (22%) in the isolated-EFE group, and 15 (42%) in the mixed group. All patients in the isolated-EFE group presented with mild EFE. Severe EFE was identified in four patients (27%) in the mixed group. Atrioventricular block (AVB) was more common in the isolated-arrhythmia group (13, 100%) than in the mixed group (6, 40%; p = 0.001). Moderate-severe mitral regurgitation (p = 0.006), dilated cardiomyopathy (DCM, p = 0.017), and low cardiovascular profile scores (p = 0.013) were more common in the mixed group than in the other two groups. Twenty-one mothers decided to terminate the pregnancy and 15 fetuses were born with regular perinatal treatment. They all survived at 1 year of age. One patient in the isolated-arrhythmia group and two in the mixed group required a pacemaker due to third-degree AVB or atrioventricular junctional rhythm. Five patients in the isolated-EFE group and five in the mixed group had no DCM or heart failure and the location of mild EFE was significantly reduced.ConclusionFetal cardiac manifestations due to maternal anti-Ro and anti-La antibodies can be divided into three groups, i.e., the isolated-arrhythmia, isolated-EFE, and mixed groups. AVB usually occurs in the isolated-arrhythmia group. Severe EFE, moderate-severe mitral regurgitation, and DCM mainly appear in the mixed group. Location of mild EFE significantly reduces after birth and the outcome of fetuses with mild EFE depends on the presence of arrhythmia and its subtypes.

Nitrogen (N) deposition can affect the global ecosystem carbon balance. However, how plant community assembly regulates the ecosystem carbon exchange in response to the N deposition remains largely unclear, especially in alpine meadows. In this study, we conducted a manipulative experiment to examine the impacts of N (ammonium nitrate) addition on ecosystem carbon dioxide (CO2) exchange by changing the plant community assembly and soil properties at an alpine meadow site on the Qinghai–Tibetan Plateau from 2014 to 2018. The N-addition treatments were N0, N7, N20, and N40 (0, 7, 20, and 40 kg N ha–1year–1) during the plant growing season. The net ecosystem CO2 exchange (NEE), gross ecosystem productivity (GEP), and ecosystem respiration (ER) were measured by a static chamber method. Our results showed that the growing-season NEE, ER and GEP increased gradually over time with increasing N-addition rates. On average, the NEE increased significantly by 55.6 and 65.2% in N20 and N40, respectively (p < 0.05). Nitrogen addition also increased forage grass biomass (GB, including sedge and Gramineae) by 74.3 and 122.9% and forb biomass (FB) by 73.4 and 51.4% in N20 and N40, respectively (p < 0.05). There were positive correlations between CO2 fluxes (NEE and GEP) and GB (p < 0.01), and the ER was positively correlated with functional group biomass (GB and FB) and soil available N content (NO3––N and NH4+–N) (p < 0.01). The N-induced shift in the plant community assembly was primarily responsible for the increase in NEE. The increase in GB mainly contributed to the N stimulation of NEE, and FB and the soil available N content had positive effects on ER in response to N addition. Our results highlight that the plant community assembly is critical in regulating the ecosystem carbon exchange response to the N deposition in alpine ecosystems.

Background: Alcoholic liver disease (ALD) is a common chronic liver disorder worldwide, which is detrimental to human health. A preliminary study showed that the total flavonoids within Citrus grandis “Tomentosa” exerted a remarkable effect on the treatment of experimental ALD. However, the active substances of Citrus grandis “Tomentosa” were not elucidated. Rhoifolin (ROF) is a flavonoid component present in high levels. Therefore, this research aimed to evaluate the hepatoprotective effects of ROF and its possible mechanisms.Methods: Molecular docking was performed to analyze the binding energy of ROF to the main target proteins related to ALD. Subsequently, mice were fed ethanol (ETH) for 49 days to establish the chronic alcoholic liver injury models. The liver pathological injury, serum aminotransferase levels, and oxidative stress levels in the liver tissue were measured. Human normal hepatocytes (LO2 cells) were incubated with ETH to construct the alcoholic liver cell model. The inflammatory markers and apoptosis factors were evaluated using real-time PCR and flow cytometry. Finally, the effects of ROF on the CYP2E1 and NF-κB signaling pathways were tested in vitro and in vivo.Results: Molecular docking results demonstrated that ROF was able to successfully dock with the target proteins associated with ALD. In animal studies, ROF attenuated ETH-induced liver damage in mice by decreasing the serum concentrations of AST and ALT, reducing the expression of inflammatory cytokines, and maintaining antioxidant balance in the liver tissue. The in vitro experiments demonstrated that ROF suppressed ETH-induced apoptosis in LO2 cells by promoting Bcl-2 mRNA and inhibiting Bax mRNA and caspase 3 protein expression. ROF decreased the level of LDH, ALT, AST, ROS, and MDA in the supernatant; induced the activity of GSH and SOD; and inhibited TNF-α, IL-6, and IL-1β expression levels. Mechanistically, ROF could significantly downregulate the expression levels of CYP2E1, TLR4, and NF-κB phosphorylation.Conclusion: This study indicates that ROF is the active component within the total flavonoids, which may alleviate ETH-induced liver injury by inhibiting NF-κB phosphorylation. Therefore, ROF may serve as a promising compound for treating ALD.

