Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis(UC).Methods Acer1 knockout mice(Acer1 KO)were constructed,and the UC model was induced by continuous drinking water of sodium dextran sulfate(DSS)for 7 days,and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared.The expression levels of intestinal mucosal barriers(ZO-1,Occludin,Claudin,JAMA)were detected by RT-PCR and immunohistochemistry.Systemic immune response levels(IL-1b、IL-6、IL-23、IL-17、IL-10,and TNF-a)were assessed by ELISA and intestinal inflammatory infiltration levels(TNF-a、IL-1b、IL-6、IL-17、IL-21,etc.)were assessed by RT-PCR.Results There was no significant difference between C57 and Acer1 KO mice in free drinking water.In the DSS induced UC model,compared with C57 mice,the survival rate of Acer1 KO mice decreased,the weight decreased significantly,the mechanical barrier and mucus barrier protein expression levels decreased significantly,the intes-tinal epithelial barrier was seriously damaged,the inflammatory response was strong,and the cytokine infiltration was obvious,with statistical differences(P<0.05).Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier,preventing endotoxin,and delaying the progression of UC.

OBJECTIVES: To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia. METHODS: Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining. RESULTS: Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention. CONCLUSIONS In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.
Animals ; Electroacupuncture ; Astrocytes/cytology* ; Cell Transdifferentiation ; Male ; Mice, Inbred C57BL ; Brain Ischemia/physiopathology* ; Mice ; Neurons/cytology* ; Doublecortin Protein

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

Objective To investigate the therapeutic effect of folic acid combined with decitabine in diabetic retinop-athy(DR)mice with different methylenetetrahydrofolate reductase(MTHFR)genotypes.Methods The DR model mice were created by mating 20 MTHFR-/-mice with 20 wild-type C57 mice.A random number table method was employed to allocate 20 successfully modelled mice into the model group,DAC group,FA group,and FA+DAC group,with five mice assigned to each group.Five untreated MTHFR-/-and wild-type mice served as normal control.After constructing the DR model,the DAC group was injected intraperitoneally with 0.25 mg·kg-1 decitabine once every 5 days;the FA group was given 70 μg·kg-1 folic acid by tube feed once a day;the FA+DAC group was given 0.25 mg·kg-1 decitabine and 70μg·kg-1 folic acid at the same time;and the normal group was given an equal amount of physiological saline.All of the above groups were intervened for 30 days.OCT was employed for the measurement of retinal thickness,OCTA for retinal vascular density,histopathology(HE staining)for pathological changes in the mouse retina,real-time fluorescence quanti-tative PCR for mRNA expression,and Western blot analysis for protein expression levels.Results Compared with the wild-type model group,the degree of increase in retinal thickness and vascular density in the retinal layer was more pro-nounced in the MTHFR-/-mice model group(all P＜0.05).In wild-type mice,retinal thickness and retinal layer vessel den-sity were reduced in the DAC,FA and FA+DAC groups compared to the model group,with the FA+DAC group show-ing the greatest degree of reduction.The differences were all statistically significant(all P＜0.05);In MTHFR-/-mice,reti-nal thickness and vascular density in the retinal layer were reduced in the DAC group and the FA+DAC group compared to the model group(allP＜0.05).HE staining results showed an increased extent of retinal damage in the MTHFR-/-mice model group compared with the wild-type mice model group.Compared with the model group,the DAC group and the FA+DAC group had thinner retinas and more aligned ganglion cell layers in all types of mice,with the FA group having a worse effect and the FA+DAC group having a better treatment effect.The results of the polymerase chain reaction(PCR)revealed that the relative expression of the SAHH,MAT2A and DNMT1 proteins in the retinal tissues of the wildtype and MTHFR-/-mice model groups was elevated in comparison to the control group(all P＜0.05).Furthermore,the relative mR-NA expression of the DAC,FA and FA+DAC groups was reduced in comparison to the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein mRNA was decreased in the model group compared with the con-trol group,and increased in the DAC group,FA group,and FA+DAC group compared with the model group(all P＜0.05).Western blot results showed that the relative expression of DNMT1,MAT2A and SAHH proteins in the retinal tissues of the wild-type and MTHFR-/-mice model groups was higher than that of the control group(all P＜0.05),and the relative expression was lower in the DAC,FA,and FA+DAC groups compared with that in the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein in the retinal tissue of the model group was lower than that of the control group,and the relative expression of MTHFR protein in the FA group and the FA+DAC group was elevated com-pared with that of the model group(all P＜0.05).Conclusion The protective effect of folic acid combined with decit-abine on DR was superior to that of decitabine alone;treatment with folic acid in combination with decitabine may have yielded better efficacy in wild-type DR mice.

