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This study was performed to determine the status and ecological risk as well as provide a basis for the prevention and control of antibiotic contamination in the drinking water sources of Anhui Province. Ultra Performance Liquid Chromatography (UPLC-MS/MS) was used to measure the detection rate and concentrations of nine antibiotics, classified as sulfonamides (SAs) or tetracyclines (TCs), in water collected from 51 sampling points and from areas with different seasonal characteristics. The risks of the main antibiotics (Sulfamethoxazole (SMZ), Doxycycline (DOC), Sulfadiazine (SDZ), Sulfamerazine (SM2), Sulfadimethoxine (SDM), Doxycycline (DOC), Tetracycline (TC), Oxytetracyline (OTC), and Chlortetracycline (CTC). to the ecosystem and human beings were evaluated using risk quotients (RQs) and target hazard quotients (THQs), respectively. Nine antibiotics were detected in tap water and surface water at concentrations ranging from 1.71 ng L−1–21.92 ng L−1 and 1.54 ng L−1–78.74 ng L−1, respectively. SMZ and DOC were detected in both tap water and surface water. Their highest detection rates in tap water were 59.1% and 63.6%, respectively, and those in surface water were 81.25% and 43.8%, respectively. SDZ, SMZ, SM2, SDM, DOC, TC, OTC, and CTC were detected in the dry and flood seasons, with levels ranging from 2.43 ng L−1–49.43 ng L−1. Among the detected target antibiotics, SMZ, SM2, TC, OTC, and CTC had higher detection rates. The total concentrations of detected antibiotics were higher in fall than in the other seasons. TC and OTC present in different water sources posed a moderate risk. SDZ present in surface water posed a higher ecological risk than that present in tap water and ground water. Meanwhile, the presence of DOC in tap water and the low risk caused by SDM in surface waters should be emphasized.

The use of organic fertilizers instead of chemical fertilizers can improve soil pH, help to maintain soil health and enable landowners to achieve organic or ecological-status agriculture. Rapeseed cake, sheep manure, and biofungal fertilizer are considered to be effective amendments to improve soil quality. However, there have been few studies on the effects of the three fertilizers on strawberry production, soil physicochemical properties, and inter-root soil microbial community structure. In this study, field experiments were conducted to investigate the differences in strawberry growth, quality, yield, and the structure and diversity of strawberry soil bacterial and fungal communities under four treatments: no organic fertilizer (CK), rapeseed cake organic fertilizer (T1), sheep manure organic fertilizer (T2) and bio-organic fertilizer (algae-optimized bacteria) (T3), the relationship between soil physicochemical properties and soil microbial diversity were analyzed. Our results have shown that these three amendments promoted the growth of strawberry to some extent. The effects of available phosphorus, ammonium nitrogen, sucrase, protease and urease under T2 treatment were significantly increased by 50.62%, 54.14%, 276.50%, 129.47%, 232.61%, and 232.00%, respectively, compared with the control. The soil bacterial and fungi community were the most abundant and diversified under the T2 treatment. Soil physicochemical properties and soil key enzyme activities varied significantly under different fertilizer treatments, with the soil nutrient content and soil carbon and nitrogen metabolizing enzyme activities being highest under T2 treatment. A Pearson correlation analysis showed that soil organic matter was closely related to the diversity of soil microbial communities. A redundancy analysis (RDA) showed that the main variables of the bacterial community included nitrate nitrogen (NN) and rapidly available potassium (RAP), while the main variables of the fungal community included alkaline dissolved nitrogen (ADN) and ammonium nitrogen (AN). Overall, different fertilizers promoted the release and transformation of soil nutrients by affecting the structure and diversity of bacterial and fungal communities in strawberry soils, which was beneficial to the supply of soil nutrients and the improvement of soil quality. The application of sheep manure organic fertilizer had the best soil improvement effect.

BackgroundThe relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR.MethodsIn this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.ResultsWe found that genetically predicted BMR was negatively related to eGFR, (β= −0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (β= −0.040, P = 0.002), weighted median (β= −0.04, P= 5.35×10-11) and weighted mode method (β= −0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= −0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.ConclusionGenetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

The widespread use of antibiotics in animal and human medication has raised global concerns over environmental contamination caused by antibiotic residues. This research investigated the occurrence of 12 kinds of antibiotics belonging to three groups, sulfonamides (SAs), tetracyclines (TCs), and fluoroquinolones (FQs), in chicken manure and the surrounding soil from different chicken farms in Hangzhou, South China, were detected in the samples via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and the contamination characteristics of each type of antibiotic and the correlations between each antibiotic and environmental factors were analyzed to identify the key influencing factors. An ecological risk assessment of antibiotics in the soil environment was conducted using the risk quotient (RQ) method to analyze the potential hazard level. The results indicated that: the total concentration of FQs was much higher than those of SAs and TCs in chicken manures and the soil samples. The mean concentration of FQs (39.17 μg·kg–1), TCs (34.37 μg·kg–1), and SAs (20.24 μg·kg–1) in chicken manure were significantly higher than those in the soil samples. Ciprofloxacin (CIP) was the main antibiotics detected in manure (19.42 μg·kg–1) and the soils samples (near soil: 18.42 μg·kg–1, far soil: 10.29 μg·kg–1), followed by enrofloxacin (ENR), tetracycline (TC), and ofloxacin (OFL). The redundancy analysis (RDA) showed that moisture content (MS), total organic carbon (TOC) and total nitrogen (TN) had a greater influence on the antibiotic concentration in the soil samples. Basis on the calculated risk quotient (RQs) values, the risk assessment indicated Sulfamerazine (SD) and Sulfamethoxazole (SMX) in soil posed a high risk, while trimethoprim (TMP), TC, CIP, and OFL in soils posed a medium or low risk. This research provides control and environmental monitoring data about chicken farms and scientific information that can be used to alleviate antibiotics pollution.

Biochar is a versatile, carbon-rich, organic material that can effectively immobilize Cd in the soil. In this study, peanut shell biochar (SP), maize straw biochar (MS), and bamboo straw biochar (BS) were applied in different proportions to evaluate their effects on the remediation of Cd-contaminated farmland soil and plant growth. The results revealed that both single and mixed applications of biochar substantially increased corn biomass and chlorophyll content compared to the unamended control treatment, while the malondialdehyde (MDA) and proline contents were largely unaffected. The bamboo straw block biochar with maize straw biochar at a mass ratio of 2:1 (DBM) significantly increased the dry total biomass of maize (+107.24% compared to the unamended soil). SP application has highly increased the SPAD value. PB with BS application at a mass ratio of 1:1 (MSB) significantly decreased the soluble sugar content (+21.81% compared to the unamended control soil). Soil pH was increased by the application of biochar alone and in combination with feedstocks. The soil content of Fe/Mn oxide-bound (OX) and exchangeable-bound Cd (EX) was decreased, whereas that of carbonate-bound Cd (CA), residue-bound Cd (RE), and organic-bound Cd (OM) contents increased. The Cd content in corn grains under MSB and SP application was markedly reduced by 42.62% and 31.48%, respectively, compared to the unamended control soil. Overall, MSB and SP applications were effective in improving soil quality and crop growth.

BackgroundIt is now widely accepted that radiotherapy (RT) can provoke a systemic immune response, which gives a strong rationale for the combination of RT and immune checkpoint inhibitors (ICIs). However, RT is a double-edged sword that not only enhances systemic antitumor immune response, but also promotes immunosuppression to some extent. Nevertheless, many aspects regarding the efficacy and safety of this combination therapy remain unknown. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/chemoradiotherapy (CRT) and ICI combination therapy for non-small cell lung cancer (NSCLC) patients.MethodsPubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 28th of February 2022.Results3,652 articles were identified for screening and 25 trials containing 1,645 NSCLC patients were identified. For stage II-III NSCLC, the one- and two-year overall survival (OS) was 83.25% (95% confidence interval (CI): 79.42%-86.75%) and 66.16% (95% CI: 62.3%-69.92%), respectively. For stage IV NSCLC, the one- and two-year OS was 50% and 25%. In our study, the pooled rate of grade 3-5 adverse events (AEs) and grade 5 AEs was 30.18% (95% CI: 10.04%-50.33%, I2: 96.7%) and 2.03% (95% CI: 0.03%-4.04%, I2: 36.8%), respectively. Fatigue (50.97%), dyspnea (46.06%), dysphagia (10%-82.5%), leucopenia (47.6%), anaemia (5%-47.6%), cough (40.09%), esophagitis (38.51%), fever (32.5%-38.1%), neutropenia (12.5%-38.1%), alopecia (35%), nausea (30.51%) and pneumonitis (28.53%) were the most common adverse events for the combined treatment. The incidence of cardiotoxicity (0%-5.00%) was low, but it was associated with a high mortality rate (0%-2.56%). Furthermore, the incidence of pneumonitis was 28.53% (95% CI: 19.22%-38.88%, I2: 92.00%), grade ≥ 3 pneumonitis was 5.82% (95% CI: 3.75%-8.32%, I2: 57.90%) and grade 5 was 0%-4.76%.ConclusionThis study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible. We also summarize details of different RT combinations with ICIs to treat NSCLC. These findings may help guide the design of future trials, the testing of concurrent or sequential combinations for ICIs and RT/CRT could be particularly useful to guide the treatment of NSCLC patients.

IntroductionSepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection; however, its pathophysiology remains unclear. Sepsis-induced neuroinflammation and blood–brain barrier (BBB) disruption are crucial factors in brain function disturbance in SAE. Mast cells (MCs) activation plays an important role in several neuroinflammation models; however, its role in SAE has not been comprehensively investigated.MethodsWe first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. MCs activation was checked using immumohistochemical staining and Toluidine Blue staining. We administrated cromolyn (10mg/ml), a MC stabilizer, to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the interaction of BMVECs and MCs.ResultsResults showed that MCs were overactivated in the hippocampus of CLP-induced SAE mice. Cromolyn intracerebroventricular (i.c.v) injection substantially inhibited the MCs activation and neuroinflammation responses, ameliorated BBB impairment, improved the survival rate and alleviated cognitive dysfunction in septic mice. In vitro experiments, we revealed that MCs activation increased the sensitivity of BMVECs against to lipopolysaccharide (LPS) challenge. Furthermore, we found that the histamine/histamine 1 receptor (H1R) mediated the interaction between MCs and BMVECs, and amplifies the LPS-induced inflammatory responses in BMVECs by modulating the TLR2/4-MAPK signaling pathway.ConclusionsMCs activation could mediate BBB impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.

Heavy metal-containing atmospheric particulate matter (PM) and acid rain (AR) trigger molecular alteration in plants, perturbing metabolites and damaging plant growth. However, the molecular mechanisms of plants under AR along with Cd-containing atmospheric fine particulate matter (PM2.5-Cd) stress remain unknown. In this study, integrated transcriptomics and metabolomics analyses of pak choi (Brassica pekinensis (Lour.) Rupr) exposed to AR (pH3.5) and PM2.5-Cd (500 μg·m−3) stress were performed. Metabolomics analyses revealed that AR-Cd stress mainly affected 42 metabolic pathways, including 451 differentially expressed metabolites (DEMs). RNA-seq identified 735 common differentially expressed genes (DEGs: 557 upregulated and 178 downregulated). Further analysis found several important DEGs (transcription factors, metabolic pathways genes, and signal transduction genes), including WRKY11, WRKY53, WRKY41, MYB73, NAC062, NAC046, HSFA4A, ABCC3, CAXs, GSTs, AZFs, PODs, PME41, CYP707A2, and CDPK32 implying that Cd chelate sequestration into the vacuoles, the antioxidant system, cell wall biosynthesis pathway, and calcium signaling play a critical role in AR damage and Cd detoxification. Conjoint revealed phenylpropanoid and flavonoid biosynthesis pathways with different metabolism patterns, including the key DEM, chlorogenic acids. The results obtained using multiple approaches provide a molecular-scale perspective on plant response to AR-Cd stress.

Background: The cuff catheter is one of the most common routes of vascular access in hemodialysis patients, while severe complications can occur during cuff catheter placement, such as bleeding, hematoma, and artery or vein damage. During catheterization, brachiocephalic vein perforation associated with a mediastinal lesion is rare. Open chest repair is effective for brachiocephalic vein perforation during catheter placement, but it entails a risk of potentially lethal trauma. Interventional treatment can be considered to reduce injury in this context, but relevant reports are limited.Case report: Herein, we describe our experience with a 68-year-old male hemodialyzed patient in whom cuff catheter vascular access was required for regular hemodialysis. He complained of mild pain in the left side of his chest during cuff catheter placement. The surgeon immediately checked the location of the catheter. Digital subtraction angiography revealed that the hemodialysis cuff catheter had punctured the mediastinal area from the left brachiocephalic vein. The patient was diagnosed with left brachiocephalic vein perforation (d ≈ 5 mm). Fortunately, the brachiocephalic vein perforation was successfully repaired with two embolization microcoils after comprehensive assessment and multidisciplinary consultation.Conclusion: Brachiocephalic vein perforation can be repaired with embolization microcoils during hemodialysis catheter placement, and this method of interventional treatment is safe and effective.

COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.

ObjectiveTo evaluate the association between musculoskeletal pain and incident sarcopenia and further explore the mediating effect of depressive symptoms among middle-aged and older Chinese adults.MethodsUsing the data from the China Health and Retirement Longitudinal Study 2011 and 2015, we included 12,788 participants in the cross-sectional analysis and 8,322 for the longitudinal analysis. Musculoskeletal pains located in the neck, back, waist, shoulder, arm, wrist, leg, knee, and ankle were self-reported at baseline and follow-up. The diagnosis criteria of sarcopenia was based on the Asian Working Group for Sarcopenia 2019. Multivariable logistic regression models were used to evaluate the association between musculoskeletal pain, and the Karlson–Holm–Breen (KHB) method was used to explore the mediating effect of depressive symptoms.ResultsOver the 4-year follow-up, 445 participants were identified with incident sarcopenia. In the longitudinal analysis, participants with baseline musculoskeletal pain (adjusted odds ratio (OR): 1.37, 95% confidence interval (CI): 1.07–1.76), persistent musculoskeletal pain (OR:1.68, 95%CI: 1.28–2.24), and persistent waist pain (OR:1.46, 95%CI: 1.04–2.03) were significantly associated with increased the risk of incident sarcopenia. Furthermore, depressive symptoms were found to partially mediate the association between musculoskeletal pain and incident sarcopenia.ConclusionPersistent musculoskeletal pain, especially in waist area, was positively associated with a higher risk of sarcopenia among the middle-aged and older Chinese. Depressive symptoms played a partial mediating role in this association.

IntroductionAnal canal duplication (ACD) is a rare entity of gastrointestinal duplication that may be asymptomatic or present complications, such as abscess, fistulae, or malignant changes. The diagnosis and rational management of ACD still need to be clarified.Case presentationWe present a case of an 18-month-old girl with intractable perianal erosion and painful bowel movements for one year, and chronic constipation for six months. Fistulography revealed a tubular structure (3 cm in length), located posterior to the native anal canal. Mucosectomy was performed through a perineal approach combined with a coccigeal approach, and the postoperative course was uneventful. The pathological findings confirmed the diagnosis of ACD with heterotopic gastric mucosa, a rare combination that has not been described in the literature before. A literature search was conducted on the Medline database for studies reporting ACD in children. The study pool consisted of 77 cases of ACD from 32 studies, including the present case. According to our case report and in line with the literature, 43 cases (55.84%) were incidentally found; the most frequent symptom was constipation (14.29%), followed by painful anal mass or sacral pain (10.39%), and recurrent fistula (7.79%). Coexisting diseases were observed in 31 patients (40.26%), including 19 (24.68%) cases associated with presacral masses. Surgical management was employed in 73 patients (94.81%). ACD excision was performed in 47 patients (64.38%), combined with presacral mass resection or coccygectomy in 19 cases (26.03%).ConclusionPreoperative imaging, including fistulography, ultrasonography, and magnetic resonance imaging, can provide useful information, especially for screening its associated anomalies. To prevent potential complications, surgical removal of ACD and associated anomalies is recommended. Mucosectomy may be one of the most effective surgical options for ACD due to its excellent functional outcome.