The COVID-19 pandemic and the consequent restrictive measures adopted by the countries have significantly reduced the capacity of higher education institutions to carry out innovative international teaching and learning activities. This paper provides a short reconstruction of how the seven European universities, members of the Arqus Alliance, handled this challenge. During 2020–21, that is, in full pandemic, the Arqus partners redesigned and implemented a trans-European challenge-based learning (CBL) project involving university students from many disciplinary fields, including social sciences and natural sciences, focused on climate change-related risks in European cities and areas. Based on this experience, a contingent conceptualization of CBL is proposed, comprising eight characteristics, whose effectiveness is then tested against data provided by students who participated in the courses. In this context, the results of a Likert questionnaire distributed to students from participating universities will be discussed. The analysis is meant to provide a deeper understanding of CBL not only as a pedagogical tool for a specific output, but also as a broader learning experience generating outcomes for teachers who plan and deliver CBL activities, and for the beneficiaries of such activities. In other words, the article aims to highlight some enabling and inhibiting factors of “strategic CBL”—this latter expression is supposed to capture the process of designing and implementing a CBL activity as a CBL practice in itself.

BackgroundLeft main coronary artery atresia (LMCAA) is an extremely rare abnormality and only

Background: Fuzheng Kang’ai decoction (FZKA) has been widely used to treat Non-Small Cell Lung Cancer (NSCLC) patients in China for decades, showing definitively curative effects in clinic. Recently, we found that FZKA could induce NSCLC cell ferroptosis, another type of programmed cell death (PCD), which is totally different from cell apoptosis. Therefore, in the present study, we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis, which is rarely studied in Traditional Chinese Medicine (TCM).Methods: Cell proliferation assay were performed to detect the cell viability. Cell ferroptosis triggered by FZKA was observed by performing lipid peroxidation assay, Fe2+ Ions assay, and mitochondrial ultrastructure by transmission electron microscopy. Ferroptosis inhibitors including liproxstatin-1 and UAMC 3203 were used to block ferroptosis. The ratio of GSH/GSSG was done to measure the alteration of oxidative stress. Western blot and qRT-PCR were carried out to detect the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4 (GPX4) at protein and mRNA levels, respectively. Lentivirus transfection was performed to overexpress GPX4 stably. Animal model was done to verify the effect of FZKA-induced ferroptosis in NSCLC in vivo and immunohistochemistry was done to detect the expression of SLC7A11, SLC3A2 and GPX4 at protein level.Results: First of all, in vitro experiments confirmed the inhibition effect of FZKA on NSCLC cell growth. We then, for the first time, found that FZKA induced NSCLC cell ferroptosis by increasing lipid peroxidation and cellular Fe2+ Ions. Moreover, characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy. Mechanistically, GPX4, as a key inhibitor of lipid peroxidation, was greatly suppressed by FZKA treatment both at protein and mRNA levels. Furthermore, system xc− (SLC7A11 and SLC3A2) were found to be suppressed and a decreased GSH/GSSG ratio was observed at the same time when treated with FZKA. Notably, overexpressing GPX4 reversed the effect of FZKA-induced NSCLC cell ferroptosis significantly. Finally, the above effect was validated using animal model in vivo.Conclusion: Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis, providing a novel molecular mechanism by which FZKA treats NSCLC.