Objective To investigate the therapeutic effect of folic acid combined with decitabine in diabetic retinop-athy(DR)mice with different methylenetetrahydrofolate reductase(MTHFR)genotypes.Methods The DR model mice were created by mating 20 MTHFR-/-mice with 20 wild-type C57 mice.A random number table method was employed to allocate 20 successfully modelled mice into the model group,DAC group,FA group,and FA+DAC group,with five mice assigned to each group.Five untreated MTHFR-/-and wild-type mice served as normal control.After constructing the DR model,the DAC group was injected intraperitoneally with 0.25 mg·kg-1 decitabine once every 5 days;the FA group was given 70 μg·kg-1 folic acid by tube feed once a day;the FA+DAC group was given 0.25 mg·kg-1 decitabine and 70μg·kg-1 folic acid at the same time;and the normal group was given an equal amount of physiological saline.All of the above groups were intervened for 30 days.OCT was employed for the measurement of retinal thickness,OCTA for retinal vascular density,histopathology(HE staining)for pathological changes in the mouse retina,real-time fluorescence quanti-tative PCR for mRNA expression,and Western blot analysis for protein expression levels.Results Compared with the wild-type model group,the degree of increase in retinal thickness and vascular density in the retinal layer was more pro-nounced in the MTHFR-/-mice model group(all P＜0.05).In wild-type mice,retinal thickness and retinal layer vessel den-sity were reduced in the DAC,FA and FA+DAC groups compared to the model group,with the FA+DAC group show-ing the greatest degree of reduction.The differences were all statistically significant(all P＜0.05);In MTHFR-/-mice,reti-nal thickness and vascular density in the retinal layer were reduced in the DAC group and the FA+DAC group compared to the model group(allP＜0.05).HE staining results showed an increased extent of retinal damage in the MTHFR-/-mice model group compared with the wild-type mice model group.Compared with the model group,the DAC group and the FA+DAC group had thinner retinas and more aligned ganglion cell layers in all types of mice,with the FA group having a worse effect and the FA+DAC group having a better treatment effect.The results of the polymerase chain reaction(PCR)revealed that the relative expression of the SAHH,MAT2A and DNMT1 proteins in the retinal tissues of the wildtype and MTHFR-/-mice model groups was elevated in comparison to the control group(all P＜0.05).Furthermore,the relative mR-NA expression of the DAC,FA and FA+DAC groups was reduced in comparison to the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein mRNA was decreased in the model group compared with the con-trol group,and increased in the DAC group,FA group,and FA+DAC group compared with the model group(all P＜0.05).Western blot results showed that the relative expression of DNMT1,MAT2A and SAHH proteins in the retinal tissues of the wild-type and MTHFR-/-mice model groups was higher than that of the control group(all P＜0.05),and the relative expression was lower in the DAC,FA,and FA+DAC groups compared with that in the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein in the retinal tissue of the model group was lower than that of the control group,and the relative expression of MTHFR protein in the FA group and the FA+DAC group was elevated com-pared with that of the model group(all P＜0.05).Conclusion The protective effect of folic acid combined with decit-abine on DR was superior to that of decitabine alone;treatment with folic acid in combination with decitabine may have yielded better efficacy in wild-type DR mice.

Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis(UC).Methods Acer1 knockout mice(Acer1 KO)were constructed,and the UC model was induced by continuous drinking water of sodium dextran sulfate(DSS)for 7 days,and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared.The expression levels of intestinal mucosal barriers(ZO-1,Occludin,Claudin,JAMA)were detected by RT-PCR and immunohistochemistry.Systemic immune response levels(IL-1b、IL-6、IL-23、IL-17、IL-10,and TNF-a)were assessed by ELISA and intestinal inflammatory infiltration levels(TNF-a、IL-1b、IL-6、IL-17、IL-21,etc.)were assessed by RT-PCR.Results There was no significant difference between C57 and Acer1 KO mice in free drinking water.In the DSS induced UC model,compared with C57 mice,the survival rate of Acer1 KO mice decreased,the weight decreased significantly,the mechanical barrier and mucus barrier protein expression levels decreased significantly,the intes-tinal epithelial barrier was seriously damaged,the inflammatory response was strong,and the cytokine infiltration was obvious,with statistical differences(P<0.05).Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier,preventing endotoxin,and delaying the progression of UC.

Objective:To investigate the correlation between vitamin D levels and thyroid hormone sensitivity in euthyroid individuals.Methods:This cross-sectional study included 5 894 euthyroid individuals who underwent health examinations at the Department of Health Management, Peking Union Medical College Hospital, from December 2023 to February 2024. Thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotroph thyroxine resistance index (TT4RI), and the ratio of free triiodothyronine (FT3)/free thyroxine (FT4) were calculated to assess thyroid hormone sensitivity. Participants were categorized into vitamin D deficiency and non-deficiency groups based on serum 25(OH)D levels. The differences in thyroid hormone sensitivity indices and other clinical characteristics between the two groups were compared. Multivariate logistic regression models were used to analyze the association between vitamin D levels and thyroid hormone sensitivity, and stratified analysis was conducted to explore the association in different genders.Results:Among the study participants, 4 731 (80.3%) had vitamin D deficiency. Compared with the non-deficient group, the deficient group had a lower TFQI (-0.03(-0.31, 0.23) and -0.01(-0.28, 0.27)) ( Z=-2.130, P=0.033) and a higher FT3/FT4 ratio ((0.36±0.04) and (0.35±0.04)) ( t=-4.592, P<0.001). After adjusting for confounding factors including gender and age, the risk of impaired central and peripheral thyroid hormone sensitivity significantly increased in the non-deficient group (TFQI ( OR=1.16, 95% CI: 1.01-1.34); FT3/FT4 ( OR=1.23, 95% CI: 1.05-1.45)) (all, P<0.05). Conclusion:In euthyroid individuals, people with higher vitamin D levels have a higher risk of impaired thyroid hormone sensitivity.

