Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective:To investigate the impacts and mechanisms of the GCH1-S81A mutants of the rate-limiting enzyme GTP cyclohydrolase 1 (GCH1) at key phosphorylation sites on the radiosensitivity of esophageal cancers during the de novo synthesis of tetrahydrobiopterin (BH4). Methods:The KYSE-150 cell lines of esophageal squamous cell carcinoma with stable GCH1 overexpression at different phosphorylation levels were constructed in this study. Based on GCH1′s phosphorylation levels and radiation doses, the experimental groups were divided into the blank control group, the empty virus group, the empty virus + irradiation group, the wild-type GCH1 group, the GCH1 phosphorylation group, the GCH1 dephosphorylation group, the GCH1 dephosphorylation + irradiation group, the validation group, and the validation + irradiation group. The Western blot and the CCK-8 assay were employed to detect the infection efficiency and the survival rates of tumor cells in various groups, respectively. The flow cytometry was applied to detect the changes in the apoptosis rate, reactive oxygen species (ROS) level, and lipid peroxide level of tumor cells in various groups. The colony formation assay was used to detect the changes in the radiosensitivity of tumor cells. Besides, the Western blot was performed to detect the changes in the expression of ferroptosis-related proteins.Results:The GCH1 dephosphorylation group showed a significantly decreased expression level of phosphorylated GCH1-S81 protein in the cells at 48 h after infection ( t=9.35, 16.57, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group exhibited a significantly decreased cell survival rate 24 h after 10 Gy X-ray irradiation ( t=26.97, P<0.05). The ROS levels in KYSE-150 cells at 8 h after 10 Gy X-ray irradiation, and the apoptosis rates and lipid peroxide levels at 48 h after irradiation, all showed a significant increase ( t=17.89-131.1, P<0.05), which was further aggravated following the addition of GCH1-S81A mutants ( t=157.06-97.81, P<0.05). This phenomenon could be inhibited by complementing wild-type GCH1 ( t=66.38-23.08, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group manifested decreased colony formation capacity under various X-ray doses (2, 4, 6 and 8 Gy, t=7.31-8.16, P<0.05). The GCH1-S81A mutation reduced the expression level of the ferroptosis-related protein GPX4 ( t=4.55, P<0.05), which was further decreased after 10 Gy X-ray irradiation ( t=12.98, P<0.05). Conclusions:The GCH1-S81A dephosphorylated mutants can inhibit the growth of esophageal carcinoma cells KYSE-150 and enhance their radiosensitivity, which may hold promise as a novel approach to improve the efficacy of radiotherapy for esophageal cancers.

Objective To observe the effect of intelligent flexible ankle stretching training on lower extremity spasm in patients with spinal cord injury. Methods From June,2021 to May,2024,28 patients with spinal cord injury were randomly divided into control group(n=14)and experimental group(n=14).Both groups received conventional rehabilitation treatment.On this ba-sis,the control group received manual extension treatment,and the experimental group received intelligent flexi-ble ankle stretching system training,for eight weeks.The modified Ashworth Scale(MAS),ankle dorsiflexion an-gle,Clinical Spasticity Index(CSI),max root mean square(RMSmax)of surface electromyography of gastrocne-mius medial head and vibration perception threshold(VPT)of great toe were compared. Results After treatment,MAS(χ2=10.378,P=0.035),ankle dorsiflexion angle(Z=-3.306,P<0.001),CSI(t=4.101,P=0.001)and RMSmax of gastrocnemius medial head(Z=-3.296,P<0.001)improved in the experimental group,while MAS(χ2=11.418,P=0.022),ankle dorsiflexion angle(Z=-1.986,P=0.047)and RMSmax of gas-trocnemius medial head(Z=-2.297,P=0.021)were better in the experimental group than in the control group.Although VPT was improved after treatment,no significant difference was found within and beteen groups(P>0.05). Conclusion The intelligent flexible ankle stretching training could improve the lower limb muscle spasticity in patients with spinal cord injury,and may be benefit for foot proprioception.

