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Objective: To investigate the correlation between NOD-like receptor family protein 3 (NLRP3) inflammasome and Golgi protein 73 (GP73) levels and hepatitis B cirrhosis with esophageal varices (EV) rupture. Methods: The subjects of this study were 145 patients with hepatitis B cirrhosis and varices who were treated in our hospital in recent years. Endoscopic examination was performed on the patients. The patients were divided into two groups according to whether there was EV rupture: rupture group and non-rupture group. The correlation between plasma NLRP3 and GP73 levels and hepatitis B cirrhosis with EV rupture was analyzed. Results: Through observation, comparing the levels of NLRP3 and GP73 between the two groups, the levels of NLRP3 and GP73 were significantly higher in the rupture group than in the non-rupture group (P < 0.05). Logistic regression analysis showed that NLRP3 and GP73 levels and Child-Pugh classification were related risk factors of hepatitis B cirrhosis with EV rupture. Conclusion: NLRP3 inflammasome and GP73 levels are closely related to hepatitis B cirrhosis with EV rupture. The corresponding evaluation aids in predicting EV rupture and bleeding in patients with hepatitis B cirrhosis.

ImportanceMild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO.ObjectiveTo evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO.Design, Setting, and ParticipantsIn this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks.InterventionsParticipants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks.Main Outcomes and MeasuresThe primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded.ResultsA total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group.Conclusions and RelevanceThe results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort.Trial RegistrationClinicalTrials.gov Identifier: NCT02203682

To explore the dynamic change of gut microbiota and its predictive role in progression-free survival (PFS) in non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT).Forty-one patients with NSCLC in 2 phase 2 trials (NCT02573506 and NCT03006575) were analyzed. A total of 102 fecal samples were collected at 3 time points (T0, before CCRT; T1, 2 weeks after the initiation of CCRT; and T2, the end of CCRT). Gut microbiota composition and functionality were analyzed by 16S rRNA gene sequencing and shotgun metagenomics, respectively. Alpha diversity, taxonomic composition, and KEGG functional pathways were compared between patients in the long-PFS group (PFS ≥11.0 months) and short-PFS group (PFS11.0 months). A random forest classifier was constructed to identify microbial signature related to PFS. Clinical and microbial factors potentially predictive of PFS were assessed in the univariate and multivariate Cox regression analysis.The abundance of Bacteroidota and Proteobacteria increased, while the abundance of Firmicutes decreased after CCRT. Shannon index (P = .006) and PD index (P = .022) were significantly higher in the long-PFS group than for those in the short-PFS group at T1. The PFS-prediction microbial signature at T1 included unclassified members of the Lanchospiraceae spp., such as NK4A136 and UCG-003 groups, Dorea sp., various strains from within the Eubacterium hallii and E. siraeum groups, and an unclassified member of the Muribaculaceae, which yielded an area under the ROC curve of 0.87. These discriminatory genera mostly belong to phylum Firmicutes/family Clostridia. Multivariate analysis indicated PD index (HR = 8.036, P = .016) and the abundance of Dorea sp. at T1 (HR = 4.186, P = .043) were independent predictors of PFS. The KEGG pathways at T1 overrepresented in the long-PFS group included fatty acid metabolism, fatty acid biosynthesis, and arginine biosynthesis. Those overrepresented in the short-PFS group included lipopolysaccharide biosynthesis, ascorbate and aldarate metabolism, and biosynthesis of vancomycin group antibiotics.Gut microbiota composition and functionality at 2 weeks after the initiation of CCRT were associated with PFS in NSCLC. Further research is needed to confirm these results.