Objective:To investigate the correlation between vitamin D levels and thyroid hormone sensitivity in euthyroid individuals.Methods:This cross-sectional study included 5 894 euthyroid individuals who underwent health examinations at the Department of Health Management, Peking Union Medical College Hospital, from December 2023 to February 2024. Thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotroph thyroxine resistance index (TT4RI), and the ratio of free triiodothyronine (FT3)/free thyroxine (FT4) were calculated to assess thyroid hormone sensitivity. Participants were categorized into vitamin D deficiency and non-deficiency groups based on serum 25(OH)D levels. The differences in thyroid hormone sensitivity indices and other clinical characteristics between the two groups were compared. Multivariate logistic regression models were used to analyze the association between vitamin D levels and thyroid hormone sensitivity, and stratified analysis was conducted to explore the association in different genders.Results:Among the study participants, 4 731 (80.3%) had vitamin D deficiency. Compared with the non-deficient group, the deficient group had a lower TFQI (-0.03(-0.31, 0.23) and -0.01(-0.28, 0.27)) ( Z=-2.130, P=0.033) and a higher FT3/FT4 ratio ((0.36±0.04) and (0.35±0.04)) ( t=-4.592, P<0.001). After adjusting for confounding factors including gender and age, the risk of impaired central and peripheral thyroid hormone sensitivity significantly increased in the non-deficient group (TFQI ( OR=1.16, 95% CI: 1.01-1.34); FT3/FT4 ( OR=1.23, 95% CI: 1.05-1.45)) (all, P<0.05). Conclusion:In euthyroid individuals, people with higher vitamin D levels have a higher risk of impaired thyroid hormone sensitivity.

Objective To observe the effect of oxycodone hydrochloride combined with parecoxib sodium preemptive analgesia on postoperative pain in patients undergoing gynecologic laparoscopic surgery.Methods The clinical data of patients who underwent gynecological laparoscopic surgery at the General Hospital of Huainan Oriental Hospital Group from July 2021 to February 2023 were retrospectively analyzed and the patients were divided into a control group(parecoxib sodium)and a combined group(oxycodone hydrochloride combined with parecoxib sodium)according to the different preemptive analgesic regimens.The observational indexes of this study included opioid consumption within 24 h postoperatively,visual analog scale(VAS)scores at 0,2,6,12 and 24 h postoperatively,the number of effective presses of the patient controlled analgesiac(PCA),the time of the first press of the PCA,the number of remedial analgesia,the satisfaction of analgesia,and the occurrence of postoperative adverse reactions.Results A total of 80 patients were included in the study,with 39 in the control group and 41 in the combined group.The time of the first press of the analgesic pump was significantly longer in the combined group than in the control group(P＜0.05),while the number of effective presses and sufentanil consumption were significantly lower in the combined group than in the control group(P＜0.05).The difference in the number of remedial analgesia between the two groups was not statistically significant(P＞0.05).The VAS scores at 0 h,2 h and 6 h postoperatively in the combined group were significantly lower than those in the control group(P＜0.05),and the differences between the VAS scores at 12 h and 24 h postoperatively were not statistically significant(P＞0.05).The analgesic satisfaction score of patients in the combined group was significantly higher than that of the control group(P＜0.05),and the difference in the incidence of adverse reactions was not statistically significant(P＞0.05).Conclusion The preemptive analgesia regimen of oxycodone hydrochloride combined with parecoxib sodium significantly reduced the consumption of opioid drugs in patients after gynecological laparoscopic surgery,alleviated postoperative pain,and improved patient satisfaction.

Gastroesophageal reflux related cough is located in the lung and stomach.The basic pathogenesis is the inversion of stomach qi and the lung loss propagating and descending.In view of the above,based on the theory of"relevance of lung and stomach",this article analyzed the modern mechanism of"relevance of lung and stomach"in gastroesophageal reflux related cough,which included"microinhalation"theory,"esophagus-bronchial reflex"theory,and"airway neurogenic inflammation"theory.This article also put forward the TCM disease name of"gastric cough",and the treatment methods of"simultaneous treatment of lung and stomach"and"treatment of cough from stomach",which would provide new ideas for the theoretical and mechanism research of TCM treatment of gastroesophageal reflux related cough.