Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Objective:To investigate the value of high-flow oxygen therapy after weaning in successful extubation of critically ill patients with mechanical ventilation.Methods:A retrospective study was conducted. The weaned patients who were older than 18 years old and underwent mechanical ventilation for the first time due to cerebrovascular accidents, surgical operations, cardiovascular diseases, and pneumonia admitted to the department of critical care medicine of Zhejiang Hospital from January 2018 to June 2020 were enrolled. Among the patients, 40 cases received high-flow oxygen therapy after weaning, and 37 cases received Venturi combined with the humidifier. The patient's gender, age, primary disease, severity score, duration of mechanical ventilation before weaning, heart rate (HR), blood pressure, pulse oxygen saturation (SpO 2) at 0, 6, 12, 18, and 24 hours after weaning, and pH value, arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2) at 6, 12, 18, and 24 hours after weaning, the rate of performing mechanical ventilation after weaning, extubation time after weaning, and the rate of reintubation after extubation for 72 hours were collected. Results:There was no significant difference in baseline data such as gender, age, primary disease, severity score, and duration of mechanical ventilation before weaning between the two groups. After weaning, the vital signs of the two groups were stable, and there was no significant difference in HR, systolic blood pressure (SBP), diastolic blood pressure (DBP) or SpO 2 at each time point between the two groups. After weaning, the pH of arterial blood gas analysis in the two groups and the fluctuations of PaO 2 and PaCO 2 in the high-flow group were not obvious. In the Venturi group, PaO 2 gradually decreased after weaning, PaCO 2 increased significantly at 12 hours, and slowly decreased after 12 hours. The PaO 2 from 6 hours and PaCO 2 from 12 hours in the high-flow group were significantly lower than those in the Venturi group, and continued to 24 hours [PaO 2 (mmHg, 1 mmHg≈0.133 kPa): 112.34±38.25 vs. 156.76±68.44 at 6 hours, 110.92±38.66 vs. 150.64±59.07 at 12 hours, 111.12±36.77 vs. 141.30±39.05 at 18 hours, 110.82±39.37 vs. 139.65±41.50 at 24 hours; PaCO 2 (mmHg): 41.30±7.51 vs. 47.42±7.54 at 12 hours, 40.97±6.98 vs. 45.83±8.63 at 18 hours, 40.10±7.06 vs. 46.14±9.15 at 24 hours, all P < 0.01]. The rate of performed mechanical ventilation after weaning and the rate of reintubation after extubation for 72 hours in the high-flow group were significantly lower than those in the Venturi group [17.5% (7/40) vs. 40.5% (15/37), 6.2% (2/32) vs. 31.8% (7/22), both P < 0.05], and the extubation time after weaning was significantly shorter than that in the Venturi group (hours: 22.43±11.72 vs. 28.07±10.42, P < 0.05). Conclusion:Using high-flow oxygen therapy to the extubation process of critically ill mechanical ventilation patients can reduce the incidence of carbon dioxide retention and the rate of performed mechanical ventilation after weaning, shorten the extubation time after weaning, and reduce the rate of reintubation after extubation for 72 hours.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown. This study aimed to investigate this association in a community-dwelling population aged ≥ 40 years in Shanghai, China. Oral glucose tole3rance test was conducted during baseline and follow-up visits. Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk. A total of 613 (10.3%) incident diabetes cases were identified during the follow-up visit after 4.5 years. Fasting plasma glucose, postload glucose, and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid (all Ps < 0.05). The incidence rate of diabetes increased across the quartiles of serum uric acid (7.43%, 8.77%, 11.47%, and 13.43%). Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid (odds ratio (95% confidence interval) = 1.36 (1.06-1.73)). Stratified analysis indicated that the association was only observed in women. Accordingly, serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.
Adult ; Aged ; China/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Uric Acid

Objective:To study the genotype distribution of drug-related gene polymorphism of methotrexate (MTX) and leflunomide (LEF) in patients with rheumatoid arthritis (RA).Methods:The genotyping results of RA patients' MTX and LEF related genes(MTHFR677C/T, MTHFR1298A/C, ABCB13435T/C, DHODH19C/A and CYP1A2734C/A) detected in Shanghai Guanghua Hospital from December 2018 to May2019 and drug-related adverse effect were statisticallyanalyzed. The independence of allele distribution was tested by Hardy-Weinberg test. Counting data of genotypes and allele frequencies among the groups were analyzed by the chi-square test. Measurement data were showed as Mean±SD deviation. The network between incidence of adverse events and genotypes of patients was analyzed by cytoscape software. Results:Genotype distribution in 151 patients was consistent with Hardy-Weinberg genetic balance ( P>0.05), and genotype and allele distribution of each gene showed no statistical difference in gender ( P>0.05). The results showed that the most common genotype in RA were that genotypes of the good response with moderate resistance to MTX (MTHFR677CC/MTHFR1298AA/ABCB13435CT) (16 cases, 13.5%) and the good response with moderate side effect risk to LEF(DHODH19CC/CYP1A2734AC) (25 cases, 28.4%). According to the distribution frequency of alleles, the incidence of high side effects caused by MTX combined with LEF was predicted to be 2.9%, which was close to 1.8% of the actual genotypes of patients. The types and proportion of clinical adverse reactions in patients were retrospectively analyzed and the correlation network analysis was conducted with the genotype analysis results. It was found that the incidence rates of adverse reactions were liver injury (35.4%, 35/99), leukopenia (14.1%, 14/99), thrombocytopenia (2.0%, 2/99), and skin rash (1.0%, 1/99) from the top to the bottom. The top two genotypes that were related to the occurence of adverse events were MTHFR677CT/MTHFR1298AA/ABCB13435CT and DHODH19CA/CYP1A2734AC, respectively, which verified the consistency between drug-related genotype and clinical manifestations in RA patients. Conclusion:Our results suggested that genotype in RA patients is closely related to drug efficacy and adverse events. 2.9% of RA patients need to stop taking MTX and LEF due to high MTX resistance and poor MTX response and increased toxicity when combined with LEF, in which the proportion of liver injury is the highest.

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

With the development of critical care ultrasound technology, clinics begins to pay attention to the role of critical care ultrasound in nursing of critically ill patients. The increasingly extensive application of ultrasound in the field of critical care provides a visual tool for clinical nursing work, which can qualitatively and quantitatively evaluate nursing indicators, help to solve the existing nursing problems and nursing difficulties and promote the improvement of critical care quality and the development of nursing academics. To this end, experts formulates this consensus based on years of experience and application of intensive care ultrasound practice.

Objective? To construct the perioperative urinary incontinence nursing outcomes intervention plan suitable for elderly patients with rectal cancer. Methods? From December 2017 to June 2018, we preliminarily developed the perioperative urinary incontinence nursing plan for elderly patients with rectal cancer by literature review and case investigation. We selected 11 experts undertaking rectal cancer and urinary incontinence clinical care, clinical nursing and nursing management by purpose sampling in Shanghai to demonstrate the intervention plan with the method of expert meeting so as to confirm the final intervention plan. Results? The expert authority coefficient was 0.93. The nursing plan included 4 primary indexes, 9 secondary indexes and 42 tertiary indexes. Conclusions? The expert authority coefficient is high in this study. The construction of perioperative urinary incontinence nursing plan based on nursing outcomes classification system for elderly patients with rectal cancer provides the reference for carrying out practice and researches of perioperative urinary incontinence management for elderly patients with rectal cancer.