OBJECTIVE: To investigate the predictive value of sphinor kinase 1 (sphk1), D-lactic acid, and intestinal fatty acid binding protein (I-FABP) for gastrointestinal injury in patients with sepsis. METHODS: A prospective observational study was conducted. Sixty-eight patients with sepsis and gastrointestinal dysfunction admitted to the department of critical care medicine of the First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and Technology from May 2024 to March 2025 were enrolled (sepsis group), and they were divided into acute gastrointestinal injury (AGI) I-IV groups according to the definition and grading criteria of AGI proposed by the European Society of Intensive Care Medicine in 2012. Twenty non-sepsis patients without AGI admitted to the intensive care unit during the same period were enrolled as the control group (non-sepsis group). Within 30 minutes of patient enrollment, plasma sphk1, D-lactic acid, and I-FABP levels were determined by enzyme linked immunosorbent assay (ELISA). General data such as gender, age were recorded, and levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactic acid (Lac), and acute physiology and chronic health evaluation II (APACHEII), sequential organ failure assessment (SOFA) were measured. Spearman method was used to analyze the correlation between sphk1, I-FABP, D-lactic acid and other indicators. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score for gastrointestinal injury in patients with sepsis. RESULTS: Among the 68 sepsis patients, 13 were classified as AGI grade I, 16 as AGI grade II, 23 as AGI grade III, and 16 had AGI grade IV. There were no statistically significant differences in gender, age, and abdominal infection rate among the groups. The SOFA score and APACHEII score of the sepsis group were significantly higher than those of the non-sepsis group; and the APACHEII score of the AGI IV group was significantly higher than that of the AGI I and AGI II groups. The levels of sphk1, D-lactic acid, I-FABP, PCT, Lac and hs-CRP in the sepsis group were significantly higher than those in the non-sepsis group, and each indicator gradually increased with the increase of AGI grade. Correlation analysis showed that plasma sphk1, D-lactic acid, and I-FABP in patients with sepsis-induced gastrointestinal injury were positively correlated with PCT, Lac, APACHEII score, and AGI grade (all P < 0.05), and sphk1 was positively correlated with I-FABP and D-lactic acid (r values were 0.773 and 0.782, respectively, both P < 0.05). ROC curve analysis showed that sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score had high predictive value for gastrointestinal injury in patients with sepsis, with area under the curve (AUC) of 0.996, 0.987, 0.976, 0.901, and 0.934 (all P < 0.05). When the optimal cut-off value of sphk1 was 60.46 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of D-lactic acid was 1 454.3 μg/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of I-FABP was 0.91 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of APACHEII score was 14.5, the sensitivity and specificity were 80.9% and 85.0%, respectively; when the optimal cut-off value of SOFA score was 3.5, the sensitivity and specificity were 85.3% and 95.0%, respectively. CONCLUSIONS The levels of plasma sphk1, I-FABP, and D-lactic acid were significantly elevated in patients with sepsis and gastrointestinal injury. These indicators can serve as sensitive and relatively specific serological markers for early prediction of intestinal mucosal damage.
Humans ; Lactic Acid/blood* ; Fatty Acid-Binding Proteins/blood* ; Sepsis/complications* ; Prospective Studies ; Male ; Female ; Middle Aged ; Predictive Value of Tests ; Adult ; Aged ; Gastrointestinal Diseases/blood* ; Prognosis

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Humans ; Angina, Stable ; COVID-19 ; Risk Factors ; Patients

Objective:To explore the clinical value of semi-ex vivo intestinal autotrans-plantation (IATx) for patients with mesenteric root regional tumors accompanied by vascular invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 6 patients who underwent semi-ex vivo IATx in the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital from September 2021 to December 2022 were collected. There were 4 males and 2 females, aged (47±21)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented by Mean± SD. Count data were represented by absolute numbers. Results:(1) Surgical conditions. All 6 patients completed semi-ex vivo IATx successfully. The operation time, warm ischemia time, cold ischemia time, volume of intraoperative blood transfusion were (10.2±2.1)hours, (2.3±1.6)minutes, (49.2±15.6)minutes, (707±263)mL. Of the 6 patients, 3 patients were intraoperatively perfused with cold UW solution, while the other 3 were not. (2) Postoperative conditions. Results of postoperative pathological examination of the 6 patients showed 4 cases of pancreatic ductal adenocarcinoma, 1 case of cholangiocarcinoma, and 1 case of mesenteric fibromatosis. All 6 cases had nega-tive surgical margins and the duration of postoperative hospital stay was (19±4)days. None of the patient had gastrointestinal bleeding or anastomotic leakage postoperatively, and the autotransplanted intestine functioned well. There was no perioperative death, and intravenous rehydration was not required after discharge. (3) Follow-up. All 6 patients were followed up for (12±5)months. Only 1 patient with mesenteric fibromatosis had recurrence in the 7th month postoperatively, while the remaining 5 patients showed no sign of recurrence or metastasis. There were 4 of 6 patients with chronic diarrhea. They were improved after oral loperamide, bifidobacterium and pancreatin capsules. All 6 patients survived.Conclusion:Semi-ex vivo IATx for the treatment of patients with mesenteric root regional tumors accompanied by vascular invasion is safe and feasible, which can achieve good short-term efficacy.

