Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Correlation analysis of whole genome sequencing of a pathogenic Escherichia coli strain of Inner Mongolian origin.

Anal swabs of 1-month-old Holstein calves with diarrhea were collected from an intensive cattle farm, and a highly pathogenic Escherichia coli strain was obtained by isolation and purification. To study the virulence and resistance genes of pathogenic E. coli that cause diarrhea in calves, a strain of E. coli E12 isolated from calf diarrhea samples was used as experimental material in this experiment, and the virulence of the E12 strain were identified by the mouse infection test, and the whole genome map of the E12 strain were obtained by whole-genome sequencing and analyzed for genome characterization. The results showed that the lethality of strain E12 was 100%, the total length of E12-encoded genes was 4,294,530 bp, Cluster of Orthologous Groups of proteins (COG) annotated to 4,194 functional genes, and the virulence genes of sequenced strain E12 were compared with the virulence genes of sequenced strain E12 from the Virulence Factors of Pathogenic Bacteria (VFDB), which contained a total of 366 virulence genes in sequenced strain E12. The analysis of virulence genes of E12 revealed a total of 52 virulence genes in the iron transferrin system, 56 virulence genes in the secretory system, 41 virulence genes in bacterial toxins, and a total of 217 virulence genes in the Adhesin and Invasins group. The antibiotic resistance genes of sequenced strain E12 were identified through the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Research Database, and it was found that its chromosome and plasmid included a total of 127 antibiotic resistance genes in four classes, and that E12 carried 71 genes related to the antibiotic efflux pumps, 36 genes related to antibiotic inactivation, and 14 antibiotic target alteration and reduced penetration into antibiotics, and 6 antibiotic resistance genes, and the resistance phenotypes were consistent with the genotypes. The pathogenic E. coli that causes diarrhea in calves on this ranch contains a large number of virulence and resistance genes. The results provide a theoretical basis for the prevention and treatment of diarrhea and other diseases caused by E. coli disease.

Efficacy and Safety of Remimazolam Versus Etomidate for Induction of General Anesthesia: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are "randomized controlled trials," "etomidate," and "remimazolam." The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. TRIAL REGISTRATION: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55948.

Wolbachia mediates crosstalk between miRNA and Toll pathways to enhance resistance to dengue virus in Aedes aegypti.

The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency.

Analysis of the chemical constituents and their metabolites in Orthosiphon stamineus Benth. via UHPLC-Q exactive orbitrap-HRMS and AFADESI-MSI techniques.

BACKGROUND: Known for its strong diuretic properties, the perennial herbaceous plant Orthosiphon stamineus Benth. is believed to preserve the kidney disease. This study compared the boiling water extract with powdered Orthosiphon stamineus Benth. and used a highly sensitive and high resolution UHPLC-Q-Exactive-Orbitrap-HRMS technology to evaluate its chemical composition. RESULTS: Furthermore, by monitoring the absorption of prototype components in rat plasma following oral treatment, the beneficial ingredients of the Orthosiphon stamineus Benth. decoction was discovered. Approximately 92 substances underwent a preliminary identification utilizing relevant databases, relevant literature, and reference standards. As the compound differences between the powdered Orthosiphon stamineus Benth. and its water decoction were analyzed, it was found that boiling produced additional compounds, 48 of which were new. 45 blood absorption prototype components and 49 OS metabolites were discovered from rat serum, and a kidney tissue homogenate revealed an additional 28 prototype components. Early differences in the distribution of ferulic acid, cis 4 coumaric acid, and rosmarinic acid were shown using spatial metabolomics. It was elucidated that the renal cortex region is where rosmarinic acid largely acts, offering a theoretical foundation for further studies on the application of OS in the prevention and treatment of illness as well as the preservation of kidney function. SIGNIFICANCE: In this study, UHPLC-Q Exactive Orbitrap-HRMS was employed to discern OS's chemical composition, and a rapid, sensitive, and broad-coverage AFADESI-MSI method was developed to visualize the spatial distribution of compounds in tissues.