In order to investigate the absorption and retention characteristics of condensed water at different soil layers in the bare desertification area at the bottom of a receding lake in Hoh Xil, Qinghai Province, the characteristics of condensate variation, condensate formation time, condensate volume, and its absorption capacity were investigated in July 2021 using a micro-osmometer. The research area was the artificial water retention layer and bare ground of the exposed sandy bottom formed under the influence of the warming–wetting trend that occurs when water recedes in the salt lake area of the Qinghai-Tibet Plateau, as well as the two conditions of underpass and underseal. According to the results, the time of condensation generation during the observation period in the salt lake area of Hoh Xil begins at about 0:00 and ends at about 10:00. The artificial water retention layer had little influence on the condensation generation time, and the trend of the condensation rate is the same. The unidirectional condensation phenomenon of water vapor in the near-surface air at a depth range of 0–5 cm when an artificial water retention layer is applied is clearly superior to that of other layers; accordingly, its frequency of condensation phenomenon is also the highest. The amount of condensed soil water vapor from the lower part of the ground when an artificial water retention layer is applied at depth ranges of 0–5 cm, 5–10 cm, and 0–10 cm were 3.60, 6.39, and 10.27 times that of the near-surface air, respectively. The total amount of bidirectional condensed water under the condition of the artificial water retention layer at 0–10 cm was the largest. Conversely, the total amount of condensed water from the near-surface air at a depth range of 0–5 cm under the unidirectional condensation condition was the highest, being twice as great as the total amount of condensed water in other layers, which demonstrates the promoting effect that the artificial water retention layer has on the adsorption of water vapor in the near-surface air. Due to the existence of permafrost in the Qinghai-Tibet Plateau, the heat zero-flux plane in the area of the Salt Lake has a migration range of divergence of approximately 30 cm from the surface to the ground. An analogous humidity coefficient characterizes the retention effect of condensed water in certain areas, which serve to demonstrate how the artificial water retention layer distributed at a depth of 0–5 cm, regardless of bidirectional or unidirectional condensation, has the best capacity for adsorption. The results of this study provide a theoretical basis for condensate absorption capacity and vegetation restoration in the bare ecologically degraded areas of the lake bottom.

Hydrogen sulfide (H

The Notch signaling pathway is related to endothelial dysfunction in coronary atherosclerosis. Our objective was to explore the role of Notch signaling in coronary microvascular dysfunction (CMD). CMD models were constructed by sodium laurate injection in vivo and homocysteine (Hcy) stimulation in vitro. The binding ability of Notch Intracellular Domain (NICD)/H3K9Ac/GCN5 (General Control Non-derepressible 5) to Neuregulin-1 (Nrg-1) promoter was examined by chromatin immunoprecipitation. Immunofluorescence staining was conducted to detect CD31 positive cells, NICD localization, and co-localization of NICD and GCN5. Flow cytometry and Tunel staining were conducted to identify the apoptosis. Hematoxylin and eosin staining, quantitative real-time PCR, western blot, immunohistochemical staining, co-immunoprecipitation, and double luciferase report analysis were also conducted. Notch signaling pathway-related protein levels were decreased, levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4 were enhanced in CMD models. Interference with Nrg-1 further increased the apoptosis in Hcy-induced cardiac microvascular endothelial cells (CMECs). Meanwhile, the activation of the Notch signaling pathway increased the levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4, as well as inhibited the apoptosis induced by Hcy. Furthermore, NICD and histone acetyltransferase enzyme GCN5 could regulate Nrg-1 promoter activity by affecting the expression of acetylation-modified protein H3K9Ac. In addition, NICD also interacted with GCN5. In vivo results also confirmed that the activation of the Notch signal alleviated CMD. Notch signaling pathway regulates Nrg-1 level through synergistic interaction with GCN5, thereby mitigating CMD.

