Abstract: Objective　To explore the epidemiological and clinical characteristics of non-tuberculous mycobacterial(NTM) pulmonary disease in Hainan in recent years, and to provide data support for the prevention and treatment of NTM pulmonary disease. Methods　Medical records of patients diagnosed with NTM pulmonary disease who treated at the Second Affiliated Hospital of Hainan Medical University (Hainan Provincial Tuberculosis Hospital) from January 2018 to December 2022 were collected. The demographics, regional distribution, temporal distribution, distribution of mycobacterial species, clinical symptoms, and radiological imaging changes of these patients were analyzed. Results　A total of 225 confirmed cases of NMT pulmonary disease were collected in this study, with 133(59.1%) female patients outnumbering 92(40.9%) male patients. The disease predominantly affected people over 50 years old, with 192 cases (85.3%), and the major onset age range was 61-<81 years old, with a median age of 63 and an average age of 62. Farmers comprised the majority of the patients, with 112 cases (49.8%). More patients were from the western region (90 cases, 40.0%) than from the central region (76 cases, 33.8%), followed by the eastern region (59 cases, 26.2%). A total of 10 strains were detected from 225 samples, with the most common strains being Mycobacterium intracellulare (92 cases, 40.9%), Mycobacterium chelonae/abscessus(80 cases, 35.6%), and Mycobacterium avium (15 cases, 6.7%), followed by Mycobacterium kansasii (5 cases, 2.2%), Mycobacterium fortuitum (4 cases, 1.8%), and Mycobacterium parascrofulaceum (3 cases, 1.3%). There were 10 cases (4.5%) of mixed infections, including Mycobacterium avium and Mycobacterium intracellulare (8 cases, 3.6%), Mycobacterium intracellulare and Mycobacterium chelonae/abscessus (1 case, 0.4%), and Mycobacterium fortuitum and Mycobacterium chelonae/abscessus (1 case, 0.4%). The primary clinical manifestations of NTM pulmonary disease included cough and sputum (219 cases, 97.3%), hemoptysis (92 cases, 40.9%), fever (61 cases, 27.1%), dyspnea (57 cases, 25.3%), night sweats (52 cases, 23.1%), weight loss (50 cases, 22.2%), and thoracodynia (35 cases, 15.6%). There was no significant difference in symptoms between male and female patients. Pleural thickening (188 cases, 83.6%) and bronchiectasis (151 cases, 67.1%) were the most common imaging changes in NTM pulmonary disease, followed by cavities (93 cases, 41.3%), emphysema (41 cases, 18.2%), and lung damage (28 cases, 12.4%). Male patients were more likely to have lung damage and emphysema, while female patients were more likely to have bronchiectasis. Conclusions　The distribution of NTM species is diverse in Hainan area, with Mycobacterium intracellulare, Mycobacterium chelonae/abscessus, and Mycobacterium avium are dominant species. NTM pulmonary disease and pulmonary tuberculosis have similar clinical features, which requires attention for differentiation in clinical practice.