Quercetin inhibits breast cancer cell proliferation and survival by targeting Akt/mTOR/PTEN signaling pathway.

Recently, natural compounds such as quercetin have gained an increasing amount of attention in treating breast cancer. However, the exact mechanisms responsible for the antiproliferative functions of quercetin are not completely understood. Therefore, we aimed to examine quercetin impacts on breast cancer cell proliferation and survival and the involvement of PI3K/Akt/mTOR pathway. Breast cancer MDA-MB-231 and MCF-7 cells were exposed to quercetin, and cell proliferation was assessed by MTT assay. ELISA was applied to evaluate cell apoptosis. The expression levels of apoptotic mediators such as caspase-3, Bcl-2, Bax and PI3K, Akt, mTOR, and PTEN were assessed via qRT-PCR and western blot. We found that quercetin suppressed dose dependently cell growth capacity in MDA-MB-231 and MCF-7 cells. In addition, quercetin treatment increase apoptosis in both cells lines via modulating the pro- and antiapoptotic markers. Quercetin upregulated PTEN and downregulated PI3K, Akt, and mTOR, hence suppressing this signaling pathway in cells. In conclusion, we showed antiproliferative and pro-apoptotic function of quercetin in breast cancer cell lines, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.

[Tongdu Tiaoshen acupuncture for subjective tinnitus:a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of Tongdu Tiaoshen acupuncture (acupuncture for promoting the circulation of the governor vessel and regulating the spirit) for subjective tinnitus, and explore its potential mechanism. METHODS: A total of 92 patients with subjective tinnitus were randomly divided into an acupuncture group (46 cases, 5 cases dropped out) and a medication group (46 cases, 2 cases dropped out). The acupuncture group received Tongdu Tiaoshen acupuncture at Shuigou (GV 26), Yintang (GV 24+), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14) and Zhongzhu (TE 3), Tinghui (GB 2), Yifeng (TE 17) on the affected side, 30 min each time, once every other day, 3 times a week. The medication group was orally administered ginkgo biloba leaves tablets (40 mg each time) and mecobalamin tablets (0.5 mg each time), 3 times a day. Both groups were treated for 4 weeks. The scores of tinnitus severity, tinnitus loudness visual analogue scale (VAS) and depression anxiety stress scale-21(DASS-21) before and after treatment were observed in the two groups, serum level of brain-derived neurotrophic factor (BDNF) before and after treatment in the two groups was detected, and the clinical effect was evaluated in the two groups. RESULTS: After treatment，the scores of tinnitus severity, tinnitus loudness VAS and DASS-21 were decreased compared with those before treatment in the two groups (P<0.01), and the scores in the acupuncture group were lower than those in the medication group (P<0.05). After treatment, the serum level of BDNF was decreased compared with that before treatment in the two groups (P<0.01), and the serum level of BDNF in the acupuncture group was lower than that in the medication group (P<0.05). The total effective rate of the acupuncture group was 82.9% (34/41), which was higher than 70.5% (31/44) in the medication group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture could improve the severity of tinnitus, tinnitus loudness and negative emotion in patients with subjective tinnitus. Its mechanism may be related to the regulation of serum level of BDNF and thus affect auditory central plasticity.

Gait Analysis with Wearable Sensors in Isolated REM Sleep Behavior Disorder Associated with Phenoconversion: An Explorative Study.

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Earthworms and lactic acid bacteria (LAB) cooperate to promote the biodegradation of tetracycline residues in livestock manure.

Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in livestock feces, and their removal is crucial for sustainable soil-ecosystem development. Physical and chemical approaches to extract tetracycline may have adverse effects on soil ecosystems, but no studies have thus far examined the potential for biological methods, such as collective degradation action of soil fauna. Thus, this study aimed to investigate the synergistic effects of lactic acid bacteria (LAB) and earthworms (Eisenia fetida) on biodegradation of tetracycline residues in sheep manure. We assessed earthworm biomass, tetracycline residue, and bacterial communities in both earthworm intestines and vermicompost. Earthworm biomass and tetracycline degradation efficiency increased significantly with LAB addition, with a degradation rate of up to 80.16%. This increase may be attributable to LAB acting as electron donors to spur tetracycline degradation. Additionally, we noted that tetracycline presence significantly influenced bacterial communities in earthworm intestines and vermicompost, elevating the abundance of potential pathogenic bacteria (e.g., Flavobacterium, Gammaproteobacteria, and Enterobacteriaceae). This finding suggests that heightened environmental stress from antibiotics could actually facilitate the growth of less prevalent bacteria, including potential pathogens. In conclusion, our study provides evidence supporting the effectiveness of LAB and earthworms in degrading tetracycline residues. In particular, LAB appears to mitigate stress from tetracycline exposure in earthworms, thus increasing their vermicomposting efficacy. Our work has important implications for soil management, with the potential to enhance pollution clean-up rates while minimizing negative side-effects to soil microbial communities.

The roles of Braun Lipoprotein in inducing tolerance of bovine endometrium infected by Escherichia coli.

Escherichia coli (E. coli), a Gram-negative bacterium, is the primary pathogen responsible for endometritis in dairy cattle. The outer membrane components of E. coli, namely lipopolysaccharide (LPS) and bacterial lipoprotein, have the capacity to trigger the host's innate immune response through pattern recognition receptors (PRRs). Tolerance to bacterial cell wall components, including LPS, may play a crucial role as an essential regulatory mechanism during bacterial infection. However, the precise role of Braun lipoprotein (BLP) tolerance in E. coli-induced endometritis in dairy cattle remains unclear. In this study, we aimed to investigate the impact of BLP on the regulation of E. coli infection-induced endometritis in dairy cattle. The presence of BLP was found to diminish the expression and release of proinflammatory cytokines (IL-8 and IL-6), while concurrently promoting the expression and release of the anti-inflammatory cytokine IL-10 in endometrial epithelial cells (EECs). Furthermore, BLP demonstrated the ability to impede the activation of MAPK (ERK and p38) and NF-κB (p65) signaling pathways, while simultaneously enhancing signaling through the STAT3 pathway in EECs. Notably, BLP exhibited a dual role, acting both as an activator of TLR2 and as a regulator of TLR2 activation in LPS- and E. coli-treated EECs. In E. coli-infected endometrial explants, the presence of BLP was noted to decrease the release of proinflammatory cytokines and the expression of HMGB1, while simultaneously enhancing the release of anti-inflammatory cytokines. Collectively, our findings provide evidence that the bacterial component BLP plays a protective role in E. coli-induced endometritis in dairy cattle.

Photoexcitation-induced efficient detoxification and removal of arsenite in contaminated water by a layered double hydroxide-supported polyacrylate stabilized ferrous sulfide composite.

The effective detoxification and removal of arsenite (As(III)) has been widely concerned because of its strong toxicity and migration ability. In this study, we designed a layered double hydroxide-supported polyacrylate stabilized ferrous sulfide composite (PAA/FeS@LDH) and coupled it with UV excitation to purify As(III)-polluted water. The removal efficiency of As(III) under UV irradiation reached almost 100% in 120 min, and the first-order kinetic constant was 3.12 orders of magnitude higher than under dark. UV irradiation significantly accelerated the oxidation and detoxification of As(III) at the interface of PAA/FeS@LDH and treatment solution. It is attributable to the generation of reactive oxygen species (ROS) intermediates, including .O2-, .OH, and SO4.- under UV irradiation, because of the presence of the photogenerated electron-hole pairs and iron valence states cycles. Importantly, .O2- may be rapidly captured and oxidized to 1O2 on the surface of PAA/FeS@LDH that is also an important contributor to the oxidation removal of As(III). Noticeably, As(III) concentrations in the real water were rapidly reduced to below the guideline limitation of drinking water (10 µg/L) within 20 min under UV irradiation. Our outcomes provide a novel photoexcitation treatment system for the efficient detoxification and removal of As from actual wastewater.