To identify predictive factors for the development of sepsis/septic shock postdecompression of calculi-related ureteric obstruction using the Sequential Organ Failure Assessment (SOFA) score and to compare clinical outcomes and odd risk ratios of patients developing sepsis/septic shock following the insertion of percutaneous nephrostomy (PCN) versus insertion of retrograde ureteral stenting (RUS).Clinico-epidemiological data of patients who underwent PCN and/or RUS in two institutions for calculi-related ureteric obstruction were retrospectively collected from January 2014 to December 2020.537 patients (244 patients in PCN group, 293 patients in RUS group) from both institutions were eligible for analysis based on inclusion and exclusion criteria. Patients with PCN were generally older, had poorer Eastern Cooperative Oncology Group status, and larger obstructive ureteral calculi compared to patients with RUS. Patients with PCN had longer durations of fever, the persistence of elevated total white cell and creatinine, and longer hospitalization stays compared with patients who had undergone RUS. RUS up-front has more unsuccessful interventions compared with PCN. There were no significant differences in the change in SOFA score postintervention between the two interventions. In multivariate analysis, the higher temperature just prior to the intervention (adjusted odds ratio [OR]: 2.039, p = 0.003) and Cardiovascular SOFA score of 1 (adjusted OR:4.037, p = 0.012) were significant independent prognostic factors for the development of septic shock postdecompression of ureteral obstruction.Our study reveals that both interventions have similar overall risk of urosepsis, septic shock and mortality rate. Despite a marginally higher risk of failure, RUS should be considered in patients with lower procedural risk. Patients going for PCN should be counseled for a longer stay. Post-HDU/-ICU monitoring, inotrope support postdecompression should be considered for patients with elevated temperature within 1 h preintervention and cardiovascular SOFA score of 1.

To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P 0.05). In the EA + G group, SBP and DBP decreased (P 0.05), ghrelin concentrations increased (P 0.05), and the concentrations of ET-1 and TXA2 decreased (P 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P 0.05), while PF04628935 reversed these effects.EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis.The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group.The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49,MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.

Pseudomonas aeruginosa is an opportunistic pathogen, and because of its specificity, its treatments appear tricky in postrhinoplasty infections with internal implants. This study summarizes the clinical characteristics and treatment of this type of infections to provide some reference for clinical work.We retrospectively analyzed 10 patients who were diagnosed with a nasal infection of P. aeruginosa after implant nasal augmentation. The results of the bacterial culture and drug sensitivity test of the patients' wound secretions were summarized and analyzed. We summarized the characteristics of the patients' infection and the treatments, and we also summarized the patients' prognosis.In these 10 cases, their implants included rib cartilage and ear cartilage alone, as well as their own cartilage combined with expanded polytetrafluoroethylene and silicone. All patients developed wound infections within 1 month after rhinoplasty, with bacterial cultures of P. aeruginosa . Prolonged use of sensitive antibiotics, as well as wound dressing changes, failed to keep the infection well under control. Patients whose implant was removed and thoroughly debrided within 1 week of infection did not experience any serious complications. In patients who were infected for1 week before surgery to remove the implants, complications such as nasal column necrosis and nasal contracture occurred, and later the nasal repair was performed after multiple surgeries.For bacterial infections in postrhinoplasty wounds with implants, we recommend early bacterial culture. If the infection is clearly P. aeruginosa , the implant should be removed and thoroughly debrided as soon as possible to avoid serious complications.Level IV.

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

Involvement of transcription factor (TFs) in governing genes at transcription or post transcription level is known to have affirmative impact on plant physiological and morphological development, especially during environmental abuse. Application of exogenous proline (Pro) is one among the effective approaches to strengthen plant resistance against stresses. However, Pro-mediated regulative strategies of TFs in responses to the chromium (Cr) in rice plants through the gene interaction network are still not clear. In the current study, Pro-mediated interactive complexity of various TFs (i.e., MYB, NAC, WRKY, bHLH, and bZIP) under hexavalent chromium [Cr(VI)] was investigated using Agilent 4 × 44 K rice gene chip and gene interactive probability model (GIPM). Results showed that exogenous Pro had a negligible effect on Cr uptake in rice plants, while a small positive response in biomass accretion of rice seedlings was observed under Cr(VI)+Pro treatments which was to certain extend greater than single Cr(VI) treatments. Rice microarray analysis showed that Cr(VI) significantly (p 0.05) repressed the expression of TFs in the rice roots and shoots, while the application of exogenous Pro significantly (p 0.05) up-regulated the expression levels of some TFs in rice tissues. Mathematical modularization indicated that Pro-mediated interaction between MYB and NAC carried more weightage than other TFs in rice roots and shoots under Cr(VI) stress. Overall, our study provides convincing evidence to confirm a positive role of exogenous Pro on reducing the negative impact exerted by Cr(VI) on rice plants through regulating expression and interaction of different TFs.