Objective To investigate the clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumours(IMT)in middle-aged and elderly patients.Methods The clinical,pathologi-cal morphology,immunophenotype and follow-up results of 5 cases of intestinal IMT in middle-aged and elderly patients were retrospectively analyzed.Results 4 cases of IMT occurred in the right half colon and 1 in the ileum.Most patients(3/5)had a history of intestinal injury,starting the digestive tract symptoms and increased leukocytes.The tumor tissue was composed of fusiform myofibroblasts and fibroblasts arranged in storiform pattern,with an infiltrative growth pattern,accompanied by a large number of lymphocytes and plasma cells infiltration,collagen formation and myxedema.One case was atypically large and deformed.Immunophenotype:vimentin(5cases),SMA(5 cases),desmin(3 cases),ALK(3 cases),CK(2 cases)were positive.Caldesmon,CD34,β-catenin,MC,CD117,DOG1,S-100,BCL-2,CD99,CD68 were negative,and Ki-67 proliferation index was 1.28%to 10.01%.All the 5 cases underwent complete tumor resection and were followed up for 48.5 to 133 months.Among them,1 patient aged 83 was considered to have tumor recurrence 27 months after surgery.The other patient survived 122 months without tumor and died of other causes.All the others survived without tumor and were in good condition.Conclusion(1)Intestinal IMT in the middle-aged and elderly people in this group was more common in the right half colon,and most of them had a history of intestinal injury,first gastrointestinal symptoms and elevated white blood cells;(2)Vimentin and SMA were positive at the same time,and ALK was more positive;(3)4/5 patients had good surgical resection,and 1/5 patients could relapse 2～3 years after surgery;old age,ALK-positive,Ki67 up to 10%,atypia may be an important risk factor for intestinal IMT recurrence in the elderly,of which ALK-positive patients may have a recurrence risk of 1/3.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective:To explore the characteristics of gut microbiota in the preoperative, short-term postoperative and long-term postoperative period at (15.61±4.51) months in children with ventricular septal defect (VSD) of congenital heart disease (CHD) treated with cardiopulmonary bypass (CPB).Methods:A prospective study was conducted.In Guangzhou Women and Children′s Medical Center, 13 patients with VSD who were scheduled for CPB and additional 10 age- and gender-matched healthy infants as pre-CPB control group from January 2021 to January 2022 were enrolled.Fecal samples were collected at pre- and early post-CPB.Meanwhile, 18 gender- and CHD diagnosis and operation-matched patients at (15.61±4.51) months after CPB and 8 healthy age- and gender-matched children as long-term control group after CPB were also enrolled, and fecal samples were collected.16S rRNA sequencing of fecal samples from all subjects were performed and comparing the differences in gut microbiota between two groups via comparing alpha and beta diversity, parameter test or nonparametric test, and LEfSe analysis.Results:Compared with those of pre-CPB control group, there was a significant difference in the composition of gut microbiota in the preoperative period of VSD children, with significantly increased abundances of Enterobacteriaceae and Shigella, and decreased abundance of Bifidobacterium (all P<0.05). The diversity of gut microbiota was comparable in VSD children before CPB and in the short period time after CPB (all P>0.05), except for the abundances of Clostridium and Streptococcus (all P<0.05), and there was no significant difference in the relative abundances of other highly abundant gut bacteria between the two periods (all P>0.05). Compared with that in VSD children in the short period time after CPB, the abundances of short-chain fatty acids-producing microbes were significantly higher at (15.61±4.51) months postoperatively (all P<0.05), and the gut bacteria profile was similar to that of the long-term control group after CPB (all P>0.05). Conclusions:Gut microbiota imbalance exists in VSD children before CPB.The gut microbiota profile is not influenced by CPB, which returns normal at (15.61±4.51) months postoperatively.

Objective:To study the clinicopathological characteristics, treatment and prognosis in lupus nephritis (LN) patients with renal thrombotic microangiopathy (TMA), so as to provide more theoretical basis for clinicians to recognize and treat this disease.Methods:The clinical data of LN patients who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from January 1, 2012 to May 31, 2019 were retrospectively collected and analyzed. According to renal clinicopathological examination, the patients were divided into renal TMA group and non-renal TMA group. The clinical data, laboratory examination, renal pathological examination, therapeutic measures and prognostic between the two groups were compared. Follow-up end points were defined as composite ends, including all-cause death, entry into end-stage renal disease, and estimated glomerular filtration rate decrease>50% of baseline. Kaplan-Meier survival curve and log-rank test were used to compare the difference of survival rate between the two groups, and multivariate Cox regression equation was used to analyze the risk factors of endpoint events in LN patients.Results:A total of 1 133 patients with LN were enrolled in this study. Patients with renal TMA were more likely to have hypertension ( χ2=16.310, P<0.001), higher baseline serum creatinine ( Z=-6.918, P<0.001) and 24-hour urine protein ( Z=-2.232, P=0.026), and higher renal pathology activity index (AI) score ( Z=1.957, P=0.001)and chronic index (CI) score ( Z=1.836, P=0.002). The proportions of hormone shock ( P<0.001) and plasma exchange ( P<0.001) in the renal TMA group were higher than those in non-renal TMA group. After treatment of (12±2) months, patients in the renal TMA group had a lower complete response rate ( χ2=10.455, P=0.001) and a higher non-response rate ( χ2=6.047, P=0.014) than those in non-renal TMA group, and were associated with worse prognosis (Log-rank test χ2=26.490, P<0.001). Renal TMA was an independent risk factor for poor prognosis ( HR=2.347, 95% CI 1.210-4.553, P=0.012). Conclusions:Compared with LN patients without renal TMA, LN patients with renal TMA are more likely to have hypertension, with higher serum creatinine, 24-hour urinary protein, AI and CI, suggesting poorer treatment response and renal prognosis. Moreover, renal TMA is an independent risk factor for poor prognosis in patients with LN.