Novel variant infectious bursal disease virus (nvIBDV) is an emerging genotype (A2dB1b) that can cause severe and prolonged immunosuppression in young chickens. Despite current commercial vaccines being proven to lack complete protection against nvIBDV, it remains unclear whether the oil emulsion inactivated vaccines (OEVs) of the homologous and heterologous virus or booster immunization can provide effective protection. In this study, OEVs with two types of nvIBDV isolates QZ191002 (A-nv/B-nv) and YL160304 (A-nv/B-HLJ0504-like) were prepared and evaluated the protective effects of OEVs plus the booster immunizations with different current commercial vaccines against the challenge of nvIBDVs. The results from vaccination-challenge experiments showed that nvIBDV could break through the protection provided by only one immunization dose of the commercial vaccines, with the protection rates ranging from 40% to 60%. Interestingly, even with booster immunization with different commercial vaccines, the protection rates could only be increased to 60%–80%. As expected, only the OEVs of the homologous virus could provide 100% protection against the homologous nvIBDV, which could induce high-level specific antibodies, ameliorate target organ damage, and significantly reduce the viral load of the bursal in the challenged chickens. Notably, YL160304-OEV performed better than QZ191002-OEV, providing 100% protection not only against the challenge of homologous strain but also against that of heterologous QZ191002 strain. Antibody levels of the immunized chickens gradually increased after a short decline and reached the highest level on the age of 28 days. Similarly, the percentages of lymphocytes CD4+, CD8+ T, and B in peripheral blood lymphocytes (PBLs) were significantly increased on 21 d and 28 d. Notably, despite the nvIBDV, OEVs initially induced a delayed responses in the early stages but ultimately reach higher levels of CD4+ and CD8+ T lymphocytes. The results of study suggest that even booster immunization with different commercial vaccines cannot provide complete protection against nvIBDV, while the OEVs made by the nvIBDVs can provide full protection. Moreover, YL160304-OEV exhibits a broader protective spectrum against different nvIBDV strains, making it a potential candidate for the development of new vaccine.

PurposeGynecologic oncology laparotomy leads to severe postoperative pain. We aimed to evaluate the effects of preemptive multimodal analgesic regimen on postoperative opioid consumption for patients undergoing gynecologic oncology laparotomy.MethodsIn this prospective, randomized clinical trial, 80 female patients scheduled for gynecologic oncology laparotomy were randomized to receive preemptive multimodal analgesia consisted of transversus abdominis plane (TAP) block, cyclooxygenase−2 inhibitors, acetaminophen and intravenous morphine patient-controlled analgesia (PCA) (Study group) or conventional analgesia with cyclooxygenase−2 inhibitors and morphine PCA (Control group). The primary outcome was morphine consumption in the first 24 h after surgery. Secondary outcomes were pain scores, nausea, vomiting, time to ambulation and flatus, length of hospital stay, satisfaction score, the 40-item Quality of Recovery score (QoR-40) and the Short-Form Health Survey (SF-36) scale.ResultsMorphine consumption in the first 24 h was 6 (3–9.8) mg in the Study group and 7 (3.5–12.5) mg in the Control group (p = 0.222). The Study group showed lower morphine consumption up to 6 h, lower pain scores up to 48 h, and earlier time to ambulation and flatus. The global QoR-40 score at 48 h [182 (173–195) vs. 173.5 (154–185.5), p = 0.024], subdimension scores of physical dependence at 24 h, physical comfort and pain at 48 h were significantly improved in the Study group.ConclusionPreemptive multimodal analgesia was not superior to conventional analgesia in reducing 24 h morphine consumption; however, it showed a significantly improved pain control and early quality of recovery thus can be recommended for gynecologic oncology patients undergoing laparotomy.

BackgroundTransmission-blocking vaccines (TBVs) can effectively prevent the community’s spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in P. vivax. Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite Plasmodium berghei and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in P. vivax.Methods and findingsThe full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the Escherichia coli expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the pvqsox gene into the P. berghei pbqsox gene knockout genome was developed to express full-length PvQSOX protein in P. berghei (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic P. berghei gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both in vivo and in vitro using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field P. vivax isolates (named isolates #1–4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the P.vivax Salvador (Sal) I strain sequences, the pvqsox in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution.ConclusionsOur results suggest that PvQSOX could serve as a potential P. vivax TBVs candidate, which warrants further evaluation and optimization.

The giant panda (Ailuropoda melanoleuca) is recognized worldwide as an icon for wildlife conservation. The Qinling subspecies (Ailuropoda melanoleuca qinlingensis) inhabiting the Qinling Mountains is more endangered. Previous studies have indicated that Qinling pandas are potentially at risk from environmental pollutants, which they are exposed to via food and drinking water. However, there is little information about the surface water quality in the Qinling Mountains, and it is unknown whether drinking water is an important pollutant source for pandas. Water samples were collected from five different nature reserves in Qinling, each of which is home to a population of pandas. The samples were analyzed for five essential metals of copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), and nickel (Ni) and four non-essential metals of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). The concentrations of all heavy metals (HMs) were higher in buffer zones than in the core areas and were highest in Foping and Niuweihe nature reserves. The concentrations of mercury exceeded the water quality standard in the core zone of three reserves, suggesting that NWH (Niuweihe), THS (Tianhuashan), and PHL (Pingheliang) giant panda populations were at risk from mercury toxicity. The accumulation of other elements over time could also pose a serious risk to pandas. Three main sources of pollution were identified: coal combustion, waste incineration, and fertilizer use; traffic-related activities; and metal mining. Environmental pollution is compromising the efforts to conserve the giant panda, and measures need to be put in place to control pollution sources.

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.

IntroductionMandible distraction osteogenesis (MDO) is widely used to reconstruct the mandible in patients with mild Hemifacial microsomia (HFM). However, the masseter's response to mandible distraction remains unclear.MethodsIn this study, we analyze the effect of the surgical intervention on masseter muscle by a retrospective analysis. The procedure consisted of a five-day latent period, a three-week distraction period, and a six-month consolidation period. CT data were manually segmented and measured with Mimics software before surgery, within 3 months, and more than 1 year postoperatively. Masseter volume, masseter length, masseter width, and mandible ramus height were measured and analyzed using paired t-test, Pearson, and Spearman correlation analysis.ResultsWe included 21 patients with HFM who underwent mandible distraction osteogenesis from 2015 to 2020. The masseter volume on the affected side increased immediately after surgery from (6,505.33 ± 3,671.95) mm3 to (10,194.60 ± 5638.79) mm3, but decreased to (8,148.38 ± 3,472.57) mm3 at the second follow-up correlated to mandible ramus height (r = 0.395, P = 0.038). A similar trend was observed in changes in masseter length. Symmetry and width of masseter muscle had no longitudinal statistical significance.DiscussionMasseter muscle involvement benefits from MDO in the short term. To achieve long-term efficacy, more attention should be paid to muscle reconstruction.

Background and objectiveThe rupture risk of intracranial aneurysms (IAs) is related to their arterial origin, but whether the different segments of the artery have different risks and act as independent risk factors is still unknown. Our study aimed to investigate the rupture risk of IAs in different arterial segments in a large Chinese cohort.MethodsImaging and clinical data of consecutive patients with IAs diagnosed by Computed Tomography angiography (CTA) from January 2013 to December 2022 were collected. Two neuroradiologists independently identified ruptured and unruptured IAs based on imaging and medical records. The internal carotid artery (ICA), middle cerebral artery (MCA), anterior cerebral artery (ACA), vertebral artery (VA), and posterior cerebral artery (PCA) were segmented according to the Bouthillier and Fischer segmentation methods. Stenoses of the proximal parent vessel were evaluated and documented. The Institutional Review Board (IRB) at Beijing Tiantan Hospital approved this retrospective study.ResultsA total of 3,837 aneurysms {median size 3.5 mm [interquartile range (IQR) 2.6–5.1 mm]; 532 ruptured} were included in this study from 2,968 patients [mean age: 57 years (IQR 50–64); male patients: 1,153]. Ruptured aneurysms were most commonly located in the posterior inferior cerebellar artery (PICA) (52.9%), anterior communicating artery (ACoA) (33.8%), other locations (33.3%), ACA (22.4%), and basilar artery (BA) (21.4%). The locations with the highest likelihood of rupture were the C7 ICA (21.3%), M2 MCA (24.0%), distal MCA (25.0%), and A2 ACA (28.1%). IAs originating from the C7 (p < 0.001), dM1 (p = 0.022), and dA1 (p = 0.021) segments were independent risk factors for rupture. IAs without stenosis of the proximal parent vessel were associated with a higher risk of rupture (p = 0.023).ConclusionThere are unique associations between the origins of aneurysms from various arterial segments. Aneurysms originating from the anterior communicating artery (ACoA), BA, PICA, A2, dA, C7, and M2 indicate a higher risk of rupture. Aneurysms originating from C4, C5, and C6 indicate a lower risk of rupture. C7 IAs, ACoA IAs, and PICA IAs seem to be independent risk factors.

IntroductionCiltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated improved efficacy vs. standard of care (SOC; daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with a ≥ complete response (≥CR) rate of 73.1% vs. 21.8%.MethodsA cost-per-responder model was developed to assess the value of cilta-cel and SOC (87% DPd and 13% PVd) based on the CARTITUDE-4 trial data from a US mixed payer perspective (76.7% commercial, 23.3% Medicare). The model was developed using progression-free survival (PFS), overall survival (OS), and ≥CR endpoints from CARTITUDE-4 over a period of 25.4 months. Inpatient stays, outpatient visits, drug acquisition, administration, and monitoring costs were included. The base-case model assumed an inpatient setting for each cilta-cel infusion; another scenario included 30% outpatient and 70% inpatient infusions. Costs of managing grade 3-4 adverse events (AEs) and grade 1-4 cytokine release syndrome and neurotoxicity were included. Subsequent therapy costs were incurred after disease progression; terminal care costs were considered upon death events. Outcomes included total cost per treated patient, total cost per complete responder, and cost per month in PFS between cilta-cel and SOC. Costs were adjusted to 2024 US dollars.ResultsTotal cost per treated patient, total cost per complete responder, and total cost per month in PFS were estimated at $704,641, $963,941, and $30,978 for cilta-cel, respectively, and $840,730, $3,856,559, and $42,520 for SOC over the 25.4-month period. Cost drivers included treatment acquisition costs before progression and subsequent treatment costs ($451,318 and $111,637 for cilta-cel; $529,795 and $265,167 for SOC). A scenario analysis in which 30% of patients received an outpatient infusion (assuming the same payer mix) showed a lower cost per complete responder for cilta-cel ($956,523) than those with an infusion in the inpatient setting exclusively.DiscussionThis analysis estimated that cost per treated patient, cost per complete responder, and cost per month in PFS for cilta-cel were remarkably lower than for DPd or PVd, highlighting the substantial clinical and economic benefit of cilta-cel for patients with RRMM.

IntroductionThe prevalence of male infertility has been increasing globally, necessitating the search for safe and nontoxic active compounds to alleviate reproductive dysfunction. Although the precise mechanism remains unknown, Cynomorium songaricum Rupr. (CS) extract has protective effects on the reproductive system. The effect of C. songaricum Rupr. flavonoids (CSF) on reproductive injury and testicular mesenchymal stem cell viability in male mice and TM3 cells was investigated.MethodsWe explored the possible association between these effects and the testosterone (T) synthesis pathway. Mice were administered cyclophosphamide to induce reproductive damage, followed by CSF administration. Body mass and organ index were recorded. Pathological changes in T and the epididymis were observed using hematoxylin-eosin staining. ELISA measured the serum levels of T, luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and estradiol (E2) in mice. Fructose and zinc ion levels in the seminal plasma were measured. TM3 cells were treated with Bisphenol A (BPA) and different concentrations of CSF, followed by proliferative evaluations using the CCK-8 assay and T and LH level assessments using ELISA. Furthermore, the expression of steroidogenic enzyme genes and proteins was investigated using western blotting and RT-PCR.ResultsCSF exhibited a notable reduction in reproductive damage and improved pathological changes in testicular and epididymal tissues. CSF group demonstrated substantially higher levels of seminal plasma fructose and zinc ions; markedly elevated serum levels of T, LH, GnRH, and FSH; and lower levels of E2 than those of the model group. Intracellular T content and secretion of T and LH increase with CSF while effectively mitigating BPA-induced damage to TM3 cells. CSF group exhibited substantially higher gene and protein expression of steroidogenic enzymes than those of the model group, both in vivo and in vitro. CSF ameliorates reproductive impairment by enhancing the expression of pivotal enzymes involved in synthesizing T.DiscussionCSF ameliorates cyclophosphamide-induced reproductive impairment and bisphenol A-induced TM3 cell damage in mice by regulating sex hormone levels in the Hypothalamic-Pituitary-Gonadal Axis (HPG axis) and upregulating the expression of steroidogenic enzymes. Therefore, CS is a potential treatment for male reproductive impairment.

ObjectiveIt has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement.Methods2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing.ResultsPatients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8.ConclusionThe early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.

IntroductionAssessing the influence of respiratory assistive devices on the diaphragm mobility is essential for advancing patient care and improving treatment outcomes. Existing respiratory assistive robots have not yet effectively assessed their impact on diaphragm mobility. In this study, we introduce for the first time a non-invasive, real-time clinically feasible ultrasound method to evaluate the impact of soft wearable robots on diaphragm displacement.MethodsWe measured and compared diaphragm displacement and lung volume in eight participants during both spontaneous and robotic-assisted respiration. Building on these measurements, we proposed a human-robot coupled two-compartment respiratory mechanics model that elucidates the underlying mechanism by which our extracorporeal wearable robots augments respiration. Specifically, the soft robot applies external compression to the abdominal wall muscles, inducing their inward movement, which consequently pushes the diaphragm upward and enhances respiratory function. Finally, we investigated the level and shape of various robotic assistive forces on diaphragm motion.ResultsThis robotic intervention leads to a significant increase in average diaphragm displacement by 1.95 times and in lung volume by 2.14 times compared to spontaneous respiration. Furthermore, the accuracy of the proposed respiratory mechanics model is confirmed by the experimental results, with less than 7% error in measurements of both diaphragm displacement and lung volume. Finally, the magnitude of robotic assistive forces positively correlates with diaphragm movement, while the shape of the forces shows no significant relationship with diaphragm activity.ConclusionOur experimental findings validate the effective assistance mechanism of the proposed robot, which enhances diaphragm mobility and assists in ventilation through extracorporeal robotic intervention. This robotic system can assist with ventilation while increasing diaphragm mobility, potentially resolving the issue of diaphragm atrophy. Additionally, this work paves the way for improved robotic designs and personalized assistance, tailored to the dynamics of the diaphragm in respiratory rehabilitation.

IntroductionAnalyzing the correlation between planktonic eukaryotic communities (PECs) and aquatic physicochemical parameters (APPs) provides important references for predicting the impact of climate change and human activities on aquatic ecosystems.MethodsTo assess the influence of seasons and APPs on PEC structures in lakes and rivers, we utilized high-throughput sequencing of the 18S rRNA gene to analyze PEC structures in a lake and seven rivers in the Chaohu Lake Basin and analyzed their correlations with APPs.ResultsOur results revealed that PEC structure was significantly affected by season, with the highest α-diversity observed in summer. Furthermore, we identified several APPs, including water temperature, conductivity, dissolved oxygen, pH, phosphate, total phosphorus, trophic level index (TLI), nitrate, ammonia nitrogen, and total nitrogen, that significantly influenced PEC structures. Specifically, we found that Stephanodiscus hantzschii, Simocephalus serrulatus, Cryptomonas sp. CCAC_0109, Pedospumella encystans, Actinochloris sphaerica, Chlamydomonas angulosa, Gonyostomum semen, Skeletonema potamos, Chlamydomonas klinobasis, Pedospumella sp., and Neochlorosarcina negevensis were significantly correlated to TLI, while Limnoithona tetraspina, Theileria sp., and Pseudophyllomitus vesiculosus were significantly correlated to the water quality index (WQI). However, our random forest regression analysis using the top 100 species was unable to accurately predict the WQI and TLI.DiscussionThese results provide valuable data for evaluating the impact of APPs on PEC and for protecting water resource in the Chaohu Lake Basin.

