The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Objective:To investigate the effect of glabridin on neutrophil extracellular traps (NETs) formation and pyroptosis in rats with sepsis-induced lung injury.Methods:Twenty-four male Wistar rats were divided into three groups according to the random number table method. The sepsis group was established by cecal ligation and puncture (CLP). The Glabridin group underwent CLP and glabridin gavage (30 mg/kg)(CLP+GLA). The sham operation group underwent cecal exploration, and only the abdomen was closed after cecal turning(Sham). After 12 hours, plasma、alveolar lavage fluid and lung tissue samples were taken for detection . Then, protein content of the alveolar lavage fluid was determined; The wet/dry weight(W/D) ratio of the lung tissue was determined; The pathological changes in lung tissue were observed after hematoxylin-eosin (HE) staining. The levels of NETs marker MPO-DNA complex and related inflammatory factors IL-18 and IL-1β in plasma were detected by enzyme-linked immunosorbent assay. The changes of Caspase-1and Cleaved-caspase-1 protein in lung tissue were detected by Western blot.Results:The total protein concentration of alveolar lavage fluid was significantly higher in the sepsis group compared with the Sham group ( P<0.01), and it decreased in the glabridin group compared with the sepsis group ( P<0. 05). Significant aggravation of pulmonary edema in the sepsis group, and the glabridin group reduced pulmonary edema compared with the sepsis group.The pathological results of lung tissue under the light microscope showed: The structure of lung tissue in the Sham group was normal, and the alveoli were clear; In the sepsis group, the alveolar wall was thickened widely and inflammatory cells infiltrated obviously; Compared with the sepsis group, the lung tissue injury was significantly reduced in the light licorice group. The enzyme-linked immunosorbent assay results showed that the levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the plasma of the sepsis group were significantly higher than those in the Sham group ( P<0.001). The levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the glabridin group were significantly lower than those in the sepsis group (MPO-DNA: P<0. 01; IL-18、IL-1β: P<0.05) . Western blot Technical results showed that the expression of Caspase-1 and Cleaved-caspase-1 protein positive signal was significantly enhanced in the lung tissue of the rats in the sepsis group compared with the Sham group; the distribution of Caspase-1 positive cells in the lung tissue of the sepsis + glabridin group was similar to that of the Sham group, and the expression of Cleaved-caspase-1 positive signal was higher than that of the Sham group. Conclusions:Glabridin can effectively reduce lung inflammation and play a protective role in lung injury in septic rats by inhibiting NETs production and pyroptosis.

Objective To elucidate the causal relationship between high-density lipoprotein cholesterol(HDL-C)and colorectal cancer(CRC)through Mendelian randomization.Methods Mendelian randomi-zation analysis was conducted using genetic instrumental variables selected from a genome-wide association study dataset.The main methods included inverse variance weighted,MR-Egger,weighted median,simple mode,and weighted mode method;among which,inverse variance weighted method served as the primary analytical approach.Sensitivity analyses were performed to verify the robustness of results.Results A total of 41 genetic instrumental variables associated with HDL-C were identified.Inverse variance weighted method(OR=0.84,95% CI:0.73-0.96,P=0.01)and weighted median method(OR=0.82,95% CI:0.67-0.99,P=0.04)indicated a negative correlation between genetically-determined HDL-C and CRC risk.Sensitivity analyses confirmed the absence of heterogeneity and horizontal pleiotropy(P>0.05).Conclusion A causal relationship exists between HDL-C and CRC risk,with rs1077834 as a potential key determinant in the influence of HDL-C on CRC risk.