Idiopathic oligoasthenozoospermia (iOAZS) is one of the major causes of male infertility, and the ideal therapies for iOAZS have not been established yet. Traditional Chinese medicine (TCM), including Xianlu oral solution (XL), has been widely used as an adjunct treatment for male infertility in the clinic. However, the underlying mechanisms of XL treatment on iOAZS are still not known. Here, we found that XL treatment has therapeutic effects on ornidazole (ORN)-induced OAZS model rats through the amelioration of testis tissues spermatogenesis and the improvement of sperm concentration and motility. Moreover, XL treatment ameliorated the serum hormone levels, mitochondrial membrane potential, apoptosis status, and oxidative stress status in the testis tissues of iOAZS model rats. These findings identify a potential mechanism underlying the therapeutic effects of Xianlu oral solution on iOAZS, and Xianlu oral solution may be used as a traditional Chinese medicine (TCM) therapy for male infertility caused by iOAZS in clinical practice.

The effect of chronic kidney disease (CKD) on the outcomes of colorectal cancer (CRC) patients after primary CRC surgery is controversial.To analyze whether CKD had specific effect on the outcomes after CRC surgery.We searched the PubMed, Embase, Cochrane Library databases and CNKI, from inception to March 14, 2022. Newcastle-Ottawa Scale was used for the quality assessment in this meta-analysis, and we used RevMan 5.3 was used for data analysis.A total of nine studies including 47771 patients were eligible for this meta-analysis. No significant difference was found in terms of overall postoperative complications [odds ratio (OR) = 1.78, 95%CI: 0.64-4.94,Preexisting CKD was associated with higher rates of pulmonary infection, higher rates of short-term death, and worse OS and poorer DFS following CRC surgery.

Rheumatoid arthritis (RA) is an autoimmune disease with the aberrant differentiation of T helper 17 (Th17) cells. Pyruvate kinase M2 (PKM2), a key enzyme of glycolysis, was associated with Th17 cell differentiation.To investigate the potential therapeutic effects of triptolide (TP) in collagen-induced arthritis (CIA) and Th17 cell differentiation, and elucidated the underlying mechanisms.PKM2 expression and IL-17A production in peripheral blood of RA patients were detected by RT-qPCR or ELISA. Flow cytometry and ELISA were employed to assess the effect of Th17 cell differentiation by TP. PKM2 expression and other glycolysis-related factors were detected using RT-qPCR and Western Blot. PKM2 specific inhibitor Compound 3 K was used to verify the mechanisms. Male DBA/1J mice were divided into control, model, and TP (60 μg/kg) groups to assess the anti-arthritis effect, Th17 cell differentiation and PKM2 expression.PKM2 expression positively correlated with IL-17A production in RA patients. PKM2 expression was increased upon Th17 cell differentiation. Down-regulating PKM2 expression could strongly reduce Th17 cell differentiation. Molecular docking analysis predicted that TP targeted PKM2. TP treatment significantly reduced Th17 cell differentiation, PKM2 expression, pyruvate, and lactate production. In addition, compared with down-regulating PKM2 alone (Compound 3 K treatment), co-treatment with TP and Compound 3 K further significantly decreased PKM2-mediated glycolysis and Th17 cell differentiation. In CIA mice, TP repressed the PKM2-mediated glycolysis and attenuated joint inflammation.TP inhibited Th17 cell differentiation through the inhibition of PKM2-mediated glycolysis. We highlight a novel strategy for the use of TP in RA treatment.

Loess owns the characteristics of collapsibility, disintegration and solubility, which pose a challenge to engineering construction. To examine the shear strength of basalt fiber-reinforced (BFR) loess, consolidated undrained (CU) triaxial tests were conducted to explore the impacts of water content (w), fiber length (FL), fiber content (FC) and cell pressure (σ3) on the shear strength. The microstructure of reinforced loess was constructed using SEM measurements to reveal the reinforcing mechanism of basalt fibers. According to the results, the shear strength model was established taken into account the impacts of FL, FC, and fiber diameter (d) using the regression analysis method. The results showed that the peak strength of BFR soils enhanced as FL, FC, and σ3 increasing, whereas it decreased with increasing of w. The reinforcing mechanism of fibers was divided into a single tensile effect and spatial mesh effect, and the bridging effect transformed the force, which improved the overall ability of composites to resist deformation and damage. The experimental and calculated results agreed well, which suggested the model is suitable for predicting the shear strength of BFR loess. The research results can offer a guideline for the application of BFR loess in the subgrade and slope engineering.