Targeting Hydrogel for Intelligent Recognition and Spatiotemporal Control in Cell-Based Therapeutics.

Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.

Superconductivity in Freestanding Infinite-Layer Nickelate Membranes.

The observation of superconductivity in infinite-layer nickelates has attracted significant attention due to its potential as a new platform for exploring high-Tc superconductivity. However, thus far, superconductivity has only been observed in epitaxial thin films, which limits the manipulation capabilities and modulation methods compared to two-dimensional exfoliated materials. Given the exceptionally giant strain tunability and stacking capability of freestanding membranes, separating superconducting nickelates from the as-grown substrate is a novel way to engineer the superconductivity and uncover the underlying physics. Herein, this work reports the synthesis of the superconducting freestanding La0.8Sr0.2NiO2 membranes ( T c zero = 10.6 K ${T}_{\mathrm{c}}^{\mathrm{zero}}\ =\ 10.6\ \mathrm{K}$ ), emphasizing the crucial roles of the interface engineering in the precursor phase film growth and the quick transfer process in achieving superconductivity. This work offers a new versatile platform for investigating superconductivity in nickelates, such as the pairing symmetry via constructing Josephson tunneling junctions and higher Tc values via high-pressure experiments.

A study on expression of GRP78 and CHOP in neutrophil endoplasmic reticulum and their relationship with neutrophil apoptosis in the development of sepsis.

We investigated the relationship between neutrophil apoptosis and endoplasmic reticulum stress (ERS) in sepsis and its mechanism. A prospective cohort study was conducted by recruiting a total of 58 patients with sepsis. Peripheral blood samples were collected on 1, 3, 5 and 7 days after admission to the ICU. The expressions of endoplasmic reticulum specific glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), apoptosis signal-regulating kinase 1 (ASK1), Bcl-2-like 11 (BIM), death receptor 5 (DR5), c-Jun N-terminal kinases (JNK) and p38 were detected by Western blot and PCR. The subcellular location of CHOP and GRP78 was observed by immunofluorescence analysis. Spearman correlation was used to analyze the correlation between the expression of chop protein and the apoptosis rate of peripheral blood neutrophils. Healthy volunteers in the same period were selected as the healthy control group. The expression of GRP78 protein was significantly elevated on the first day of ICU admission and showed a decreasing trend on the third, fifth and seventh day, but was significantly higher than the corresponding healthy control group. The expression of CHOP protein reached the highest level on the third day. The expression of chop protein in each group was significantly higher than that in the corresponding healthy control group. Immunofluorescence staining clearly showed that the CHOP protein accumulated in the nucleus, with an elevation in the intensity of GRP78. The neutrophil apoptosis rate of sepsis patients on the 1st, 3rd, 5th and 7th day of ICU stay was significantly higher than that of the healthy control group, with the highest apoptosis rate on the 3rd day, and then decreased gradually. CHOP protein expression level was significantly positively correlated with neutrophil apoptosis rate in sepsis patients. Endoplasmic reticulum stress occurs in neutrophils during the development of sepsis. GRP78 protein and CHOP protein may be involved in the pathological process of neutrophil apoptosis in sepsis.

The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

Screening and Analysis of SARS-CoV-2 Antibody Among Unvaccinated Blood Donors in Chongqing, China.

