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

Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.

Objective:To observe the effects of adipose-derived stem cells(ADSC)combined with acellular scaffold(AS)on the ultrastructure of dorsal root ganglion and the protein and mRNA expression levels of ciliary neurotrophic factor(CNTF),Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phosphorylated STAT3(p-STAT3)in the rats with sciatic nerve injury(SNI),and to clarify the protective effect of ADSC combined with AS on dorsal root ganglion in the SNI rats and its possible mechanism.Methods:The rat ADSCs were isolated and cultured and their multidirectional differentiation potential was detected.The AS of rats was prepared,and ADSCs were injected into the AS to construct tissue-engineered nerve.A total of 36 rats were randomly divided into control group,model group,AS group,and ADSC+AS group.The rats in control group were routinely fed,and the rats in other groups were used to establish the SNI models by resecting 10 mm of right sciatic nerve.The rats in model group received no further treatment,while the rats in AS group and ADSC+AS group were bridged with AS and the constructed tissue-engineered nerve at the two ends of the injured nerve,respectively.At 6 weeks after surgery,transmission electron microscope was used to observe the ultrastructure of dorsal root ganglion of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of CNTF,p-JAK2,and p-STAT3 in dorsal root ganglion of the rats;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of CNTF,JAK2,and STAT3 in dorsal root ganglion of the rats in various groups.Results:After 7 d of primary ADSC culture,a large number of large and long spindle-shaped cells were observed under the inverted microscope,arranged in clusters or whirlpools;red lipid droplets were observed with oil red O staining under microscope,and calcified nodules were observed with Alizarin red staining under microscope,indicating that the isolated and cultured cells had multidirectional differentiation ability.Compared with normal nerve tissue,the level of DNA in AS of rats was significantly decreased(P<0.05).Compared with control group,the nuclear membrane of dorsal root ganglion cells in model group was uneven and serrated,the number of organelles in the cytoplasm was decreased,mitochondria were swollen with broken or missing cristae and unclear structure;the CNTF protein and mRNA expression levels were significantly decreased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly increased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly increased(P<0.01).Compared with model group,the serrated change of nuclear membrane of the dorsal root ganglion cells in AS group was significantly alleviated,the number of organelles in the cytoplasm was increased,and mitochondrial swelling was reduced;in ADSC+AS group,the nuclear membrane of dorsal root ganglion cells tended to be intact,the number of organelles was increased,and mitochondrial swelling and vacuolization were significantly reduced;the CNTF protein and mRNA expression levels in the dorsal root ganglion in AS group and ADSC+AS group were significantly increased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Compared with AS group,the CNTF protein and mRNA expression levels in ADSC+AS group were significantly increased(P<0.05 or P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Conclusion:The application of ADSC combined with AS can improve the ultrastructure of dorsal root ganglion in the SNI rats,and the mechanism may be related to the increased CNTF expression and decreased activation of the JAK2/STAT3 signaling pathway in the dorsal root ganglion by ADSC combined with AS application.

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.