C13H20O4, monoclinic, P21 (no. 4), a = 9.7071(4) Å, b = 7.9026(4) Å, c = 17.3139(7) Å, β = 101.617(4)°, V = 1300.97(10) Å3, Z = 4, Rgt(F) = 0.0428, wRref (F 2) = 0.1145, T = 170 K.

BackgroundTension-type headache (TTH) is the most common neurologic disease worldwide. Acupuncture is commonly applied to treat TTH, but evidence of acupuncture for TTH is contradictory based on previous meta-analyses. Therefore, we conducted this systematic review and meta-analysis to update the evidence of acupuncture for TTH and aimed to provide a valuable reference for clinical application.MethodsWe searched 9 electronic databases from their inceptions to July 1, 2022 for randomized controlled trials (RCTs) of acupuncture for TTH. We also manually searched reference lists and relevant websites, and the experts in this field were consulted for possible eligible studies. Two independent reviewers conducted literature screening, data extraction, and risk of bias assessment. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias of included studies. Subgroup analyses were carried out based on frequency of acupuncture, total sessions, treatment duration, needle retention, types of acupuncture and categories of medication. Data synthesis was performed using Review Manager 5.3 and Stata 16. The Grading of Recommendations Assessment, Development and Evaluation Approach (GRADE) was used to evaluate the certainty of evidence of each outcome. Meanwhile, the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) was used to assess the reporting quality of interventions in clinical trials of acupuncture.Results30 RCTs involving 2,742 participants were included. According to ROB 2, 4 studies were considered as low risk, and the rest studies were some concerns. After treatment, compared with sham acupuncture, acupuncture had greater effect in improvement of responder rate [3 RCTs, RR = 1.30, 95%CI (1.13, 1.50), I2 = 2%, moderate certainty] and headache frequency [5 RCTs, SMD = −0.85, 95%CI (−1.58, −0.12), I2 = 94%, very low certainty]. In contrast to medication, acupuncture was more effective to reduce pain intensity [9 RCTs, SMD = −0.62, 95%CI (−0.86, −0.38), I2 = 63%, low certainty]. Adverse events were evaluated in 16 trials, and no serious event associated with acupuncture occurred.ConclusionsAcupuncture may be an effective and safe treatment for TTH patients. Due to low or very low certainty of evidence and high heterogeneity, more rigorous RCTs are needed to verify the effect and safety of acupuncture in the management of TTH.

IFN-γ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGF-β promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGF-β inhibits IFN-γ signaling in immune cells. We thus sought to determine whether TGF-β affects IFN-γ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGF-β stimulation of tumor cells increased SHP1 phosphatase activity in an AKT-Smad3-dependent manner, decreased IFN-γ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion-related molecules, e.g., PD-L1, IDO1, HVEM, and Gal-9. In a lung cancer mouse model, dual blockade of TGF-β and PD-L1 led to superior antitumor activity and prolonged survival compared to anti-PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti-PD-L1 monotherapy, dual TGF-β and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared to that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti-PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFN-γ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGF-β on the development of IFN-γ-mediated tumor resistance to immunotherapy.

