The intestine is the largest immune and metabolic site in the body and is thus important for animal health.The integrity of the mucosal barrier and function are fundamental factors protecting the health of the intestine.Stress has been reported to have profound effects on the gastrointestinal tract,including altering gut permeability,the intestinal barrier,and homeostasis.Tryptophan is a functional essential amino acid that alters the gut microbiota and regulates intestine structural and functional change,thus contributing to host physiology and metabolism.Changes in tryptophan metabolism and its metabolites in brain and intestinal tissues during stress suggest that tryptophan may play an important role in the stress response.We therefore review the literature on the mechanisms underlying stress-related diseases and the role of tryptophan metabolism in the regulation of gut homeostasis,with particular focus on functional bowel disorders and their relationship to stress,to provide a theoretical foundation for targeting tryptophan in stress-related intestine diseases.

Objective Given that psychosocial stress can contribute to a series of diseases,such as inflammatory bowel disease and irritable bowel syndrome,we aimed to establish an experimental chronic restraint mouse intestinal stress injury model as a basis for exploring the pathogenic mechanism of chronic restraint stress-induced gastrointestinal diseases,and for developing preventive and curative measures.Methods Eighteen male SPF-grade BALB/c mice were acclimatized for 7 days and then divided into a control group and a chronic restraint stress group according to body weight,using a randomized numerical table method.The mice were subjected to restraint stress for 3 hours per day for 14 days to establish an intestinal injury model.The model was evaluated by observing body weight,pathological changes in intestinal histomorphology,expression of tight junction proteins,apoptosis of intestinal epithelial cells,and mRNA expression levels of inflammatory cytokines.Results After 14 days of chronic restraint stress,model mice showed weight loss,shortened duodenal villus height,abnormal crypt structure,a decreased villus/crypt ratio,colonic mucosal inflammatory cell infiltration,and irregular crypt structure.Protein immunoblotting,immunohistochemistry,and immunofluorescence staining showed that the expression levels of the duodenal and colonic tight junction proteins Occludin and Claudin-1 were significantly decreased in mice after chronic restraint stress(P＜0.05),while expression levels of the apoptotic protein cleaved-caspase-3 in intestinal epithelial cells were significantly increased(P＜0.05).Regarding the mRNA expression levels of intestinal inflammatory factors and chemokines,chronic restraint stress for 14 days significantly increased the gene expression levels of interleukin(IL)-1β,IL-6,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α,and IL-10 in the duodenum of mice(P＜0.05),and significantly increased the gene expression levels ofIL-1β,IL-6,and MCP-1 in the colon(P＜0.001).Conclusions The use of a behavioral restriction device to restrain mice continuously for 14 days led to abnormal intestinal tissue structure,intestinal barrier dysfunction,and intestinal epithelial cell apoptosis,and triggered an intestinal inflammatory response in the stressed mice,indicating successful establishment of a mouse model of intestinal injury by chronic restraint stress.

Objective By simulating acute hypoxic conditions, an experimental model of intestinal stress injury in plateau mice was established to explore the pathogenic mechanism of acute gastrointestinal diseases in plateau, and to lay foundation for preventive and therapeutic measures.MethodsThirty-six SPF-grade adult male BALB/c mice were randomly divided into four groups: normoxic 24 h, normoxic 72 h, hypoxic 24 h, and hypoxic 72 h, based on body weight using a randomized numerical table method, with nine mice in each group. Mice in the normoxic group were kept in a conventional barrier environment, while those in the hypoxic group were placed in a hypoxic chamber within the barrier environment with oxygen concentration set at 10% to simulate plateau conditions. They were subjected to stress for 24 h and 72 h, respectively, in order to establish a model of intestinal injury induced by acute hypoxia. After modeling, the mice were weighed, anesthetized with 1% pentobarbital sodium, and then euthanized by cervical dislocation. Duodenal and colonic tissues were collected. Histopathological morphology of intestinal tissues was observed after HE staining. Western blotting and immunohistochemistry were used to detect the expression levels of tight junction-related proteins in intestinal tissues. Real-time fluorescence quantitative PCR was performed to measure the expression levels of inflammatory cytokines and chemokines. TUNEL staining was used to assess apoptotic activity of intestinal epithelial cells, thus evaluating intestinal injury-related phenotypes in this model.Results Compared with the normoxic groups, mice in the 24 h and 72 h hypoxia groups showed weight loss, shortened duodenal villi, abnormal crypt structure, and decreased villus/crypt ratio. The colonic mucosa was infiltrated with inflammatory cells and irregular crypt structure. Expression levels of Occludin and zonula occludens-1 (ZO-1) were significantly decreased in duodenal and colonic tissues of mice in the 24 h and 72 h hypoxia groups (P<0.05). The expression of pro-apoptotic protein Bax was significantly up-regulated while expression of anti-apoptotic protein Bcl-2 was significantly down-regulated in duodenal tissues (P<0.05). Apoptotic activity of intestinal epithelial cells was significantly enhanced (P<0.05). In addition, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) mRNA levels were significantly increased in duodenal tissues after 24 and 72 h of hypoxic stress(P<0.05). After 24 h of hypoxic stress, there was no significant change in the expression levels of inflammatory cytokines in colon tissues (P>0.05), but after 72 h, the expression levels of pro-inflammatory factors IL-1β, TNF-α, IL-6, MCP-1, and anti-inflammatory factor IL-10 mRNAs significantly increased in colon tissues of mice (P<0.05).Conclusion The usage of a hypoxia chamber to simulate an acute hypoxic environment in plateau can lead to abnormal intestinal tissue structure, intestinal barrier dysfunction, and induce intestinal epithelial cell apoptosis, triggering an intestinal inflammatory response in stress mice. These findings indicate the successful construction of a mouse model for an acute hypoxic stress-induced intestinal injury.