BackgroundTo meet the growing health needs of older people, the Chinese government has introduced internet-based home care services. However, most rural older people have not yet benefited from such services, and the willingness to use these services and the factors influencing them remain unclear.ObjectiveWe aim to investigate the current willingness of rural older people to use internet-based home care services and analyze the factors.MethodsWe conducted a cross-sectional study across multiple centers using general information and self-developed questionnaires. Qualitative interviews, a literature review and the Delphi method were employed to develop the questionnaire. A total score of the questionnaire above 78 or higher indicates a high willingness to use internet-based home care services. Descriptive statistics, t-tests, one-way ANOVA, and multiple linear regression were used to explore the factors that influence the willingness of rural older people to use internet-based home care services.ResultsWe surveyed 349 rural older people. The total score of rural older people’s willingness to use internet-based home care services was 84.49 ± 10.88, indicating high willingness, with the highest score for the dimension of perceived usefulness and lower scores for the dimension of perceived ease of use. Multiple linear regression analysis revealed that gender, education level, residence status, number of chronic diseases, and knowledge of internet-based home care services were the most important factors for rural older people (all p

Nicosulfuron, a widely utilized herbicide, is detrimental to some maize varieties due to their sensitivity. Developing tolerant varieties with resistance genes is an economical and effective way to alleviate phytotoxicity. In this study, map-based cloning revealed that the maize resistance gene to nicosulfuron is Zm00001eb214410 (CYP81A9), which encodes a cytochrome P450 monooxygenase. qRT- PCR results showed that CYP81A9 expression in the susceptible line JS188 was significantly reduced compared to the resistant line B73 during 0-192 hours following 80 mg/L nicosulfuron spraying. Meanwhile, a CYP81A9 overexpression line exhibited normal growth under a 20-fold nicosulfuron concentration (1600 mg/L), while the transgenic acceptor background material Zong31 did not survive. Correspondingly, silencing CYP81A9 through CRISPR/Cas9 mutagenesis and premature transcription termination mutant EMS4-06e182 resulted in the loss of nicosulfuron resistance in maize. Acetolactate Synthase (ALS), the target enzyme of nicosulfuron, exhibited significantly reduced activity in the roots, stems, and leaves of susceptible maize post-nicosulfuron spraying. The CYP81A9 expression in the susceptible material was positively correlated with ALS activity in vivo. Therefore, this study identified CYP81A9 as the key gene regulating nicosulfuron resistance in maize and discovered three distinct haplotypes of CYP81A9, thereby laying a solid foundation for further exploration of the underlying resistance mechanisms.

BackgroundThis study aimed to identify the predictive factors for prolonged length of stay (LOS) in elderly type 2 diabetes mellitus (T2DM) patients suffering from cerebral infarction (CI) and construct a predictive model to effectively utilize hospital resources.MethodsClinical data were retrospectively collected from T2DM patients suffering from CI aged ≥65 years who were admitted to five tertiary hospitals in Southwest China. The least absolute shrinkage and selection operator (LASSO) regression model and multivariable logistic regression analysis were conducted to identify the independent predictors of prolonged LOS. A nomogram was constructed to visualize the model. The discrimination, calibration, and clinical practicality of the model were evaluated according to the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsA total of 13,361 patients were included, comprising 6,023, 2,582, and 4,756 patients in the training, internal validation, and external validation sets, respectively. The results revealed that the ACCI score, OP, PI, analgesics use, antibiotics use, psychotropic drug use, insurance type, and ALB were independent predictors for prolonged LOS. The eight-predictor LASSO logistic regression displayed high prediction ability, with an AUROC of 0.725 (95% confidence interval [CI]: 0.710–0.739), a sensitivity of 0.662 (95% CI: 0.639–0.686), and a specificity of 0.675 (95% CI: 0.661–0.689). The calibration curve (bootstraps = 1,000) showed good calibration. In addition, the DCA and CIC also indicated good clinical practicality. An operation interface on a web page (https://xxmyyz.shinyapps.io/prolonged_los1/) was also established to facilitate clinical use.ConclusionThe developed model can predict the risk of prolonged LOS in elderly T2DM patients diagnosed with CI, enabling clinicians to optimize bed management.

IntroductionType 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS.MethodsThe gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein–protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor–mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed.ResultsA total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein–protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis.DiscussionIn this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.

BackgroundAn accumulating body of research indicates that the pons is related to the occurrence of depression. Si-Ni-San (SNS) is a well-known Chinese herbal formula that is used to treat depression. Chinese herbal formulae have multiple therapeutic characteristics. Although it has been proven that SNS can exert antidepressant effects by improving changes in the limbic system, it is currently unclear whether SNS has therapeutic targets in the pons. This study aimed to explore the therapeutic targets of SNS in the pons for depression treatment.Materials and methodsTwo experiments were conducted. In Experiment 1, 32 rats were divided into four groups: (1) a Control (C) group that received distilled water as a vehicle; (2) a Model (M) group that received the chronic unpredictable mild stress (CUMS) procedure and was administered distilled water; (3) a Stress + SNS (MS) group that received the CUMS procedure and was administered SNS dissolved in distilled water; and (4) a Stress + Fluoxetine (MF) group that received the CUMS procedure and was administered fluoxetine dissolved in distilled water. The open field test (OFT), the sucrose preference test (SPT), and the novel object recognition test (NOR) were performed to test the antidepressant effects of SNS. High-throughput mRNA sequencing (RNA-seq) was used to explore possible gene targets of SNS in the pons, and quantitative real-time PCR was performed to verify the results. High-performance liquid chromatography was used to detect neurotransmitters. Finally, correlation analyses were conducted between behaviors, genes expression, and neurotransmitters. In Experiment 2, 18 rats were divided into the same three groups as in Experiment 1: (1) C, (2) M, and (3) MS. fMRI was used to confirm whether SNS altered the pons in a rat model of depression.ResultsSNS significantly improved sucrose preference in the SPT and TN-TO in the NOR compared to the M group (P < 0.05). RNA-seq filtered 49 differentially expressed genes(DEGs) that SNS could reverse in the pons of the CUMS depression model. Real-time PCR detected six genes, including Complexin2 (Cplx2), Serpinf1, Neuregulin1 (Nrg1), Annexin A1 (Anxa1), β-arrestin 1 (Arrb1) and presenilin 1 (Psen1). SNS significantly reversed changes in the expression of Anxa1, Nrg1, and Psen1 caused by CUMS (P < 0.05), which is consistent with the DEGs results. Additionally, SNS significantly reversed norepinephrine (NE) changes in the pons. There were 18 noteworthy correlations between behavior, genes, and neurotransmitters (P < 0.05). fMRI showed that SNS can decrease the amplitude of low-frequency fluctuations (ALFF) in the pons of living depressed rats.ConclusionThe pons is an important target brain region for SNS to exert its antidepressant effects. SNS may improve pontine NE levels by regulating the Anxa1, Nrg1, and Psen1 genes, thereby exerting antidepressant effects and improving cognitive function.

The Maoping superlarge germanium-rich lead–zinc deposit is a typical nonmagmatic hydrothermal deposit that is structurally controlled in the Sichuan–Yunnan–Guizhou lead–zinc polymetallic metallogenic area. The orebodies are distributed in several formations. This paper is based on large-scale alteration mapping combined with porosity and permeability measurements. We delineated the mineralization–alteration zones of different ore-bearing formations, explored the geological significance of porosity and permeability, and proposed prospecting directions. The research results indicate that during the mineralization period, the ore-forming metal fluids migrated from the deep part of the SSW region to the shallow part of the NNE region along the ore-guiding structure (Maoping Fault). Through the ore distribution structure, depressurization boiling occurred in the open space of the NE-trending interlayered sinistral compressive–torsional faults in several ore-bearing formations, resulting in fluid precipitation and the formation of different brecciated hot-melt dolomite lead–zinc mineralization zones. From the orebody to the wallrock, the C2w Formation and D3zg Formation are divided into four different mineralization–alteration zones. Tectonic activity affects the properties, migration, and precipitation of fluids, thereby controlling the alteration characteristics generated during fluid migration and thus changing the porosity and permeability. The porosity and permeability of strata on the NW flank of the anticline are greater than those of strata on the SE flank. On the NW flank, the greater the degree of mineralization–alteration is, the greater the porosity and permeability are, and the porosity of the orebody is lower than that during dolomitization. Finally, we believe that the NW flank of the anticline is an important area for prospecting. The pyrite + striped altered dolomite zone (Zones II–III) in the C2w limestone and the pyrite + strong dolomite zone (Zones II–III) in the D3zg dolomite are important prospecting indicators.

PurposeSmall dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design.MethodsWe identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis.ResultsIn univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117–1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106–1.597, P = 0.002).ConclusionsFindings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.