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

Objective:To explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and the adverse reactions.Methods:A total of 69 patients with NSCLC diagnosed in the No. 901 Hospital of the Chinese People′s Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020, and were divided into chemotherapy alone group (docetaxel+ cisplatin was used), apatinib group A [apatinib (0.25 g)+ docetaxel+ cisplatin was used] and apatinib group B [apatinib (0.50 g)+ docetaxel+ cisplatin was used] according to random number table method, with 23 cases in each group. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS), median progression-free survival (PFS), and incidences of adverse reactions were compared between the three groups of patients.Results:One patients in the apatinib group B withdrew from the study due to acute myocardial infarction. After 4 cycless of treatment, the ORR of the patients in the chemotherapy alone group, apatinib group A and apatinib group B were 17.39% (4/23), 47.83% (11/23) and 54.55% (12/22) respectively, with a statistically significant difference ( χ2=7.41, P=0.024). The ORR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=6.77, P=0.009). There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.85, P=0.028; χ2=0.20, P=0.652). The DCR of the patients in the three groups were 47.83% (11/23), 78.26% (18/23) and 86.36% (19/22) respectively, with a statistically significant difference ( χ2=9.03, P=0.011). The DCR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=7.52, P=0.006). There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.57, P=0.033; χ2=0.51, P=0.477). The median OS of the patients in the three groups were 6.8, 9.2 and 9.9 months respectively, with a statistically significant different ( χ2=8.91, P=0.022). Compared with the chemotherapy alone group, the median OS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.25, P=0.036; χ2=8.60, P=0.029). Compared with the apatinib group A, the median OS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.54, P=0.201). The median PFS of the patients in the three groups were 5.2, 7.7 and 8.2 months respectively, with a statistically significant different ( χ2=8.79, P=0.026). Compared with the chemotherapy alone group, the median PFS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.01, P=0.039; χ2=8.36, P=0.031). Compared with the apatinib A group, the median PFS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.68, P=0.186). There were statistically significant differences in the incidences of fatigue [34.78% (8/23) vs. 65.22% (15/23) vs. 72.73% (16/22), χ2=7.50, P=0.024], hypertension [4.35% (1/23) vs. 34.78% (8/23) vs. 68.18% (15/22), χ2=20.07, P<0.001], hand-foot syndrome [4.35% (1/23) vs. 43.48% (10/23) vs. 72.73% (16/22), χ2=22.28, P<0.001] and oral mucositis [8.70% (2/23) vs. 39.13% (9/23) vs. 72.73% (16/22), χ2=19.26, P<0.001] among the three groups. Compared with the chemotherapy alone group, the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue, hypertension, hand-foot syndrome and oral mucositis in the apatinib group B were increased, with statistically significant differences ( χ2=6.77, P=0.009; χ2=9.68, P=0.002; χ2=6.51, P=0.011; χ2=20.00, P<0.001; χ2=22.37, P<0.001; χ2=19.21, P<0.001). Conclusion:Apatinib (0.50 g) combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC. Apatinib (0.25 g) and apatinib (0.50 g) can prolong the survival of patients, but increasing the treatment dose can not achieve longer survival benefit.

[摘 要] 目的：探讨贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患者的近期疗效和不良反应，并随访生存情况。方法：选取中国人民解放军联勤保障部队第九〇一医院2018年1月至2019年12月收治的76例铂类耐药复发性卵巢上皮性癌患者，采用数字随机分组法分为对照组38例、观察组38例，对照组给予多柔比星脂质体单药化疗4个周期，观察组给予贝伐珠单抗联合多柔比星脂质体化疗4个周期，观察两组患者治疗后近期疗效和不良反应，以及血清肿瘤标志物人附睾蛋白4（human epididymis protein 4，HE4）、糖类抗原125（carbohydrate antigen 125，CA125）变化，并随访总生存期（OS）和无疾病进展生存期（PFS）。结果：对照组患者客观有效率（ORR）为40.54%、疾病控制率（DCR）为67.57%，观察组患者ORR为69.44%、DCR为88.89%，观察组ORR和DCR显著高于对照组（均P<0.05）。治疗后观察组患者血清HE4和CA125分别为（142.67±46.81）pmol/L、（31.79±11.65）U/L，显著低于对照组患者的（219.33±75.67）pmol/L、（57.05±17.85）U/L（均P<0.05）。两组患者的胃肠反应、骨髓抑制、肝肾功能损伤、心脏毒性、过敏反应、血栓栓塞和出血等不良反应相比较差异无统计学意义（均P>0.05）；观察组患者高血压发生率显著高于对照组（P<0.05），但可控、可耐受。观察组患者中位OS 和中位PFS分别分别为17.2个月和10.9个月，显著长于对照组患者的14.1个月和7.8个月（均P<0.05）。结论：对于铂类耐药复发性卵巢上皮性癌患者，贝伐珠单抗联合多柔比星脂质体近期疗效可靠、安全性好、不良反应可耐受，值得临床推广。