AimsTo assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population.MethodsThis prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed.ResultsThe rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04).ConclusionsThis study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Gut microbiome and heredity are two important factors affecting the intramuscular fat (IMF) of cattle, excluding age, sex, and nutrition. This study aimed at deciphering these two differences by analyzing the gut microbiome and intramuscular differentially expressed genes (DEGs) in the Angus and Chinese Simmental cattle. Feces and longissimus dorsi were collected from the two groups of animals (n = 20/group) for multiomics analysis. Angus holds a significantly higher diversity than Chinese Simmental, and the relative abundance of Roseburia, Prevotella, Coprococcus, etc., was obviously higher in Angus. Chinese Simmental had higher levels of isobutyrate, isovalerate, and valerate, although similar levels of acetate, propionate, and butyrate were observed for the two groups. The DEGs upregulated in Chinese Simmental were mainly involved in immune and inflammatory responses, while those in Angus were associated with the regulation of muscle system and myofibril. We finally identified 17 species, including Eubacterium rectale, etc., which were positively correlated to muscle and fat metabolism genes (MSTN, MYLPF, TNNT3, and FABP3/4) and illustrate the associations between them. Our study unveils the gut microbial differences and significant DEGs as well as their associations between the two breeds, providing valuable guidance for future mechanism research and development of intervention strategies to improve meat quality.

Objective: The goal of the study is to determine the structural characteristics, mechanical properties, cytotoxicity, and biocompatibility of the pulmonary visceral pleura (PVP).Background: Collagen and elastin are the major components of the extracellular matrix. The PVP has an abundance of elastin and collagen that can serve as a potential biomaterial for clinical repair and reconstructions.Methods: The PVP was processed from swine and bovine lungs. Chemical analyses were used to determine collagen and elastin contents in the PVPs. Immunofluorescence microscopy was used to analyze the structure of the PVP. The stress–strain relationships and stress relaxation were determined by using the planar uniaxial test. The cytotoxicity of the PVP was tested in cultured cells. In in vivo evaluations, the PVP was implanted in the sciatic nerve and skin of rats.Results: Collagen and elastin contents are abundant in the PVP with larger proportions of elastin than in the bovine pericardium and porcine small intestinal submucosa. A microstructural analysis revealed that the elastin fibers were distributed throughout the PVP and the collagen was distributed mainly in the mesothelial basal lamina. The incremental moduli in stress–strain curves and relaxation moduli in the Maxwell–Wiechert model of PVP were approximately one-tenth of the bovine pericardium and small intestinal submucosa. The minimal cytotoxicity of the PVP was demonstrated. The axons proliferated in the PVP conduit guidance from proximal to distal sciatic nerves of rats. The neo-skin regenerated under the PVP skin substitute within 4 weeks.Conclusions: The PVP is composed of abundant collagen and elastin. The structural characteristics and mechanical compliance of the PVP render a suitable biological material for repair/reconstruction.

As a C4 energy crop widely planted all over the world, sweet sorghum is mainly used in sugar making and brewing. Fresh sweet sorghum stalks contain many natural ingredients that have antioxidant properties and can significantly inhibit the growth of foodborne pathogens. In this study, the polyphenols in sweet sorghum were extracted by acid ethanol and ion precipitation, and the types of polyphenols were determined by HPLC-MS. The polyphenol content in fresh sweet sorghum stalks was 5.77 mg/g after process optimization with 18 types of phenolic acids identified. The extract had a total antioxidant capacity of 9.4 μmol Trolox/mL. Polyphenol extract of sweet sorghum displayed antibacterial activity against Staphylococcus aureus, Escherichia coli, Listeria spp., and Salmonella spp. The extract increased the conductivity of cell suspensions by destroying the membrane structure, resulting in leakage of cell electrolytes. Changes in bacterial morphology and internal structure were indicated. The data describe an optimized process to extract polyphenols from sweet sorghum stalks and the methodology to identify the major components within the extract. The data provide a novel option for the comprehensive utilization of fresh sweet sorghum stalks.