Stroke has become a major disease that seriously threatens human health due to its high incidence and disability rates. Most patients undergo upper limb motor dysfunction after stroke, which significantly impairs the ability of stroke survivors in their activities of daily living (ADL). Robots provide an optional solution for stroke rehabilitation by attending therapy in the hospital and the community, however, the rehabilitation robot still has difficulty in providing needed assistance interactively like human clinicians in conventional therapy. For safe and rehabilitation training, a human-robot interaction space reshaping method was proposed based on the recovery states of patients. According to different recovery states, we designed seven experimental protocols suitable for distinguishing rehabilitation training sessions. To achieve assist-as-needed (AAN) control, a PSO-SVM classification model and an LSTM-KF regression model were introduced to recognize the motor ability of patients with electromyography (EMG) and kinematic data, and a region controller for interaction space shaping was studied. Ten groups of offline and online experiments and corresponding data processing were conducted, and the machine learning and AAN control results were presented, which ensured the effective and the safe upper limb rehabilitation training. To discuss the human-robot interaction in different training stages and sessions, we defined a quantified assistance level index that characterizes the rehabilitation needs by considering the engagement of the patients and had the potential to apply in clinical upper limb rehabilitation training.

Osteons are composed of concentric lamellar structure, the concentric lamellae are composed of periodic thin and thick sub-lamellae, and every 5 sub-lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four biomimetic models with different fiber helix angles were established and fabricated according to the micro-nano structure of osteon. The effects of the fiber periodic helical structure on impact characteristic and energy dissipation of multi-layer biomimetic composite were investigated. The calculation results indicated that the stress distribution, contact characteristics and fiber failur during impact, and energy dissipation of the composite are affected by the fiber helix angle. The stress concentration of composite materials under external impact can be effectively improved by adjusting the fiber helix angle when the material composition and material performance parameters are same. Compared with the sample30, the maximum stress of sample60 and sample90 increases by 38.1% and 69.8%, respectively. And the fiber failure analysis results shown that the model with a fiber helix angle of 30° has a better resist impact damage. The drop-weight test results shown that the impact damage area of the specimen with 30° helix angle is smallest among the four types of biomimetic specimens. The periodic helical structure of mineralized collagen fibers in osteon can effectively improve the impact resistance of cortical bone. The research results can provide useful guidance for the design and manufacture of high-performance, impact-resistant biomimetic composite materials.

Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with neuronal death in the hippocampus. Microglia can activate A1 astrocytes by secreting toxins. However, whether NeuroD1 application ameliorates M1microglial polarization through the reduction of A1 astrocyte remains unknown. Methods: 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100µl blood. AAV-NeuroD1-GFP virus was injected to the hippocampus 3 days post-SAH. Neurocognitive function, brain water content, In vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post virus injection. Results: NeuroD1 application dramatically attenuated SAH-induced neuroinflammation by reducing the number of reactive astrocytes and microglia, reversing the transformation of neurotoxic A1 astrocytes and decreasing the secretion of neuroinflammatory cytokines. Interestingly, NeuroD1 significantly boosted the endogenous neurogenesis at the late phase of SAH, likely benefited from the improvement of microenvironment by NeuroD1 treatment after SAH. Notably, hippocampus subgranular zone was one of the brain regions most severely affected by SAH and also the region benefited significantly from NeuroD1 treatment. Above all, NeuroD1 treatment significantly alleviated neurocognitive dysfunction by directly reduction A1astrocytes, followed by the amelioration of M1micorglia, and then restoring endogenous neurogenesis impaired by SAH. Conclusions: NeuroD1 efficiently improved neurocognitive function after SAH by modulating astrocytic and microglial polarization. Moreover, NeuroD1 boosted endogenous neurogenesis at the late phase of SAH, likely thanks to the alleviation of neuroinflammatory microenvironment.

The application scopes of two different reductive perturbation methods to derive the Korteweg–de Vries (KdV) equation and coupled KdV (CKdV) equation in two-temperature-ion dusty plasma are given by using the particle-in-cell (PIC) numerical method in the present paper. It suggests that the reductive perturbation method (RPM) is valid if the amplitude of the CKdV solitary wave is small enough. However, for the KdV solitary wave, RPM is valid not only if the amplitude of the KdV solitary wave is small enough, but also if the nonlinear coefficient of the KdV equation is not tending to zero.