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.

Objective: To evaluate the effects of office blood pressure(OBP)combined with ambulatory blood pressure monitoring(ABPM)on the diagnosis of hypertension. Methods: The residents aged 35-79 years without hypertension history,whose casual OBP were 120~159 mm Hg/80~99 mm Hg,were enrolled from 4 communities of Hangzhou and Zhuji from 2015 to 2018. They were performed OBP measurements on other two days in 4 weeks and ABPM in a week. There were 2 criteria of OBP as elevated OBP on the first day or in 3 different days,and 4 criteria of ABPM as elevated mean BP in 24 hours, daytime, nighttime and either of the above time. Receiver operating characteristic(ROC)curve was employed to evaluate the effects of different OBP criteria combined with ABPM criteria on the diagnosis of masked hypertension(MH)and white-coat hypertension(WCH). Results: Taking 3-day-OBP as a golden standard,the 1-day-OBP with 4 ABPM criteria had the areas under the ROC curve(AUC)of 0.79-0.81,sensitivity of 57.58%-62.77% and specificity of 100.00% in MH;had the AUC of 0.95-0.98,sensitivity of 100.00% and specificity of 88.96%-96.80% in WCH. The Kappa values were all less than 0.6,known as low consistency. Taking either time of ABPM as a golden standard,24 hours,daytime and nighttime ABPM criteria with OBP had the AUC of 0.90-0.92,sensitivity of 79.17%-83.90% and specificity of 100.00% in MH(all Kappa>0.6),when with 1-day-OBP,the Kappa values were all more than 0.8,known as high consistency;had the AUC of 0.95-1.00,sensitivity of 100.00% and specificity of 89.54%-99.37% in WCH,the Kappa values of daytime ABPM were all more than 0.6,known as high consistency. Conclusions If limited by options, 1-day-OBP could be used instead of 3-day-OBP for detection of WCH or exclusion of MH yet with less accuracy; 24 hours or daytime ABPM instead of either time of ABPM was reliable.

objective:To investigate the tolerability of early enteral nutrition (EN), and to further explore the association of early EN with clinical outcome in critically ill patients with hemodynamic instability.Methods:The adult patients from Zhejiang Provincial People’s Hospital with an expected admission to ICU for at least 24 h were consecutively recruited from May 2014 to May 2016, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed on the first week of ICU admission. Enteral nutrition (EN) started after 6 h of hemodynamic stability (MAP ≥ 65 mmHg) when the patients took vasoactive medication. The patients were divided into three groups based on the timing of EN initiation: early EN group (EN initiation within 48 h of ICU admission), late EN group (EN initiation at more than 48 h of ICU admission), and no initiation of enteral feeding within 7 days of ICU admission.Results:Of 201 patients enrolled, the mean age was 65.3 ± 16.4 years, APACHE II score was 22.4 ± 6.85, and 191 patients (95.0%) took mechanical ventilation. There were no differences in high gastric residual volume, diarrhea, and gastrointestinal (GI) bleeding between the early EN group and late EN group ( P>0.05). Whereas, patients in the no initiation of EN within 7 days of ICU admission had a lower prevalence of gastric residual volume (16.7% vs. 33.3%, P=0.05), but higher prevalence of GI bleeding (47.2% vs. 26.1%, P=0.02). Compared with those in the late EN group and in no initiation of EN within 7 days of ICU admission, patients in the early EN group had lower 28- (30.4% vs. 47.9% vs. 55.6%, P=0.01) and 60-day mortality rates (38.0% vs. 53.4% vs. 63.9%, P=0.017). Multivariate Cox regression analysis showed that the timing of EN initiation on the admission to ICU (early EN vs. late EN, χ 2≥5.83, P<0.05; early EN vs. no initiation of EN, χ 2≥7.90, P<0.01), serum creatinine ( χ 2=5.06, P<0.05), plasma albumin ( χ 2≥6.41, P<0.01), AGI grade ( χ 2≥8.15, P<0.01), and APACHE II score ( χ 2≥9.62, P<0.01) were independent predictors for 28- and 60-day mortality. Conclusions:Early EN on admission to ICU could be tolerated, and is significantly associated with lower risk of 28- and 60-day mortality in critically ill patients with vasoactive medication to maintain hemodynamic stability.