ObjectiveSingle-port laparoscopy has become a feasible and safe approach for the management of benign adnexal masses during pregnancy. To our knowledge, there are few reports on the feasibility and safety of single-port laparoscopy for adnexal mass removal during pregnancy. Our study reports the use of single-port laparoscopy in adnexal mass removal during pregnancy in our hospital.MethodsWe included 10 cases of single-port laparoscopic surgery for adnexal mass removal during pregnancy in the West China Second University Hospital between January 2017 and March 2020. Median values were found using SPSS20. When the p-value was

Psoriasis is chronic skin disease and an important health concern. Traditional Chinese Medicine (TCM) has shown great promise in the treatment of psoriasis. However, the correlation between TCM Syndromes and genomics of psoriasis has not been evaluated. Here, we analyzed gene expression profiling of monocytes from psoriasis vulgaris patients with different TCM syndrome types to reveal the molecular basis of different psoriasis syndromes. Of the 62 cases of psoriasis vulgaris recruited, 16, 23, and 23 cases were of blood-heat syndrome, blood stasis syndrome, and blood-dryness syndrome, respectively; 10 healthy controls were recruited as controls. Affymertix’s Gene Chip ®clariom D gene chip was used to detect the gene expression profile of peripheral blood monocytes collected from recruited individuals. Compared with the healthy control group, 1570 genes were up-regulated and 977 genes were down-regulated in the psoriasis vulgaris patients group; 798 genes and 108 genes were up- and down-regulated in the blood-heat syndrome group respectively; 319 and 433 genes were up- and down-regulated in the blood-dryness syndrome group, respectively; and 502 and 179 genes were up-and down-regulated in the blood-stasis syndrome group. Our analyses indicated not only common differential genes and pathways between psoriasis syndrome groups and healthy controls, but also syndrome-specific genes and pathways. The results of this study link the three syndromes at the gene level and will be useful for clarifying the molecular basis of TCM syndromes of psoriasis.Clinical Trial Registration: (http://www.chictr.org.cn/showproj.aspx?proj=4390), identifier (ChiCTR-TRC-14005185).

Psoriasis is a chronic and refractory inflammatory and autoimmune-mediated cutaneous disease affecting approximately 2%–3% of the global population. Most of the current therapies could relieve symptoms rapidly, while the side effects cannot be negligible. Hence, it is urgent to explore much safer and more effective treatments. In the current work, we evaluated the potential beneficial effect of Punica granatum peel polysaccharides (PPPs) in an imiquimod-elicited psoriasis-like mouse model and unraveled their mechanism of action. Firstly, PPPs were isolated from P. granatum peels, and then the molecular weight was determined and monosaccharide analysis was performed. The results revealed that PPPs significantly ameliorated psoriasis-like skin lesions and reduced the Psoriasis Area and Severity Index (PASI) scores and transepidermal water loss (TEWL). PPPs also attenuated the expressions of CD3 and Ki67 in psoriasis-like mouse skin and suppressed the serum or skin levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-1β, IL-8, IL-17, and IL-23. Moreover, PPPs were able to upregulate the mRNA and protein expressions of aquaporin-3 (AQP3) and filaggrin (FLG) in the skin of mice. In addition, PPPs inhibited the NF-κB and STAT3 signaling pathways. Overall, these results indicated that PPPs ameliorated the symptoms of psoriasis through inhibition of the inflammatory cytokines by suppressing the NF-κB and STAT3 signaling pathways and improved skin barrier protection via enhancing AQP3 and FLG. These observations potentially contribute to providing theoretical and experimental evidence for the clinical application of PPPs for psoriasis.

Soil moisture is an important parameter for global soil moisture transport, environmental evaluation, and precision agricultural research. The accurate retrieval of soil moisture in farmland areas using Synthetic Aperture Radar (SAR) depends on the accurate description of surface and SAR parameters. In these parameters, surface roughness and incidence angle are the key factors that affect the accuracy of the soil moisture retrieval model. This article proposes a modified Dubois model to retrieve soil moisture suitable for the bare surface of farmland area. The model eliminates the incidence angle parameters and uses polarization parameters to depict the surface roughness parameters in the Dubois model. To eliminate the incidence angle, the backscattering coefficients gamma0, which eliminates the effect of the incidence angles, are used to replace the sigma0. Under rain and no rain condition, the trend of backscattering coefficients (VH and VV) and cross-polarization ratio (VH-VV) of different soil texture with the soil moisture are compared. Then, the polarization parameter based on VH backscattering coefficients is used to describe surface roughness. The model is evaluated with time-series soil moisture observation data in situ of the study area. The results indicate that the modified model can retrieve soil moisture with high accuracy, and the total RMSE can reach 0.064 cm3cm−3 while the Dubois model is 0.124 cm3cm−3. Under rain and no rain condition, the retrieval accuracy of the modified model is 0.066 cm3cm−3 and 0.063 cm3cm−3. The retrieval accuracy is 0.060 cm3cm−3 and 0.067 cm3cm−3 under high and low incidence angles conditions, respectively. These results indicate that the modified Dubois model can retrieve soil moisture with high accuracy under different conditions.