Objective Radioactive intestinal injury is a common complication during radiotherapy of tumors.The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells.Methods A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession.The bile acids were quantified using metabolomics analysis.IEC-6 cells,a small intestinal epithelial cell line,were divided into a dimethyl sulfoxide(DMSO)control group receiving DMSO and 0 Gy irradiation,a glycoursodeoxycholic acid(GUDCA)experimental group receiving GUDCA and 0 Gy irradiation,a DMSO irradiation group receiving DMSO and 10 Gy irradiation,and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation.Cell viability and cytotoxicity was assessed by CCK-8 assay test.The apoptosis rate of cells was determined by flow cytometry.The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media.The expression levels of proteins associated with cell death were determined using Western blot.Results After exposure to irradiation,the small intestine tissues of the rats showed typical radioactive intestinal injury.In addition,various bile acids showed fluctuation before and after irradiation.Among the bile acids,GUDCA increased significantly at 3 d after irradiation,but returned to the pre-irradiation level at 7 d after irradiation.Compared with the control group,after GUDCA treatment at 20 μmol/L for 24 h,the cell viability rate after irradiation was significantly higher than that of the DMSO group(P＜0.05);the expression levels of the proteins,including PARP,caspase-3,RIP,and GSDMD,were significantly lower than those in the control group(P＜0.05).After GUDCA treatment at 20 μmol/L for 24 h and 48 h,the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group(P＜0.05).Compared with the DMSO control group,the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0,2,4,and 6 Gy(P＜0.05).D0,or the mean lethal dose,of the GUDCA group was 6.374,while that of the DMSO group was 4.572.Compared with the DMSO control group,the D0 value of the GUDCA treatment group increased,and the sensitization enhancement ratio(SER)was 0.717.Conclusion After exposing the abdomen of rats to irradiation,the intestinal bile acid metabolism of the rats will change significantly,and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

Objective:To explore vibration, position and motion proprioception of the ankle joints after a stroke.Methods:Twenty-eight stroke survivors with impaired ankle proprioception were divided into a right-side stroke group ( n=18) and a left-side stroke group ( n=8). Twenty-two healthy volunteers constituted a control group. Vibration perception thresholds, passive and active joint angle resetting, and motion minimum thresholds were quantified among the stroke survivors on both the healthy and the affected side. With the controls the dominant and non-dominant sides were used. The differences in proprioception between the healthy volunteers and the stroke patients, between the affected side and the healthy side of the stroke patients, and between left- and right-side stroke patients were analyzed and compared. Results:Among the stroke survivors the vibration perception threshold on the affected side averaged (28.91±22.53)μm. The absolute difference in the perception of passive positioning was (5.49±5.39)° for 15° of plantar flexion and (4.48±3.89)° for 5° of dorsal extension. In active positioning plantar flexion was (5.23±4.34)° and for 30° of plantar flexion it was (3.26±1.73)°. The 5° dorsal extension error was (4.97±3.48)°. The motion perception thresholds between 20° of plantar flexion, 10° of plantar flexion and the neutral position were significantly higher, on average, than among the control group. The stroke group also had significantly higher motion perception thresholds than the control group.Conclusion:The vibration, position, and motion sense of the ankle joint on a stroke survivor′s affected side tend to be impaired, with the impairment of vibration and motion sensing tend to be more substantial. After stroke, there is also mild impairment of vibration, position and motion sensing in the healthy ankle joint. The impairment of proprioception caused by right cerebral hemisphere injury may be more serious than that caused by injury on the left.

Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

When the coverage of the vaccinated people reaches a certain percentage of the population, the herd protection will protect the unvaccinated persons. However, the traditional clinical evaluation of vaccines performing individual randomized design fails to evaluate the herd protection of vaccines. Compared with the individual randomized design, the cluster-randomized design can determine the overall protection by the vaccine more comprehensively. It has become increasingly common to perform a cluster-randomized design in clinical trials of vaccines in Phase Ⅲ and Ⅳ clinical trials. However, little is known about the application of cluster randomized design in vaccine clinical trials in China. We, at this moment, do a review of the application of random cluster design in vaccine clinical trials and provide references for future research in China.

OBJECTIVE: To investigate the effect of short-term rehabilitation therapy based on exercise on lung function in coal workers' with pneumoconiosis(CWP). METHODS: A total of 74 CWP patients were divided into control group(32) and treatment group(42) by random number table method. The control group received routine treatment only. The treatment group underwent 6 months of exercise-based rehabilitation treatment on the basis of routine treatment. The lung function was assessed in two groups to evaluate the treatment efficacy. RESULTS: Before rehabilitation treatment, the vital capacity(VC) and forced vital capacity(FVC) of patients in the treatment group were lower than that in the control group(P<0.05). But there was no significant difference in forced expiratory volume in first second(FEV_(1.0)) and FEV_(1.0)% between the two groups(P>0.05). After treatment, VC and FVC in the treatment group were higher than that before treatment in the same group(P<0.05). However, there was no significant difference in the four lung function indexes before and after treatment in the control group(P>0.05). The difference of VC and FVC before and after treatment in the treatment group was higher than those in the control group(P<0.01). However, there was no significant difference in FEV_(1.0 )and FEV_(1.0)% between the two groups before and after treatment(P>0.05). CONCLUSION: Exercise-based short-term rehabilitation therapy can improve lung ventilation of CWP patients.