Background: Wuwei Xiaodu Drink (WWXDD), a classical decoction of traditional Chinese medicine, has been clinically used for the treatment of gout in China for many years. This study aimed to demonstrate the efficacy of WWXDD in treating gout flares and elucidate its underlying therapeutic mechanism.Methods: A randomized control trial was conducted to compare the effectiveness of WWXDD with low-dose colchicine in gout arthritis. The primary outcome was the clinical response rate on the 7th day, and joint syndrome score and serological tests were secondary outcome measures and were compared in the two groups on the 1st and 7th day. Then we used a network pharmacology approach to investigate the possible mechanism of WWXDD in treating gout, and the effects of WWXDD on the MSU-induced rat model were observed.Results: In the clinical trial, a total of 78 participants completed the study, and the results demonstrated comparable clinical complete response rates, joint symptom scores, and serological test outcomes between the two groups on the 7th day. Network pharmacology analysis identified 51 core genes that target gout and WWXDD interactions. Notably, strong significant correlations were observed with inflammation cytokine genes and metabolism-related genes. Furthermore, it was found that WWXDD reduced gene expression levels of inflammation cytokines including IL-1β, TNF, and IL-18 in an MSU-induced rat model while increasing IL-10 expression. Additionally, WWXDD decreased insulin gene expression in this model. Moreover, WWXDD exhibited a reduction in both gene and protein expressions associated with the NLRP3-mediated inflammatory pathway in inflamed joints of rats.Conclusion: The results of the present study suggested the anti-inflammatory effects of WWXDD in the treatment of gouty arthritis, partially through inhibiting NLRP3 inflammasome activation.Clinical Trial Registration:ClinicalTrials.gov, identifier ChiCTR2100047807.

Introduction: Research on Glycyrrhiza uralensis, a nonhalophyte that thrives in saline–alkaline soil and a traditional Chinese medicinal component, is focused on improving its ability to tolerate salt stress to increase its productivity and preserve its “Dao-di” characteristics. Furthermore, the inoculation of bioagents such as Bacillus subtilis to increase plant responses to abiotic stressors is currently a mainstream strategy. Mitogen-activated protein kinase (MAPK), a highly conserved protein kinase, plays a significant role in plant responses to various abiotic stress pathways.Methods: This investigation involved the identification of 21 members of the GuMAPK family from the genome of G. uralensis, with an analysis of their protein conserved domains, gene structures, evolutionary relationships, and phosphorylation sites using bioinformatics tools.Results: Systematic evolutionary analysis of the 21 GuMAPKs classified them into four distinct subgroups, revealing significant differences in gene structure and exon numbers. Collinearity analysis highlighted the crucial role of segmental duplication in expanding the GuMAPK gene family, which is particularly evident in G. uralensis and shows a close phylogenetic relationship with Arabidopsis thaliana, tomato, and cucumber. Additionally, the identification of phosphorylation sites suggests a strong correlation between GuMAPK and various physiological processes, including hormonal responses, stress resistance, and growth and development. Protein interaction analysis further supported the role of GuMAPK proteins in regulating essential downstream genes. Through examination of transcriptome expression patterns, GuMAPK16-2 emerged as a prospective pivotal regulatory factor in the context of salt stress and B. subtilis inoculation, a finding supported by its subcellular localization within the nucleus.Discussion: These discoveries offer compelling evidence for the involvement of GuMAPK in the salt stress response and for the exploration of the mechanisms underlying B. subtilis’ enhancement of salt tolerance in G. uralensis.

BackgroundIncreasing evidence reveals the involvement of mitochondria and macrophage polarisation in tumourigenesis and progression. This study aimed to establish mitochondria and macrophage polarisation-associated molecular signatures to predict prognosis in gastric cancer (GC) by single-cell and transcriptional data.MethodsInitially, candidate genes associated with mitochondria and macrophage polarisation were identified by differential expression analysis and weighted gene co-expression network analysis. Subsequently, candidate genes were incorporated in univariateCox analysis and LASSO to acquire prognostic genes in GC, and risk model was created. Furthermore, independent prognostic indicators were screened by combining risk score with clinical characteristics, and a nomogram was created to forecast survival in GC patients. Further, in single-cell data analysis, cell clusters and cell subpopulations were yielded, followed by the completion of pseudo-time analysis. Furthermore, a more comprehensive immunological analysis was executed to uncover the relationship between GC and immunological characteristics. Ultimately, expression level of prognostic genes was validated through public datasets and qRT-PCR.ResultsA risk model including six prognostic genes (GPX3, GJA1, VCAN, RGS2, LOX, and CTHRC1) associated with mitochondria and macrophage polarisation was developed, which was efficient in forecasting the survival of GC patients. The GC patients were categorized into high-/low-risk subgroups in accordance with median risk score, with the high-risk subgroup having lower survival rates. Afterwards, a nomogram incorporating risk score and age was generated, and it had significant predictive value for predicting GC survival with higher predictive accuracy than risk model. Immunological analyses revealed showed higher levels of M2 macrophage infiltration in high-risk subgroup and the strongest positive correlation between risk score and M2 macrophages. Besides, further analyses demonstrated a better outcome for immunotherapy in low-risk patients. In single-cell and pseudo-time analyses, stromal cells were identified as key cells, and a relatively complete developmental trajectory existed for stromal C1 in three subclasses. Ultimately, expression analysis revealed that the expression trend of RGS2, GJA1, GPX3, and VCAN was consistent with the results of the TCGA-GC dataset.ConclusionOur findings demonstrated that a novel prognostic model constructed in accordance with six prognostic genes might facilitate the improvement of personalised prognosis and treatment of GC patients.

BackgroundStatins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy.MethodsA quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the “Up to standard” (US) group and the “Below standard” (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites.ResultsA total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism.ConclusionsThe findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

The field of emergency risk management in chemical parks has been characterized by a lack of fast, precise and dynamic prediction methods. The application of computational fluid dynamics (CFD) models, which offer the potential for dynamic and precise prediction, has been hindered by high computational costs. Therefore, taking liquid benzene as a case study, this paper combined machine learning (ML) algorithms with a CFD-based precise prediction model, to develop an ML model for fast dynamic prediction of heavy gas leakage consequences in chemical parks. Employing the CFD data as the input, the prediction models were developed using ML algorithms, refined with Bayesian optimization for parameter tuning. This study utilized PHOENICS software to establish a dynamic prediction model for the diffusion of liquid benzene leakage, validated by Burro nine experiment data. Comparative analyses of models based on five ML algorithms were conducted to evaluate the reliability of their predictions using both CFD standard and noisy data. The results indicated that temperature had the most significant effect on the consequences of the leakage accidents among four key factors (wind speed, temperature, leakage aperture and atmospheric stability), followed by wind speed. These factors served as input variables for ML model training. Among the models evaluated, the eXtreme Gradient Boosting (XGBoost) model showed superior performance, irrespective of the presence of noise in the data. An XGBoost-based fast prediction model was ultimately developed for predicting the consequences of liquid benzene leakage. A case analysis was conducted to validate the feasibility of the model prediction. The relative errors between the predicted and actual values of the model for acute exposure guideline level-1 (AEGL-1), AEGL-2, and AEGL-3 distances were 2.70%, 2.58%, and 0.23%, respectively. Furthermore, the XGBoost model completed the prediction in only 0.218 s, a stark contrast to the hours necessitated by the CFD model, thus offering substantial computational time savings while maintaining high accuracy levels. This paper introduces an ML model for fast dynamic prediction of heavy gas leakage, enabling chemical parks to make more timely and accurate decisions in emergency risk management.

The large-scale integration of renewable energy sources and power electronic devices has led to increasingly dispersed and networked characteristics of power quality disturbances in distribution systems. Traditional control devices, limited by their fixed-point control, no longer meet the development needs of modern distribution systems. Considering the distribution and structural characteristics of the current new-type sources and loads, a multifunctional inverter power quality coordinated control strategy based on comprehensive evaluation is proposed. This strategy aims to achieve power quality coordinated control by utilizing optimal compensation capacity while the grid-connected inverter provides active power output. Firstly, the traditional ipiq power quality detection method is analyzed and improved to enable detection of harmonics, reactive power, and three-phase imbalance currents in single-phase systems or three-phase four-wire systems. Secondly, in the power quality assessment, a balanced algorithm is employed to obtain the comprehensive evaluation index of power quality, thereby improving the deficiencies of single-weight evaluation. Next, to ensure the grid-connected inverter achieves optimal power quality coordinated control with minimal compensation capacity, an optimization compensation function is established between compensation capacity and comprehensive power quality index. This function is optimized using non-dominated sorting genetic algorithm to enhance equipment utilization and system economy. Finally, the feasibility and effectiveness of the proposed method are validated through simulations, demonstrating the achievement of optimal capacity configuration for power quality coordinated control while ensuring active power output by the grid-connected inverter.