BackgroundHysteroscopy is becoming a common method for the diagnosis of uterine disorders in developed countries. However, hysteroscopy might worsen the prognosis of endometrial cancer because it could cause cancer dissemination into the peritoneal cavity through the fallopian tubes. Objective: The aim of this systematic review and meta-analysis was to explore the oncological safety of hysteroscopy for early-stage endometrial cancer.Search StrategyEligible studies were obtained from PubMed, Embase, and the Cochrane Library up to September 22, 2020.Selection CriteriaStudies which compared the oncological safety of hysteroscopy with other methods were included.Data Collection and AnalysisA total of 3980 patients were included in this study, of whom1357 patients had undergone hysteroscopy and2623 had not.Main ResultsThere was no significant association between hysteroscopy and worse prognosis in early-stage endometrial cancer [disease-free survival: log risk ratio(logRR) -0.22; 95% confidence interval (CI), -0.54 to 0.1; p=0.97; overall survival: logRR 0.03; 95% CI, -0.05 to 0.11; p=0.02; disease-specific survival: logRR 0.03; 95% CI, -0.03 to 0.10; p=0.00].ConclusionThis study suggests that hysteroscopy is a safe diagnostic and treatment method, and has no significant effect on the prognosis of early-stage endometrial cancer.Systematic Review RegistrationPROSPERO registration number: CRD42020193696.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Further, it has been reported that PD-1 ligands (PD-Ls) contribute to M2 polarization of macrophages and their immunosuppressive effects. Total glucosides of paeony (TGP), originally extracted from Radix Paeoniae Alba, has been approved in China to treat some autoimmune diseases. Here, we investigated the potentially therapeutic effects of TGP on lupus nephritis in a pristane-induced murine model and explored the molecular mechanisms regulating macrophage phenotypes. We found that TGP treatment significantly improved renal function by decreasing the urinary protein and serum creatinine, reducing serum anti-ds-DNA level and ameliorating renal immunopathology. TGP increased the frequency of splenic and peritoneal F4/80+CD11b+CD206+ M2-like macrophages with no any significant effect on F4/80+CD11b+CD86+ M1-like macrophages. Immunofluorescence double-stainings of the renal tissue showed that TGP treatment increased the frequency of F4/80+Arg1+ subset while decreasing the percentage of F4/80+iNOS+ subset. Importantly, TGP treatment increased the percentage of both F4/80+CD11b+PD-L1+ and F4/80+CD11b+PD-L2+ subsets in spleen and peritoneal lavage fluid as well as the kidney. Furthermore, TGP augmented the expressions of CD206, PD-L2 and phosphorylated STAT6 in IL-4-treated Raw264.7 macrophages in vitro while its effects on PD-L2 were abolished by pretreatment of the cells with an inhibitor of STAT6, AS1517499. However, TGP treatment did not affect the expressions of STAT1 and PD-L1 in Raw264.7 macrophages treated with LPS/IFN-γ in vitro, indicating a possibly indirect effect of TGP on PD-L1 expression on macrophages in vivo. Thus, for the first time, we demonstrated that TGP may be a potent drug to treat lupus nephritis by inducing F4/80+CD11b+CD206+ and F4/80+CD11b+PD-L2+ macrophages through IL-4/STAT6/PD-L2 signaling pathway.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, “Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial.” Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