Objective To investigate the application value of the global myocardial work parameters in the non-invasive pressure-strain loop (PSL) technology for early assessment of left ventricular systolic function in patients with chronic kidney disease (CKD). Methods A retrospective analysis was performed on 74 patients with normal left ventricular ejection fraction (LVEF) who were hospitalized in the Nephrology Department of Zhongshan Hospital (Xiamen Branch), Fudan University, from August 2021 to December 2021. Based on CKD stages, patients were divided into early group (CKD stages 1-3) and advanced group (CKD stages 4-5). Additionally, 30 healthy volunteers matched for age and gender were selected as the control group. General clinical data, routine left ventricular ultrasound indicators, myocardial strain, and global myocardial work parameters were collected and compared among the three groups. Correlation analysis and multiple linear regression were used to assess the influencing factors of myocardial work. Results There were no statistically significant differences in global work index (GWI) and global constructive work (GCW) among the three groups. Compared to the control group, both CKD groups showed significantly reduced global work efficiency (GWE), along with significantly increased global waste work (GWW, P＜0.05). The absolute value of global longitudinal strain (GLS) in the advanced CKD group (n＝42) was significantly lower than that in the early CKD group (n＝32; [﹣17.09±0.82]% vs [﹣18.33±0.90]%, P＜0.05), and GWE was also significantly lower (93.00%[90.00%, 95.00%] vs 96.00%[92.25%, 96.75%], P＜0.05), while GWW was significantly higher than that in the early CKD group (150.00 mmHg%[105.25 mmHg%, 215.00 mmHg%] vs 88.00 mmHg%[64.25 mmHg%, 144.50 mmHg%], P＜0.05). Correlation analysis showed that GWE was negatively correlated with the absolute value of GLS and peak strain dispersion (PSD; r＝﹣0.396, ﹣0.558, P＜0.05), GWW was positively correlated with absolute value of GLS, and PSD (r＝0.341, 0.610, P＜0.01). Multiple linear regression results indicated that PSD was an independent influencing factor for GWE (β＝﹣0.558, P＜0.001) and GWW (β＝0.538, P＜0.001). Conclusions The myocardial work parameters GWE and GWW in non-invasive left ventricular PSL technology can identify subclinical left ventricular systolic dysfunction in patients with CKD early and quantitatively.

Objective:To explore the prognostic predictive value of detecting minimal residual disease (MRD) after 2 courses of hypomethylating agents (HMA) combined with low-dose induction chemotherapy in patients with acute myeloid leukemia (AML).Methods:The data of 43 newly diagnosed AML patients treated by HMA combined with low-dose induction chemotherapy in Jingjiang People's Hospital of Jiangsu Province from January 2016 to January 2021 were retrospectively analyzed, and the bone marrow MRD levels were detected by multiparametric 10-color flow cytometry (MFC) after 1 course and 2 courses of chemotherapy. Patients were divided into three groups according to MRD levels: the group with negative MRD after 1 course of induction chemotherapy (MRD-1 group), the group with negative MRD after 2 courses of induction chemotherapy (MRD-2 group), and the group without negative MRD after 2 courses of induction chemotherapy (MRD+ group). Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves of all patients and each group, and log-rank test was performed to compare them; the influencing factors for OS were analyzed using univariate and multivariate Cox proportional hazards models.Results:Among the 43 patients, 17 patients (39.5%) were in the MRD-1 group, 14 patients (32.6%) were in the MRD-2 group, and 12 patients (27.9%) were in the MRD+ group. There were no statistical differences among the 3 groups in gender, age, hemoglobin level at initial diagnosis, white blood cell count, platelet count, lactate dehydrogenase level, disease subtype, WT1 expression, karyotype, and genetic risk stratification (all P > 0.05). The median follow-up was 15 months (1-67 months). Survival analysis showed a median OS time of 21 months (95% CI 15 months -not reached) in 43 patients and a median PFS time of 12 months (95% CI 9-18 months) in 29 patients included in the PFS analysis; PFS and OS in the MRD-1 and MRD-2 groups were better than those in the MRD+ group (all P < 0.01), and the differences in PFS and OS between the MRD-1 and MRD-2 groups were not statistically significant (both P > 0.05); the median PFS time was 5 months (95% CI 2 months-not reached) in the MRD+ group, the median PFS time was 15 months (95% CI 7 months-not reached) in the MRD-1 group, and the median PFS time was 18 months (95% CI 11 months-not reached) in the MRD-2 group; the median OS time in the MRD+ group was 9 months (95% CI 7 months-not reached), the median OS time was not reached in the MRD-1 group, and the median OS time was 38 months (95% CI 38 months-not reached) in the MRD-2 group. Multivariate Cox regression analysis showed that age ( HR = 1.080, 95% CI 1.004-1.160, P = 0.038), MRD status (MRD-1 vs. MRD+: HR = 0.125, 95% CI 0.031-0.507, P = 0.004; MRD-2 vs. MRD+: HR = 0.146, 95% CI 0.037-0.577, P = 0.006) were independent influencing factors for OS in AML patients. Conclusions:The survival is good in AML patients with MRD negative conversion after both 1 course and 2 courses of HMA combined with low-dose induction chemotherapy, and both are better than that in patients with positive MRD after 2 courses of chemotherapy.