IntroductionSiraitia grosvenorii (Swingle) C. Jeffrey, is an edible and traditional medicine widely used in China. Mogroside V (MGV) and mogrol (MG) are its main active ingredients, which have been found to be effective in the treatment of neurodegenerative diseases recently. However, whether they can effectively treat Parkinson’s disease (PD) and their underlying mechanisms have not been sufficiently explored. In this study, we investigated the neuroprotective and metabolic regulatory effects of MGV and MG on PD.Materials and methodsUsing SH-SY5Y cell models and an MPTP-induced mouse model of PD, we evaluated the compounds’ efficacy in mitigating MPP+-induced neurotoxicity and ameliorating motor deficits and dopaminergic neuron loss. Employing widely targeted metabolomics and bioinformatics analysis to investigate the Metabolic imbalance rectification caused by MGV and MG treatment. The vivo experimental protocol encompassed a 14-day drug administration regimen with mice randomly allocated into six groups (n = 9) receiving distinct compound dosages including a control group, a model group, MGV-H (30 mg/kg/day), MGV-L (10 mg/kg/day), MG-H (15 mg/kg/day), and MG-L (3 mg/kg/day).ResultsOur findings revealed that pre-treatment with MGV and MG significantly enhanced cell viability in SH-SY5Y cells exposed to MPP+, demonstrating a potent protective effect against neurotoxicity. In the MPTP mouse model, MGV-H, MGV-L, and MG-H significantly enhanced motor coordination as assessed by the rotarod test (p < 0.05); MGV-L and MG-H evidently inhibited dopaminergic neuronal loss in the substantia nigra pars compacta (p < 0.05). Furthermore, metabolomic analysis of the substantia nigra highlighted the restoration of metabolic balance, with MGV-L and MG-H impacting 160 differential metabolites and modulating key pathways disrupted in PD, including sphingolipid metabolism, fatty acid metabolism, and amino acid metabolism. Notably, treatment with MGV-L and MG-H led to the regulation of 106 metabolites, showing a recovery trend towards normal levels, which constitutes approximately 17.5% of the identified metabolites. Key metabolites such as n-acetyl-l-glutamate, hexadecanoic acid, and 9-octadecenal were significantly altered (p < 0.05), underscoring their broad-spectrum metabolic regulatory capacity.ConclusionThis study underscores the potential of natural compounds in developing comprehensive treatment strategies for neurodegenerative diseases, paving the way for future clinical research to validate the therapeutic efficacy of mogrosides in PD.

IntroductionHow to scientifically assess the health status of cities and effectively assist in formulating policies and planning for health city development remains a profound challenge in building a global “health community.”MethodsThis study employs the Building Research Establishment’s International Healthy Cities Index (BRE HCI), encompassing ten environmental categories and fifty-eight indicators, to guide and support the scientific development of healthy cities. The entropy weight-TOPSIS method and the rank sum ratio (RSR) method were applied to comprehensively rank and categorize the health development levels of fifteen global cities. Furthermore, through cluster analysis, this research identifies universal and unique indicators that influence the development of healthy cities.ResultsThe results indicate that: (1) Within the scope of 58 evaluation indicators, the precedence in weight allocation is accorded to the kilometres of bicycle paths and lanes per 100,000 population (0.068), succeeded by m2 of public indoor recreation space per capita (0.047), and kilometres of bicycle paths and lanes per 100,000 population (0.042). (2) Among the ten environmental categories, the top three in terms of weight ranking are transport (0.239), leisure and recreation (0.172), and resilience (0.125). Significant disparities exist between different cities and environmental categories, with the issue of uneven health development within cities being particularly prominent. (3) The study categorizes the development levels of healthy cities into three tiers based on composite scores: it classifies Singapore, Shanghai, and Amsterdam at an excellent level; places Dubai and Johannesburg at a comparatively poor level; and situates the remaining ten cities at a moderate level. (4) The analysis identifies 53 international common indicators and 5 characteristic indicators from the 58 indicators based on the significance of the clustering analysis (p < 0.05).DiscussionThe study proposes four strategic recommendations based on these findings: establishing a comprehensive policy assurance system, refining urban spatial planning, expanding avenues for multi-party participation, and augmenting distinctive health indicators. These measures aim to narrow the developmental disparities between cities and contribute to healthy global cities’ balanced and sustainable growth. However, due to existing limitations in sample selection, research methodology application, and the control of potential confounding variables, further in-depth studies are required in the future.

ObjectiveThe purpose of this study is to investigate potential associations between osteopenia, osteosarcopenia, and postoperative outcomes in patients with hepatobiliary-pancreatic cancer (HBPC).MethodsThree online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between osteopenia, osteosarcopenia, and outcomes of surgical treatment of HBPC patients from the start of each database to September 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies.ResultsThis analysis included a total of 16 articles with a combined patient cohort of 2,599 individuals. The results demonstrated that HBPC patients with osteopenia had significantly inferior OS (HR: 2.27, 95% CI: 1.70-3.03, p < 0.001) and RFS (HR: 1.96, 95% CI: 1.42-2.71, p < 0.001) compared to those without osteopenia. Subgroup analysis demonstrated that these findings were consistent across univariate and multivariate analyses, as well as hepatocellular carcinoma, biliary tract cancer, and pancreatic cancer. The risk of postoperative major complications was significantly higher in patients with osteopenia compared to those without osteopenia (OR: 1.66, 95% CI: 1.19-2.33, p < 0.001). Besides, we also found that the presence of osteosarcopenia in HBPC patients was significantly related to poorer OS (HR: 3.31, 95% CI: 2.00-5.48, p < 0.001) and PFS (HR: 2.50, 95% CI: 1.62-3.84, p < 0.001) in comparison to those without osteosarcopenia.ConclusionPreoperative osteopenia and osteosarcopenia can predict poorer OS and RFS with HBPC after surgery.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers in bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be a disease-modifying agent in the treatment of AD. Lithium’s neuroprotective properties in AD by acting on multiple neuropathological targets, such as reducing amyloid deposition and tau phosphorylation, enhancing autophagy, neurogenesis, and synaptic plasticity, regulating cholinergic and glucose metabolism, inhibiting neuroinflammation, oxidative stress, and apoptosis, while preserving mitochondrial function. Clinical trials have demonstrated that lithium therapy can improve cognitive function in patients with AD. In particular, meta-analyses have shown that lithium may be a more effective and safer treatment than the recently FDA-approved aducanumab for improving cognitive function in patients with AD. The affordability and therapeutic efficacy of lithium have prompted a reassessment of its use. However, the use of lithium may lead to potential side effects and safety issues, which may limit its clinical application. Currently, several new lithium formulations are undergoing clinical trials to improve safety and efficacy. This review focuses on lithium’s mechanism of action in treating AD, highlighting the latest advances in preclinical studies and clinical trials. It also explores the side effects of lithium therapy and coping strategies, offering a potential therapeutic strategy for patients with AD.

The evolutionary analysis showed that the GF14 family was conserved, however, there was limited evidence linking GF14s to plant height. In our investigations, we discovered a co-expression relationship between ZmGF14s and functionally characterized genes linked to plant height. In the co-expression network, we identified ZmGF14-3, a gene expression exhibiting a positive correlation with plant height in three maize varieties, we postulated that this gene could be intimately linked to plant height development. Subsequently, we cloned ZmGF14-3 from the maize B73 inbred line and overexpressed it in Arabidopsis, resulting in markedly dwarfed transgenic phenotypes. Measurements of endogenous phytohormones disclosed a significant reduction in concentrations of Gibberellic Acid 7 (GA7) and Indole-3-Acetic Acid (IAA) in the overexpressed Arabidopsis, furthermore, qPCR results highlighted a pronounced decrease in the expression levels of plant height-related genes when compared to the wild type, therefore, it is plausible to posit that ZmGF14-3 plays a pivotal role in regulating the growth and development of maize through interactions with various phytohormone-related genes. Thus, delving into the potential interactions between ZmGF14-3 and these genes holds the promise of yielding valuable insights into the molecular mechanisms underpinning plant height development in maize.