Objective:To prepare 18F-Alfatide Ⅱ automatically based on the improved CFN-100 fluorine multifunctional module and assess its PET/CT imaging in prostate cancer patients. Methods:A certain volume (200-500 μl) of fluoride ion was separated into the reaction tube by a fluoride ion separator and reacted with the labeled precursor l, 4, 7-triazacylononane-1, 4, 7-triacetic acid-E[(polyethylene glycol) 4-cyclo(Arg-Gly-Asp- D-Phe-Tyr)] 2(NOTA-E[PEG 4-c(RGDfk)] 2) (lyophilized kit). In the aqueous phase, 18F was chelated with aluminum. After being separated and purified by C18 column, 18F-Alfatide Ⅱ was prepared automatically. The radiochemical yield and its quality were analyzed. Quality control was carried out and 18F-Alfatide Ⅱ PET/CT imaging was performed in 2 patients (72 and 66 years old)with prostate cancer. Results:18F-Alfatide Ⅱ was prepared automatically by the improved CFN-100 fluorine multifunctional module combined with a double channel-fluorine ion separation device. 18F-Alfatide Ⅱ was synthetized in about 30 min, with radiochemical yield of (28±3)% (non-decay corrected, n=6). The radiochemical purity of the product was more than 98%, the specific activity was 2.8×10 7 MBq/mmol and the nuclear purity was >99%. PET/CT imaging of 2 patients showed that 18F-Alfatide Ⅱ were highly concentrated in prostate cancer lesions with the maximum standardized uptake value (SUV max) of 35.6 and 5.0, respectively. Conclusion:18F-Alfatide Ⅱ can be prepared successfully by improved CFN-100 fluorine multifunctional module with stable synthesis method, short synthesis time and high radiochemical yield, which can be highly concentrated in prostate cancer.

Objective:To explore the predictive value of complement and coagulation indicators in sepsis related acute kidney injury (AKI).Methods:Clinical data of 217 patients with sepsis admitted to the Department of Internal Medicine and Intensive Care Unit of Affiliated Hospital of Jiangnan University from January 2018 to June 2019 were retrospectively analyzed. All patients were divided into sepsis with AKI group and without AKI group. Laboratory indicators of all patients were collected, including complement C 3, complement C 4, activated partial thrombin time (APTT), prothrombin time (PT), international normalized ratio (INR), D-dimer, procalcitonin(PCT), etc. logistic regression analysis was used to explore the risk factors of sepsis related AKI. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of independent risk factors. Results:Among 217 patients, 120 patients developed sepsis related AKI and 97 patients didn′t. PCT, lactic acid, PT, APTT, INR and D-dimer in AKI patients were significantly higher than those without AKI ( P<0.01). Complement C 3 and complement C 4 were significantly lower in AKI group ( P<0.01). Multivariate logistic regression analysis suggested that blood pressure<90/60 mmHg (1 mmHg=0.133 kPa)( OR=3.705, 95% CI 1.536-8.934, P=0.004), increased lactic acid ( OR=1.479, 95% CI 1.089-2.008, P=0.012), decreased complement C 3 ( OR=0.027, 95% CI 0.005-0.152, P<0.001) and prolonged APTT ( OR=1.090, 95% CI 1.047-1.137, P<0.001)were independent risk factors predicting AKI. The area under the ROC curve (AUC) of these multivariates were 0.741 (95% CI 0.675-0.807), 0.798 (95% CI 0.732-0.864), 0.712 (95% CI 0.643-0.781) and 0.716 (95% CI 0.648-0.783) respectively. The relevant sensitivity was 57.5%, 80.8%, 87.5%, 59.2%, and the specificity was 90.7%, 75.3%, 51.5%, 77.3%, respectively. The AUC of the combined four indicators was 0.880 (95 %CI 0.835-0.926) with the sensitivity 75.0% and the specificity 90.7%. Conclusion:The low level of complement C 3 and prolonged APTT predict sepsis related AKI, and the predictive value can be enhanced if hypotension and hyperlactacidemia are added.