ObjectiveWe evaluated swine and bovine pulmonary visceral pleura (PVP) in artery patch-angioplasty in swine model of high-fat diet.BackgroundArterial patch-angioplasty is frequently used for repair or reconstruction of arteries. An autologous patch is often limited by the number and dimension of donor tissue and can result in donor complications. Furthermore, mechanical mismatch is a cause of poor performance of vascular reconstruction. Here, we introduce a readily available patch biomaterial with similar compliance as native arteries.MethodsThe PVP was peeled from swine and bovine lungs by hydro-dissection. The swine and bovine PVPs were crosslinked with glutaraldehyde and then sterilized. The swine PVP (sPVP) patches were implanted in the carotid and femoral arteries of six Yorkshire pigs that were fed a regular diet and euthanized at 2 and 4 months postoperative. The bovine PVP (bPVP) patches were implanted in the carotid artery of six Yucatan pigs that were fed a high-fat diet and euthanized at 4 months postoperative. Patency was evaluated by ultrasound and angiography. Neo-endothelium and media were evaluated by histologic examination.ResultsAll arteries in patch-angioplasties remained patent with no adhesions, inflammation, or aneurysms. Biomarkers of endothelial cells (e.g., Factor VIII and eNOS) were detected in the neo-endothelial cells. We observed endothelial cell–cell junctions in the confluent neo-endothelium in the PVP patches. Neo-media composed of vascular smooth muscle developed similar as native arteries. In the hypercholesterolemic model, we observed the accumulation of cholesterol in both arterial tissues and in the neo-vascular tissues in the PVP patches. Protein expressions of lipid transport and metabolism (e.g., APOE-1, ABCA, and PACK9) were also observed in both arterial and neo-vascular tissues.ConclusionThe PVP patch-angioplasty overcomes the pitfalls of compliance mismatch of synthetic patches and has a non-thrombogenic surface. The proliferation of vascular cells assembled to generate the neo-endothelium and media in the patch-angioplasties to support long-term patency. The neo-vascular tissue in PVP patch-angioplasty also developed similar cellular functions for lipid transport and metabolism compared with native arteries in hypercholesterolemia.

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

Psoriasis is a chronic inflammatory skin disease that is associated with multiple coexisting conditions. Extensive literature suggests that psoriasis is a T-cell-mediated condition, and its pathogenesis is related to dysfunction of the immune system. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that have suppressive effects on T cells. MDSCs are present at very low levels in healthy individuals but can substantially expand in tumours or inflammatory conditions. PSORI-CM02, a Chinese medical formula designed based on the Chinese medicine theory (Blood Stasis), has been prescribed extensively for psoriasis therapy and shows a stable clinical effect and safety. This study discusses the mechanisms of MDSCs involved in disease development and therapeutic progress. Our data provides evidence that monocytic myeloid-derived suppressor cells (M-MDSCs) play a role in IMQ-induced psoriatic dermatitis. Functional characterization and correlation analysis indicated that MDSCs are positively correlated with Th17 cells. PSORI-CM02 alleviated IMQ-induced psoriatic dermatitis and suppressed the proliferation of Th17 cells via M-MDSC-induced Arg1 upregulation, suggesting M-MDSCs could be a novel therapeutic target for psoriasis, and PSORI-CM02 exerted its effects via the perturbation of M-MDSCs and Th17 cell crosstalk.

The Hainan gibbon (Nomascus hainanus), once widespread across Hainan, China, is now found only in the Bawangling National Nature Reserve. With a remaining population size of 33 individuals, it is the world’s rarest primate. Habitat loss and fragmentation are the primary drivers of Hainan gibbon population decline. In this study, we integrated data based on field investigations and genotype analyses of 10 microsatellite loci (from fecal samples) to assess genetic diversity in this Critically Endangered primate species. We found that the genetic diversity of the Hainan gibbon is extremely low, with 7 of 8 microsatellite loci exhibiting decreased diversity. Additional molecular analyses are consistent with field observations indicating that individuals in groups A, B, and C are closely related, the female–male sex ratios of the offspring deviates significantly from 1:1, and the world’s remaining Hainan gibbon population is expected to experience continued high levels of inbreeding in the future. Given extensive habitat loss (99.9% of its natural range has been deforested) and fragmentation, this rarest ape species faces impending extinction unless corrective measures are implemented immediately.

Psoriasis is a chronic, refractory, systemic inflammatory skin disease. Traditional Chinese medicine (TCM) shows unique advantage in the treatment of psoriasis based on syndrome differentiation. An untargeted high-throughput metabonomics method based on liquid chromatography coupled to mass spectrometry was applied to study the serum metabolic characteristics in different TCM syndrome types in patients with psoriasis vulgaris (PV), and to discover potential serum biomarkers for its pathogenesis on the endogenous metabolite differentiation basis. The serum metabolic profiles of 45 healthy controls and 124 patients with PV (50 in the blood-stasis group, 30 in the blood-heat group, and 44 in the blood-dryness group) were acquired. The raw spectrometric data were processed using multivariate statistical analysis, and 14 biomarkers related to TCM syndrome differentiation and psoriasis types were screened and identified. The blood-stasis syndrome group showed abnormal lipid metabolism, which was characterized by a low level of phosphatidylcholine (PC) and a high level of lysophosphatidylcholine (LPC). We propose that platelet-activating factor can be applied as a potential biomarker in clinical diagnosis and differentiation of PV with blood-stasis syndrome. The difference in the serum metabolites among PV types with different TCM syndromes and healthy control group illustrated the objective material basis in TCM syndrome differentiation and classification of psoriasis.