Objective To evaluate the efficacy and safety of fluorouracil and leucovorin and oxaliplatin(FOLFOX)regimen hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib(LEN)and immune checkpoint inhibitors(ICIs)in treating patients with hepatocellular carcinoma(HCC)after the occurrence of transcatheter arterial chemoembolization(TACE)refractoriness.Methods The clinical data of 54 HCC patients who developed TACE refractoriness,were admitted to the Jiangsu Provincial Cancer Hospital of China to receive FOLFOX-HAIC combined with LEN and ICIs therapy between January 2019 and December 2022,were retrospectively analyzed.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to statistically analyze the clinical efficacy,the Common Terminology Criteria For Adverse Events version 5.0(CTCAE 5.0)was adopted to record and evaluate the treatment-related adverse events(TRAEs).The primary endpoints were progression-free survival(PFS)and overall survival(OS),the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and safety.Results The median PFS was 11.7 months(95％CI:8.124-15.276 months),the median OS was 23.1 months(95％CI:19.508-26.692 months),the ORR was 46.3％,and the DCR was 87.0％.The most common TRAE at all levels was elevated alanine aminotransferase(51.9％),and the most common TRAE of grade 3/4 was hypertension(9.3％).No treatment-related death occurred.Conclusion For the treatment of HCC patients who developed TACE refractoriness,FOLFOX-HAIC combined LEN and ICIs is clinically safe and effective.(J Intervent Radiol,2024,33:610-615)

OBJECTIVE: To investigate the development present situation of the department of critical care medicine in Inner Mongolia Autonomous Region (hereinafter referred to as Inner Mongolia), in order to promote the standardized and homogeneous development of critical care medicine in Inner Mongolia, and also provide a reference for discipline construction and resource allocation. METHODS: A survey study was conducted in comprehensive intensive care unit (ICU) of tertiary and secondary hospitals in Inner Mongolia by online questionnaire survey and telephone data verification. The questionnaire was based on the Guidelines for the Construction and Management of Intensive Care Units (Trial) (hereinafter referred to as the Guidelines) issued by the National Health Commission in 2009 and the development trend of the discipline. The questionnaire covered six aspects, including hospital basic information, ICU basic information, personnel allocation, medical quality management, technical skill and equipment configuration. The questionnaire was distributed in September 2022, and it was filled out by the discipline leaders or department heads of each hospital. RESULTS: As of October 24, 2022, a total of 101 questionnaires had been distributed, 85 questionnaires had been recovered, and the questionnaire recovery rate had reached 84.16%, of which 71 valid questionnaires had been collected in a total of 71 comprehensive ICU. (1) There were noticeable regional differences in the distribution of comprehensive ICU in Inner Mongolia, with a relatively weak distribution in the east and west, and the overall distribution was uneven. The development of critical care medicine in Inner Mongolia was still lacking. (2) Basic information of hospitals: the population and economy restricted the development of ICU. The average number of comprehensive ICU beds in the western region was only half of that in the central region (beds: 39.0 vs. 86.0), and the average number of ICU beds in the eastern region was in the middle (83.6 beds), which was relatively uneven. (3) Basic information of ICU: among the 71 comprehensive ICU surveyed, there were 44 tertiary hospitals and 27 secondary hospitals. The ratio of ICU beds to total beds in tertiary hospitals was significantly lower than that in secondary hospitals [(1.59±0.81)% vs. (2.11±1.07)%, P < 0.05], which were significantly lower than the requirements of the Guidelines of 2%-8%. The utilization rate of ICU in tertiary and secondary hospitals [(63.63±22.40)% and (44.65±20.66)%, P < 0.01] were both lower than the bed utilization rate required by the Guidelines (75% should be appropriate). (4) Staffing of ICU: there were 376 doctors and 1 117 nurses in tertiary hospitals, while secondary hospitals had 122 doctors and 331 nurses. There were significant differences in the composition ratio of the titles of doctors, the degree of doctors, and the titles of nurses between tertiary and secondary hospitals (all P < 0.05). Most of the doctors in tertiary hospitals had intermediate titles (attending physicians accounted for 41.49%), while most of the doctors in secondary hospitals had junior titles (resident physicians accounted for 43.44%). The education level of doctors in tertiary hospitals was generally higher than that in secondary hospitals (doctors: 2.13% vs. 0, masters: 37.24% vs. 8.20%). The proportion of nurses in tertiary hospitals was significantly lower than that in secondary hospitals (17.01% vs. 24.47%). The ratio of ICU doctors/ICU beds [(0.64±0.27)%, (0.59±0.34)%] and ICU nurses/ICU beds [(1.76±0.56)%, (1.51±0.48)%] in tertiary and secondary hospitals all failed to meet the requirements above 0.8 : 1 and 3 : 1 of the Guidelines. (5) Medical quality management of ICU: compared with secondary hospitals, the proportion of one-to-one drug-resistant bacteria care in tertiary hospitals (65.91% vs. 40.74%), multimodal analgesia and sedation (90.91% vs. 66.67%), and personal digital assistant (PDA) barcode scanning (43.18% vs. 14.81%) were significantly higher (all P < 0.05). (6) Technical skills of ICU: in terms of technical skills, the proportion of bronchoscopy, blood purification, jejunal nutrition tube placement and bedside ultrasound projects carried out in tertiary hospitals were higher than those in secondary hospitals (84.09% vs. 48.15%, 88.64% vs. 48.15%, 61.36% vs. 55.56%, 88.64% vs. 70.37%, all P < 0.05). Among them, the placement of jejunal nutrition tube, bedside ultrasound and extracorporeal membrane oxygenation were mainly completed independently in tertiary hospitals, while those in secondary hospitals tended to be completed in cooperation. (7) Equipment configuration of ICU: in terms of basic equipment, the ratio of the total number of ventilators/ICU beds in tertiary and secondary hospitals [0.77% (0.53%, 1.07%), 0.88% (0.63%, 1.38%)], and the ratio of injection pump/ICU beds [1.70% (1.00%, 2.56%), 1.25% (0.75%, 1.88%)] didn't meet the requirements of the Guidelines. The equipment ratio was insuffcient, which means that the basic needs of development had not been met yet. CONCLUSIONS The development of comprehensive ICU in Inner Mongolia has tended to mature, but there is still a certain gap in the development scale, personnel ratio and instruments and equipment compared with the Guidelines. Moreover, the comprehensive ICU appears the characteristics of relatively weak eastern and western regions, and the overall distribution is uneven. Therefore, it is necessary to increase efforts to invest in the construction of the department of critical care medicine.
Humans ; Intensive Care Units ; Critical Care ; Surveys and Questionnaires ; Tertiary Care Centers ; China