The use of synthetic fungicides against postharvest Alternaria rot adversely affects human health and the environment. In this study, as a safe alternative to fungicides, Bacillus subtilis strain Y17B isolated from soil exhibited significant antifungal activity against Alternaria alternata. Y17B was identified as B. subtilis based on phenotypic identification and 16S rRNA sequence analysis. To reveal the antimicrobial activity of this strain, a PCR-based study detected the presence of antifungal lipopeptide (LP) biosynthetic genes from genomic DNA. UPLC Q TOF mass spectrometry analysis detected the LPs surfactin (m/z 994.64, 1022.68, and 1026.62), iturin (m/z 1043.56), and fengycin (m/z 1491.85) in the extracted LP crude of B. subtilis Y17B. In vitro antagonistic study demonstrated the efficiency of LPs in inhibiting A. alternata growth. Microscopy (SEM and TEM) studies showed the alteration of the morphology of A. alternata in the interaction with LPs. In vivo test results revealed the efficiency of LPs in reducing the growth of the A. alternata pathogen. The overall results highlight the biocontrol potential of LPs produced by B. subtilis Y17B as an effective biological control agent against A. alternata fruit rot of cherry.

BackgroundDepression is a mental health disorder characterized by affective, somatic, and cognitive symptoms. Attention bias modification (ABM) has been widely used to treat depression. However, the results seem inconsistent. We conducted a systematic review and meta-analysis to investigate the efficacy of ABM for depression and to explore the optimal protocol of ABM.MethodsSeven databases were systematically searched from their inceptions to 5 October 2022 to include randomized controlled trials (RCTs) of ABM for depression. Two independent reviewers selected the eligible articles, extracted data, and evaluated the risk of bias using version 2 of the Cochrane risk-of-bias tool (ROB 2.0) for randomized trials. The primary outcome was the evaluation of depressive symptoms using widely accepted and validated scales. The secondary outcomes included rumination and attentional control. Meta-analysis was conducted by using RevMan (version 5.4) and Stata (version 12.0). Subgroup analyses and meta-regressions were performed to identify the source of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).ResultsA total of 19 trials involving 20 datasets (1,262 participants) were included. The overall risk of bias in one study was rated as low risk of bias, three studies were considered as high, and the remaining studies were some concerns. Compared with attention control training (ACT), ABM had a greater effect in the improvement of depression (SMD = −0.48, 95% CI −0.80 to −0.17, I2 = 82%) and rumination (MD = −3.46, 95% CI −6.06 to −0.87, I2 = 0%). No significant differences were observed in the attentional control outcome between ABM and ACT (MD = 3.07, 95% CI −0.52 to 6.65, I2 = 0%). Subgroup analysis demonstrated that adults exhibited a greater decrease in depression scores than adolescents. ABM using the dot-probe task, training target stimulus presented by face, and training directions by left–right were associated with better antidepressant effects. ABM training delivered in the laboratory tended to yield a better effect than those conducted at home. Sensitivity analysis indicated that the results were robust. The certainty of the evidence for all outcomes was low or very low, and publication bias may exist.ConclusionDue to high heterogeneity and limited studies, not enough current evidence supported that ABM could be an effective intervention to relieve depressive symptoms. More rigorous RCTs are required to verify the benefits and to explore the optimal protocol of ABM training for depression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42021279163].

The purpose of enhanced recovery after surgery (ERAS) was to reduce surgical pressure and accelerate postoperative functional recovery. Although the application of biologics in treating inflammatory bowel disease (IBD) has changed treatment strategies, most patients with IBD still require surgery.To evaluate the advantage of ERAS in IBD surgery.The PubMed, EMBASE and Cochrane Library databases were searched from inception to March 21, 2021 to find eligible studies. The primary outcome was postoperative complications, and the secondary outcomes included operation time, time to first flatus, time to bowel movement, postoperative hospital stay and readmission. The PROSPERO registration ID of this meta-analysis is CRD42021238052.A total of eight studies involving 1939 patients were included in this meta-analysis. There were no differences in baseline information between the ERAS group and the non-ERAS group. After pooling up all of the data, no significant difference was found between the ERAS group and the non-ERAS group in terms of postoperative overall complications [odds ratio = 0.82, 95% confidence interval (CI) = 0.66 to 1.02,ERAS was effective for the quicker recovery in IBD surgery and did not lead to increased complications.