Mammalian oocytes are enveloped by the zona pellucida (ZP), an extracellular matrix of glycoproteins. In sperm, stimulation with ZP proteins evokes a rapid Ca2+ influx via the sperm-specific, pH-sensitive Ca2+ channel CatSper. However, the physiological role and molecular mechanisms underlying ZP-dependent activation of CatSper are unknown. Here, we delineate the sequence of ZP-signaling events in mouse sperm. We show that ZP proteins evoke a rapid intracellular pHi increase that rests predominantly on Na+/H+ exchange by NHA1 and requires cAMP synthesis by the soluble adenylyl cyclase sAC as well as a sufficiently negative membrane potential set by the spem-specific K+ channel Slo3. The alkaline-activated CatSper channel translates the ZP-induced pHi increase into a Ca2+ response. Our findings reveal the molecular components underlying ZP action on mouse sperm, opening up new avenues for understanding the basic principles of sperm function and, thereby, mammalian fertilization.

Exhaustive exercise has emerged as an important health issue nowadays. This study was designed to assess the metabolite abnormalities of rats after exhaustive exercise and the holistic efficacy of Chinese medicine Sanqi oral solution (SQ). Through exhaustive swimming, the exhaustive exercise model in rats was established. Thirty male Sprague–Dawley rats were randomly divided into control, model, and treatment groups. SQ (12 mL·kg−1·d−1) or 0.9% saline solution was administrated orally by gastric gavage. After 4 weeks, serum samples were collected for biochemical measurements and ultra performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF-MS)-based metabonomic study. It was found that rats with SQ intervention showed longer exhaustive swimming time (P < 0.05) than model rats, with an average of 1,160.36 ± 123.89 s in SQ group and 906.57 ± 172.11 s in model group. Among the biochemical indices, the levels of creatine kinase isoenzyme, lactate dehydrogenase, and glucose of exhaustive exercise rats increased, whereas levels of creatine kinase, urea, triglyceride, and total cholesterol decreased. These biochemical indices came normal after SQ administration, except for triglyceride. Twenty-seven potential biomarkers belonging to sphingolipids, phospholipids, fatty acids, amino acid, and other classes were identified in serum. This study indicated that SQ exerted protective effects on exhaustive exercise by significantly prolonging the swimming endurance time. The metabonomic-based findings of the metabolic state and analysis of potential biomarkers in serum well correlated with biochemical assessment, confirming that SQ had a definite efficacy. Moreover, the shifts in lipid-related metabolites and glycolytic pathway suggested that SQ may serve as a potential supplementation in sports nutrition for its pharmacological effect of regulating energy metabolism as well as improving signal transduction and muscle-cell physiological functions.

A transplanted organ is always rejected in the absence of any immunosuppressive treatment due to vigorous alloimmunity. However, continuously global immunosuppression with a conventional immunosuppressant may result in severe side effects, including nephrotoxicity, tumors and infections. Tregs have been widely used to inhibit allograft rejection, especially in animal models. However, it's well accepted that administration of Tregs alone is not satisfactory in immune-competent wild-type animals. Therefore, it's imperative to promote Treg therapies under the cover of other approaches, including costimulatory blockade. In the present study, we demonstrated that administration of in vitro-expanded CD8+CD122+PD-1+ Tregs synergized with costimulatory blockade of CD40/CD154, but not B7/CD28, to prolong skin allograft survival in wild-type mice and to reduce cellular infiltration in skin allografts as well. Treg treatment and blockade of CD40/CD154, but not B7/CD28, also exhibited an additive effect on suppression of T cell proliferation in vitro and pro-inflammatory cytokine expression in skin allografts. Importantly, blocking B7/CD28, but not CD40/CD154, costimulation decreased the number of transferred CD8+CD122+PD-1+ Tregs and their expression of IL-10 in recipient mice. Furthermore, it's B7/CD28, but not CD40/CD154, costimulatory blockade that dramatically reduced IL-10 production by CD8+CD122+PD-1+ Tregs in vitro, suggesting that B7/CD28, but not CD40/CD154, costimulation is critical for their production of IL-10. Indeed, infusion of IL-10-deficient CD8+CD122+PD-1+ Tregs failed to synergize with anti-CD154 Ab treatment to further prolong allograft survival. Our data may explain why blocking B7/CD28 costimulatory pathway does not boost IL-10-dependent Treg suppression of alloimmunity. Thus, these findings could be implicated in clinical organ transplantation.