OBJECTIVE: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody among unvaccinated voluntary blood donors in Chongqing, and to provide evidence for epidemic surveillance. METHODS: A total of 10,208 voluntary blood donors from January 5 to January 20, 2021, in the Chongqing area were collected, and the SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies were detected by chemiluminescence, and the differences of antibody-positive rate in different gender, age, ABO blood group, and different risk areas were analyzed. RESULTS: Among 10208 blood donors, 10 were found to be positive for SARS-COV-2 IgG antibody, giving a positivity rate of SARS-COV-2 IgG at 0.10%, and 29 were positive for SARS-CoV-2 IgM antibody, with a positivity rate of SARS-CoV-2 IgM at 0.28%. There was no statistical difference in the positive rate of antibody among different genders, ages, and ABO blood types, but it was related to the number of confirmed coronavirus disease 2019 (COVID-19) cases in each city. CONCLUSIONS: The SARS-CoV-2 seroprevalence rate in Chongqing was low and correlated with the number of confirmed COVID-19 cases.

Comparison of the Efficacy and Prognostic Factors of Endoscopic Submucosal Dissection with Different Procedures for Colorectal Neuroendocrine Tumors.

Objective: To compare the clinical efficacy, prognostic factors, and survival impact of endoscopic submucosal dissection (ESD) versus endoscopic submucosal resection (ESR) in patients with colorectal neuroendocrine tumors (NETs). Methods: This retrospective study analyzed 118 patients with colorectal NETs treated from January 2012 to December 2020. Patients were divided into the ESD group (n=59) and the ESR group (n=59) based on the surgical treatment method. We assessed the surgical efficacy, long-term survival, and factors influencing tumor recurrence using logistic regression analysis with clear criteria for group division. Results: En bloc resection, complete histological resection rates, and postoperative complications did not significantly differ between groups (P > .05). In the 33 patients with recurrence, those with tumor diameter < 10 mm, tumor grade G1, and negative resection margins were significantly fewer (P < .05). Logistic regression identified tumor diameter, grade, and resection margin status as significant predictors of recurrence (P < .05). There was no significant difference in distant metastasis, survival rates, and mortality between the groups (P > .05). Conclusions: ESD and ESR offer high clinical efficacy in treating colorectal NETs without significantly impacting prognosis or long-term survival. ESD, however, may be more suited for larger tumors due to its precise tissue removal capability. Future research should explore the long-term outcomes over 3 and 5 years to further validate these findings.

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders.

Background: Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events. Methods: We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines. Results: In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics. Conclusion: We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5's interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO's genetic basis, suggesting potential therapeutic targets for future research.

Pan-cancer single-cell landscape of drug-metabolizing enzyme genes.

OBJECTIVE: Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy. METHODS: Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity. RESULTS: Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin). CONCLUSION: Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.

Lymph node dissection before initial treatment for locally advanced cervical cancer: A systematic review and meta-analysis.

The effectiveness of removing lymph nodes before initial treatment in patients with locally advanced cervical cancer is still debated. This article presents a meta-analysis that systematically evaluates the impact of this approach on oncological outcomes. A systematic literature search of PubMed, Embase, Science Direct, and the Cochrane Database of Systematic Reviews (up to December 2023) was performed to obtain relevant studies. The findings were combined using fixed-effects models to address potential differences. Combined risk ratios (HR) and 95% confidence intervals (CI) were calculated. Egger's test was used to assess publication bias. Out of 1025 screened articles, four studies (involving 838 women) met the inclusion criteria. The results showed that lymph node dissection before initial treatment did not affect overall survival (OS) in patients with locally advanced cervical cancer compared to concurrent radiotherapy (HR = 1.11, 95% CI = 0.91-1.36, P = 0.30). It also did not increase the incidence of postoperative complications or cause delays in radiotherapy. In particular, removing larger lymph nodes (>2cm) aided in defining the radiation field and decreasing radiotherapy-related complications. The surgical technique also had some impact on postoperative complications. In summary, in order to obtain the best therapeutic outcomes, personalized plans should be developed for each patient, accounting for their individual circumstances to achieve precise treatment and enhance their quality of life.