IntroductionThe outbreak of the COVID-19 pandemic has disrupted people’s routine, bringing uncertainty and stress, leading to mental health issues. This situation is particularly acute among Chinese prospective graduates in higher education stage as they cannot predict the outcomes of their studies, graduation, and career development, and therefore experience career-related stress.MethodsThis study included 4041 prospective graduates in higher education stage (using handy sampling) recruited in March 2020 as participants (MAge = 22.56, SD = 1.865), utilizing a Sparse Gaussian Graphical Model for regularized partial correlation network analysis of depression symptoms (by PHQ-9), anxiety symptoms (by GAD-7), and career-related stress, which aims to explore the role of career-related stress in the symptom networks of depression and anxiety among prospective graduates in their final semester.ResultsThe results revealed that fatigue, sad mood, and psychomotor symptoms in depression, as well as uncontrollable worry and trouble relaxing in anxiety, were central symptoms in the network. Additionally, sad mood and guilt belonging to depressive symptoms, and feeling afraid, restlessness, and irritability belonging to anxiety symptoms, served as bridge symptoms connecting symptom communities. Specifically, guilt as a depressive symptom showed a strong association with employment stress in career-related stress. There were no significant differences in network structure and global strength based on participants’ gender. However, despite no significant differences in network structure, the global strength of prospective graduates from Wuhan was significantly lower than samples from non-Hubei provinces, possibly indicative of a Typhoon Eye Effect.DiscussionThe findings of this study can inspire psychological professionals in higher education institutions to provide support for mental interventions and therapies for prospective graduates, and addressing career development issues.

The eastern Ordos Basin plays an important role in China’s coalbed methane (CBM) industry, boasting considerable CBM resources and pronounced reservoir heterogeneity, making it an ideal site for comparative research on deep and shallow CBM geology. In order to dissect the fundamental reasons for significant differences in production capacity between blocks and promote mutual learning from successful development experiences, this paper conducts a systematical study on the distribution characteristics of in-situ geological conditions of CBM reservoirs based on extensive well-testing data. Additionally, through coal permeability sensitivity experiments on coal samples with various Ro,max values, burial depths, and initial permeabilities, this study explores the change law of permeability during the process of CBM extraction. The results indicate that as the burial depth of coal seam increases, so do the temperature, pressure, and stress. Moreover, the distribution of geothermal gradient, reservoir pressure gradient, horizontal stress gradient, and lateral pressure coefficient tends to converge with increasing burial depth, with a turning depth typically between 1,000 and 1,500 m. Coal seams below 1,500 m generally exhibit a normal-fault type stress field with normal-overpressure. In-situ permeability decreases with depth, but the permeability in deep stress relief zones can be maintained at a relatively high level. A lower initial permeability corresponds to a smaller stress sensitivity coefficient and reduced temperature sensitivity effects, resulting in slower permeability damage during CBM extraction. However, when the reservoir pressure drops to depletion pressure, the maximum damage rate of permeability increases significantly, underscoring the importance of reservoir reconstruction in deep CBM development. This study provides a theoretical basis for selecting favorable areas for CBM exploration and development, as well as for designing efficient development plans in practice.

ObjectivesTo explore the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on lung adenosquamous cell carcinoma (ASC) with EGFR mutation.MethodsEfficacy of EGFR-TKIs in the treatment of advanced or recurrent lung ASC with EGFR mutations was assessed retrospectively in 44 patients. Pooled analysis of 74 patients using EGFR-TKIs, including 30 patients selected from 11 publications, was conducted.ResultsIn our retrospective research, patients treated with EGFR-TKI in ASC with EGFR mutations had objective response rate (ORR) of 54.5%, disease control rate (DCR) of 79.5%, median progression free survival (mPFS) of 8.8 months, and median overall survival (mOS) of 19.43 months, respectively. A pooled analysis reveals ORR, DCR, mPFS, and mOS are, respectively, 63.4%, 85.9%, 10.00 months, and 21.37 months for ASC patients. In patients with deletions in exon 19 and exon 21 L858R mutations, mPFS (11.0 versus 10.0 months, P=0.771) and mOS (23.67 versus 20.33 months, P=0.973) were similar. Erlotinib or gefitinib-treated patients had an overall survival trend that was superior to that of icotinib-treated patients.ConclusionsASC harboring EGFR mutations can be treated with EGFR-TKI in a similar manner to Adenocarcinoma (ADC) harboring EGFR mutations. There is still a need for further investigation to identify the separate roles of ASC’s two components in treating EGFR.

IntroductionSleep disorders are common in children with autism spectrum disorder (ASD). Transcranial magnetic stimulation (TMS) can influence the excitability of neuronal cells in stimulated areas, leading to improvements in sleep and other autistic symptoms. However, studies on clinical mechanisms of TMS in treating sleep disorders associated with ASD are limited. Therefore, we aimed to explore the effects of TMS on sleep structure and quality in children with ASD.MethodsBetween January 2020 and December 2021, recruitment was advertised through child and adolescent outpatient clinics and online platforms by the Hangzhou Seventh People’s Hospital and Lishui Second People’s Hospital. Sixty children with ASD who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were selected and randomly divided into the active TMS and sham TMS treatment groups. Thirty healthy children of the same age were recruited as controls. The active TMS group received bilateral low-frequency (0.5 Hz) TMS targeting the dorsolateral prefrontal cortex on both sides in children with ASD, whereas the sham TMS group received sham stimulation with the same stimulation time and location as the experimental group. Both groups were treated for 6 weeks, and the participants were assessed using the Sleep Disturbance Scale for Children (SDSC) before treatment, at 3 weeks, and at 6 weeks of intervention. Independent sample t-tests and difference t-tests were used for statistical analysis of the data.ResultsNo significant differences were observed in general demographic variables, such as age and sex, between the ASD and control groups (P>0.05). Independent sample t-test analysis showed that the total SDSC score, difficulty falling asleep, sleep maintenance, awakening disorders, sleep-wake transition disorders, excessive daytime sleepiness, and nocturnal hyperhidrosis scores were significantly higher in the ASD group than in the control group (P0.05). After 15 and 30 treatment sessions, the total SDSC score, difficulty falling asleep, sleep maintenance, sleep-wake transition disorders, and excessive daytime sleepiness scores were significantly higher in the sham TMS group than in the active TMS group (P

Both acute and chronic tendon injuries are the most frequently occurring musculoskeletal diseases in human and veterinary medicine, with a limited repertoire of successful and evidenced-based therapeutic strategies. Inflammation has been suggested as a key driver for the formation of scar and adhesion tissue following tendon acute injury, as well as pathological alternations of degenerative tendinopathy. However, prior efforts to completely block this inflammatory process have yet to be largely successful. Recent investigations have indicated that a more precise targeted approach for modulating inflammation is critical to improve outcomes. The nuclear factor-kappaB (NF-κB) is a typical proinflammatory signal transduction pathway identified as a key factor leading to tendon disorders. Therefore, a comprehensive understanding of the mechanism or regulation of NF-κB in tendon disorders will aid in developing targeted therapeutic strategies for human and veterinary tendon disorders. In this review, we discuss what is currently known about molecular components and structures of basal NF-κB proteins and two activation pathways: the canonical activation pathway and the non-canonical activation pathway. Furthermore, we summarize the underlying mechanisms of the NF-κB signaling pathway in fibrosis and adhesion after acute tendon injury, as well as pathological changes of degenerative tendinopathy in all species and highlight the effect of targeting this signaling pathway in tendon disorders. However, to gain a comprehensive understanding of its mechanisms underlying tendon disorders, further investigations are required. In the future, extensive scientific examinations are warranted to full characterize the NF-κB, the exact mechanisms of action, and translate findings into clinical human and veterinary practice.

Nasopharyngeal carcinoma with bone marrow metastasis presents a rare and challenging clinical scenario associated with exceedingly poor prognosis. While standard treatment regimens offer limited efficacy and tolerability in such cases, individualized approaches are increasingly necessary. We present the case of a 64-year-old male diagnosed with recurrent nonkeratinizing undifferentiated nasopharyngeal carcinoma with extensive bone marrow metastasis (rTxN0M1). Treatment was initiated with immunotherapy-based combination therapy, consisting of pembrolizumab and low-dose cisplatin, which resulted in an initial response. Subsequently, there was a transition to standard-dose nab-paclitaxel-cisplatin chemotherapy in combination with pembrolizumab, followed by maintenance therapy with pembrolizumab plus fruquintinib. The patient achieved a sustained response with renormalization of tumor markers, imaging findings, and bone biopsies, resulting in complete remission. This case highlights the successful management of nasopharyngeal carcinoma with extensive bone marrow metastasis through an individualized treatment approach incorporating immunotherapy.