Psoriasis is an autoimmune and inflammatory skin disease affecting around 2–3% of the world's population. Patients with psoriasis need extensive treatments with global immunosuppressive agents that may cause severe side effects. Esculetin, a type of coumarins, is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla, which has been used to treat inflammatory and autoimmune diseases in China. However, the antipsoriatic effects of esculetin have not been reported. In this study, we aimed to investigate the effects of esculetin on psoriatic skin inflammation in a mouse model and explored the potential molecular mechanisms underlying its action. We found that esculetin ameliorated the skin lesion and reduced PASI scores as well as weight loss in imiquimod-induced psoriasis-like mice, accompanied with weakened proliferation and differentiation of keratinocytes and T cell infiltration in esculetin-treated psoriatic mice. In addition, esculetin reduced the frequency of CD8+CD44highCD62Llow effector T cells in psoriatic mice. In contrast, it increased the frequency of CD4+Foxp3+ Tregs in both lymph nodes and spleens of the psoriatic mice while promoting the differentiation of CD4+CD25− T cells into CD4+Foxp3+ Tregs in vitro. Interestingly, depleting CD4+Foxp3+ Tregs largely reversed esculetin-mediated reduction in PASI scores, indicating that esculetin attenuates murine psoriasis mainly by inducing CD4+Foxp3+ Tregs. Furthermore, the mRNA levels of proinflammatory cytokines in the psoriatic mouse skin, including IL-6, IL-17A, IL-22, IL-23, TNF-α, and IFN-γ, were dramatically decreased by the treatment with esculetin. Finally, we found that esculetin inhibited the phosphorylation of IKKα and P65 in the psoriatic skin, suggesting that it inhibits the activation of NF-κB signaling. Thus, we have demonstrated that esculetin attenuates psoriasis-like skin lesion in mice and may be a potential therapeutic candidate for the treatment of psoriasis in clinic.

Psoriasis is an autoimmune and inflammatory disease, which is estimated to affect 2–3% of the population in the world. PSORI-CM02 is an empirical formula of Chinese medicine optimized from Yin Xie Ling, which is widely used to treat psoriasis in China for decades. However, its antipsoriatic mechanisms are still not well understood. Here, we explored the therapeutic effects of PSORI-CM02 on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse models and human HaCaT cells. In experiments in vitro, PSORI-CM02 significantly inhibited HaCaT cell proliferation in dose-dependent and time-dependent manners. Furthermore, it hindered the progression of HaCaT cell cycle and arrested HaCaT cells at G1 phase. On the other hand, our in vivo studies demonstrated that PSORI-CM02 dramatically reduced psoriasis area and severity index scores and lesion temperature in imiquimod-induced psoriatic mice. The antioxidative activities of glutathione, catalase, and superoxide dismutase were increased while oxidative activity of malonaldehyde was markedly decreased after treatments with PSORI-CM02. PSORI-CM02 also suppressed the mRNA expression of proinflammatory cytokines, including TNF-α, IL-6, and IL-17, and lowered their protein levels in the serum as well. In addition, PSORI-CM02 could reduce the expression of IKKα and NF-κB in psoriatic skin tissue. It also upregulated the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens and promoted CD4+ CD25+ Treg proliferation in vitro. Taken together, our research demonstrated that PSORI-CM02 inhibited HaCaT cell proliferation by arresting them at G1 phase and alleviated systemic inflammation and psoriasis in mice via altering the oxidative/anti-oxidative status, tipping the balance between Th17 responsiveness and CD4+ Foxp3+ Treg generation, and suppressing the expression of proinflammatory cytokines as well as NF-κB signaling.