Objective: To identify predictors of pulmonary fibrosis development by combining follow-up thin-section CT findings and clinical features in patients discharged after treatment for COVID-19. Materials and Methods: This retrospective study involved 32 confirmed COVID-19 patients who were divided into two groups according to the evidence of fibrosis on their latest follow-up CT imaging. Clinical data and CT imaging features of all the patients in different stages were collected and analyzed for comparison. Results: The latest follow-up CT imaging showed fibrosis in 14 patients (male, 12; female, 2) and no fibrosis in 18 patients (male, 10; female, 8). Compared with the non-fibrosis group, the fibrosis group was older (median age: 54.0 years vs. 37.0 years, p = 0.008), and the median levels of C-reactive protein (53.4 mg/L vs. 10.0 mg/L, p = 0.002) and interleukin-6 (79.7 pg/L vs. 11.2 pg/L, p = 0.04) were also higher. The fibrosis group had a longer-term of hospitalization (19.5 days vs. 10.0 days, p = 0.001), pulsed steroid therapy (11.0 days vs. 5.0 days, p < 0.001), and antiviral therapy (12.0 days vs. 6.5 days, p = 0.012). More patients on the worst-state CT scan had an irregular interface (59.4% vs. 34.4%, p = 0.045) and a parenchymal band (71.9% vs. 28.1%, p < 0.001). On initial CT imaging, the irregular interface (57.1%) and parenchymal band (50.0%) were more common in the fibrosis group. On the worst-state CT imaging, interstitial thickening (78.6%), air bronchogram (57.1%), irregular interface (85.7%), coarse reticular pattern (28.6%), parenchymal band (92.9%), and pleural effusion (42.9%) were more common in the fibrosis group. Conclusion Fibrosis was more likely to develop in patients with severe clinical conditions, especially in patients with highinflammatory indicators. Interstitial thickening, irregular interface, coarse reticular pattern, and parenchymal band manifested in the process of the disease may be predictors of pulmonary fibrosis. Irregular interface and parenchymal band could predict the formation of pulmonary fibrosis early.

Objective:To investigate the effects of iron deficiency in early life on neurobehavioral manifestations in CDH2 genetic mutation rats, in order to explore interaction between iron deficiency and CDH2 gene mutation in autism-like behavior.Methods:The 16 female SD rats with established CDH2 genetic mutations were randomly divided into 8 rats as iron deficiency group and 8 rats as normal diet control group.After mating, rats were fed low-iron diets during pregnancy and lactation or standard diets as control.The offsprings were randomly divided into 27 rats as iron deficiency group and 27 rats as control group.The voice communication ability of offspring was studied through ultrasonic vocalizations.The data and videos of open-field test, three-chamber social interaction test were recorded by animal behavioral video analysis system(Smart3.0). The characteristics of behavior changes were analyzed by statistical methods.Results:Total number of calls in rats aged 10 day in iron deficiency group[(755.67±161.86)times]were significantly lower than that in the control group[(1461.89±166.57)times]( P<0.05). Total calling duration[(41.77±16.17)s]were significantly lower than that in the control group[(86.22±10.07)s]( P<0.05). There is a certain synergistic effect of CDH2 genetic mutation and iron deficiency on the reduction of total calls in rats aged 6 and 8 day( P<0.05). The total distance, distance in zone-periphery, mean speed in zone-total and mean speed in zone-periphery of rats in iron deficiency group were all higher than that in the control group( P<0.05); the numbers of standing and rearing were reduced( P<0.05). In the second stage of the three-chamber test, the rats in the iron deficiency group had shorter communication time with the new stranger 2 and longer interaction time with the old stranger 1 compared with the control, showing a weakening trend of social ability, but the difference was not statistically significant( P>0.05). Conclusion:Autism-like behavioral changes occurred in rats with iron deficiency in early life and CDH2 genetic mutation, and there is a certain degree of synergy.Iron deficiency and CDH2 mutation may increase the risk of autism spectrum disorder.