Objective To analyze the changes of postoperative pulmonary function in lung transplant recipients. Methods Clinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. Results Postoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity (FVC) to predicted value ratio (FVC%pred), forced expiratory volume in one second (FEV₁) to predicted value ratio (FEV₁%pred), FEV₁/FVC to predicted value ratio (FEV₁/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (D_LCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV₁%pred were gradually increased within postoperative 9 months, and D_LCOc%pred was gradually elevated within postoperative 3 months (all P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV₁%pred≥80% in 41 cases, FEV₁/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 case and FEV₁%pred≤40% in 1 case, respectively. Sixteen recipients had D_LCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (D_LCOc/V_A%pred) ≥80% in 63 cases, D_LCOc%pred≤40% in 4 cases and D_LCOc/V_A%pred≤40% in 1 case, respectively. Postoperative FVC%pred, FEV₁/FVC%pred and D_LCOc%pred in recipients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative D_LCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). Conclusions Pulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.

Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Humans ; Hypoparathyroidism/genetics* ; Infant, Newborn ; Kidney/abnormalities* ; Male ; Syndrome ; Urogenital Abnormalities/genetics*

Objective:To understand the reserves of wild resources and artificial cultivation of Curcuma aromatica Salisb. in Guangxi, so as to provide basis for the conservation, rational development and utilization of germplasm resources of Curcuma aromatica Salisb. in Guangxi. Methods:By using literature retrieval and field investigation methods to analyze of geographic distribution, growing environment and community of Curcuma aromatica Salisb. in Guangxi. Results:Wild Curcuma aromatica Salisb. has strong adaptability and is growing in limestone mountains, earthen hills and plains. It usually grows at the foot of mountains or the edge of gullies or on the farmland or along the roads. It has a strong adaptability to altitude, soil type. The habitat of wild Curcuma aromatica Salisb. has been destroyed by human reclamation. Conclusion:The geographical distribution, growing environment and community of wild resources of Curcuma aromatica Salisb. in Guangxi were known, which provids the reference for the conservation, development and utilization of Curcuma aromatica Salisb.

OB JECTIVE To study the anti-inflammatory effect of couplet medicinals of Achyranthes bidentata -Eucommia ulmoides. METHODS Mouse macrophage RAW 264.7 were divided into blank group ，model group ，A. bidentata group（800 μg/mL），E. ulmoides group（800 μg/mL）and low- ，medium- and high- concentration groups of couplet medicinals of A. bidentata - E. ulmoides （400，800，1 600 μg/mL）. Excep for blank group and model group ，the other groups were added with corresponding drugs for 6 hours；then blank group was continued to add into the medium ，while model group was added into 10 μg/mL lipopolysaccharide （to induce the inflammatory model ）；other groups were added into corresponding drugs and 10 μ g/mL lipopolysaccharide. The levels of inflammatory factors [nitric oxide （NO），interleukin-1β（IL-1β），IL-6，tumor necrosis factor-α （TNF-α）] were detected ，and Jin ’s formula was used to evaluate the effects of A. bidentata -E. ulmoides . The expression of inducible nitric oxide synthase （iNOS），cyclooxygenase-2（COX-2），nuclear factor kappa-B （NF-κB）and inhibitor α of NF-κB （IκBα）as well as the phosphorylation of NF-κB p65，IκB kinase（IKK），p38 mitogen-activated protein kinase （p38 MAPK）， extracellular signal-regulated kinase （ERK）and c-Jun N-terminal kinase （JNK）were determined. RESULTS Compared with blank group，the level of inflammatory factors ，protein expression of iNOS and COX- 2 as well as the phosphorylation of NF-κB p65， IKK，p38 MAPK，ERK and JNK were increased significantly （P＜0.01），while the protein expression of IκBα was decreased significantly（P＜0.01）. After intervention of couplet medicinals of A. bidentata -E. ulmoides ，the level of inflammatory factors ，the expression or phosphorylation of above proteins were reversed significantly （P＜0.05 or P＜0.01），and couplet medicinals of A. bidentata-E. ulmoides had a synergistic effect. CONCLUSIONS The couplet medicinals of A. bidentata -E. ulmoides have synergistic anti-inflammatory effect on RAW 264.7 cells. Its mechanism may be related to the inhibition of NF-κB/MAPK signaling pathway related protein expression.