Objective    To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods    The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results    After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion    Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.

OBJECTIVE：To put forward some suggestions for the implementation of OTC monograph in China. METHODS ： Literature research was used to comprehensively review the concept ，emergence and development ，function of OTC monograph in USA；referring to experience in USA ，the necessity and feasibility of monograph system for OTC registration and evaluation in China were explored ，and some suggestions were put forward to the implementation of OTC monograph in China. RESULTS & CONCLUSIONS：OTC monograph in USA refers to the regulatory standards that should be followed when selling OTC products not included in new drug applications. The monograph originates from the re-evaluation project of the effectiveness of OTC drugs ， which plays a special role in accelerating the drug marketing and promoting product innovation. The OTC monograph system is necessary to help to optimize the OTC registration and evaluation ，but at present ，the conditions to establish and implement OTC monograph are not yet ripe in China. Based on the optimization of resource allocation and infrastructure construction ，national OTC drug management experience ，OTC monograph can play a full part in OTC registration and evaluation ，in terms of carrying out in-depth research ，taking pilot test ，improving risk management system and enhancing drug review resource allocation ability.

BACKGROUND: AND PURPOSE: Previous studies have explored the association between retinal vascular changes and cognitive impairment. The retinal vasculature shares some characteristics with the cerebral vasculature, and quantitative changes in it could indicate cognitive impairment. Hence, a comprehensive meta-analysis was performed to clarify the potential relationship between retinal vascular geometric changes and cognitive impairment. METHODS: Relevant databases were scrupulously and systematically searched for retinal vascular geometric changes including caliber, tortuosity, and fractal dimension (FD), and for cognitive impairment. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of included studies. RevMan was used to perform the meta-analysis and detect publication bias. Sensitivity analyses were also performed. RESULTS: Five studies that involved 2,343 subjects were finally included in the meta-analysis. The results showed that there was no significant association between central retinal artery equivalents (Z=1.17) or central retinal venular equivalents (Z=1.74) and cognitive impairment (both p>0.05). Similarly, no significant difference was detected in retinal arteriolar tortuosity (Z=0.91) and venular tortuosity (Z=1.31) (both p>0.05). However, the retinal arteriolar FD (mean difference: −0.03, 95% CI: −0.05, −0.01) and venular FD (mean difference: −0.03, 95% CI: −0.05, −0.02) were associated with cognitive impairment. CONCLUSIONS A smaller retinal microvascular FD might be associated with cognitive impairment. Further large-sample and well-controlled original studies are required to confirm the present findings.