When the patient suffers from sepsis, pulmonary capillary endothelium is damaged and vascular permeability increases. A large amount of protein-rich exudate destroys the barrier of pulmonary epithelial cells and accumulates in alveoli, which reduces effective ventilation and results in refractory hypoxemia, this is known as acute lung injury. Acute lung injury caused by sepsis is a common disease in intensive care unit, which has high hospital costs and high mortality. Meanwhile, it is also the focus of research on critical diseases. In this paper, the related literature were reviewed from four aspects, such as the mechanism of vascular endothelial injury, the mechanism of alveolar epithelial injury, the reduction of vascular endothelial injury and the protection of alveolar epithelium and the promotion of repair.

Objectives To study the role and associated potential molecular mechanism of osteopontin/insulin-like growth factor 1 (OPN/IGF1) in the corticospinal tract (CST) regeneration. Methods A total of 28 adult C57BL/6 mice (6-8 weeks old) were randomized into the experimental group (injection of AAV-OPN/IGF1, n=14) and control group (injection of AAV-PLAP, n=14) after training of single pellet retrieval. After received the unilateral pyramidotomy surgery, animals received AAV-OPN/IGF1 or AAV-PLAP at the injury site. Further, we employed the movement behaviour test to evaluate spinal motor recovery at 2-week intervals till 12-week after surgery. The protein kinase Cγ (PKCγ) staining in the dorsal funiculus of the cervical spinal cord indicated surgical efficiency. Lastly, we examined the axon sprouting and expression levels of ribosomal protein S6 kinase (pS6)and insulin-like growth factor receptor (IGFR) in neurons using immunohistochemical staining to study the potential mechanism of OPN/IGF1 to promote axon prouting. Results After evaluating PKCγ staining to indicate surgery effectiveness, a total of ten mice were in the experimental group and eight in the control group. In the mouse unilateral pyramidotomy model, OPN/IGF1 has not much effect on the recovery of motor function compared with the control group. After the overexpression of OPN/IGF1 on cortical neurons, sprouting of the spared CST was increased by the elevated expression of pS6 and IGFR, and the difference was statistically significant (P<0.05). Conclusions OPN/IGF1 promotes the sprouting of the CST by increasing the expression of neuronal IGFR and pS6.

Objective To establish an animal model of high altitude pulmonary edema (HAPE) in the plateau field laboratory, and explore the preventive effect of Betelnut polyphenols on HAPE. Methods Thirty-six Wistar rats were randomly divided into 6 groups (6 each): control group (4 ml normal saline), HAPE model group (4 ml normal saline), rhodiola group(280 mg/kg Rhodiola capsule) and Betelnut polyphenol group with different doses (400, 800 and 1200 mg/kg Betelnut polyphenol).All animals except those in control group were rushed into the high altitude laboratory at an altitude of 4010 m 3 days after preventive administration and assisted with exhaustive exercise on the running platform, the animals in control group kept in the 940th Hospital of PLA Joint Logistics Support Force. One hour after last administration, abdominal aortic blood, bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The arterial oxygen saturation (SatO₂), blood pH, arterial carbon dioxide partial pressure (PaCO₂), arterial oxygen partial pressure (PaO₂), plasma actual bicarbonate (HCO₃^-), standard bicarbonate (SBC) and other blood gas indexes were measured with blood gas analyzer; lung water content (LWC), protein content of BALF and the activity of superoxide dismutase (SOD), contents of malondialdehyde (MDA) and glutathione (GSH) in lung tissues were measured;pathological structure of lung tissue was observed by HE staining. Results Compared with control group, the levels of SatO₂, pH value, PaO₂, PaCO₂, PO₂/FIO₂, SBC, TCO₂, and HCO₃^- decreased significantly in HAPE model group (P<0.05 or P<0.01), the levels of LWC and BALF protein increased significantly (P<0.01), SOD activity and GSH content of lung tissues decreased, and MDA content of lung tissues increased (P<0.05), the normal structure of lung tissue was destroyed. Compared with HAPE model group, the levels of SatO₂ and pH value of low, medium and high dose Betelnut polyphenols groups increased significantly (P<0.05 or P<0.01), the levels of LWC and BALF protein in those groups decreased (P<0.01), the SOD activity and GSH content in lung tissues of medium and high dose Betelnut polyphenols groups increased significantly (P<0.01), the MDA content in high dose Betelnut polyphenols group decreased significantly (P<0.05). HE staining showed that, the alveolar wall was thickened significantly,the alveolar cavity was narrowed, red blood cells and pink protein existed and accompanied with inflammatory cell infiltration in HAPE model group; after preventive administration, the alveolar structure of rats in the low, medium and high doses of Betelnut polyphenol groups tended to be complete, the alveolar wall became thinner, the exudation in the alveolar cavity decreased or even disappeared, and the inflammatory cells decreased. Conclusions The HAPE rat model can be successfully established by rushing to high altitude and exhausting exercise with running platform, and the preventive administration of Betelnut polyphenol 800 and 1200 mg/kg can effectively prevent the occurrence of HAPE.

Objective To investigate the curative effect and possible mechanism of berberine in treatment of rats with acute radiation enteritis. Methods Thirty-two male SD rats were randomly divided into blank control group, model group, berberine group and dexamethasone group (8 rats each). Rats in blank control group received pseudo-irradiation, and in remaining groups were irradiated with 12 Gy ⁶⁰Co γ ray to establish acute radiation enteritis model. Rats in berberine group were given 50 mg/(kg.d)berberine by gavage, in dexamethasone group were given 0.12 mg/(kg.d) dexamethasone by gavage, and rats in model group and blank control group received gavage with the same amount of normal saline. All the gavage continued for 7 days, then the serum and intestinal tissue of rats were taken and stored for later use. The weight and defecation of rats were observed, HE staining was performed to observe the histopathological changes of rat intestinal tissues and count the number of crypts, Masson staining was used to observe the deposition of collagen fibers in rat intestinal tissues, and ELISA was performed to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β and lipopolysaccharide (LPS). The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in intestinal tissues were detected with test kit. The IEC-6 cells were divided into blank control group,model group, berberine group and dexamethasone group. IEC-6 cells in blank control group received pseudo-irradiation, in the rest groups were used to establish the IEC-6 cell radiation damage model, and each group was added with the corresponding medicine serum and co-cultured. qPCR was performed to detect the expression levels of IEC-6 cytochrome C, Bax, Bcl-2, and caspase-3 mRNA in each group. Results The body weight and defecation of rats in berberine group were better than those in dexamethasone group (P<0.05); no obvious intestinal structure damage was found and the proliferation of collagen fibers reduced significantly in rats of berberine group. The number of intestinal crypts was significantly more in berberine group than in model group (173.67±2.33 vs. 115.67±1.45, P<0.05), while no significant difference on the number of intestinal crypts existed between berberine group and dexamethasone group (P>0.05). The levels of IL-6, TNF-α, IL-1β, and LPS in the intestinal tissues of rats were significantly lower in berberine group than in model group, and the IL-6 level was lower in berberine group than in dexamethasone group (P<0.05). The MDA content was significantly lower and the SOD activity was increased in both berberine group and dexamethasone group than in model group (P<0.05), and the MDA content was lower in berberine group than in dexamethasone group (P<0.05). Compared with model group, the expression levels of Bax, caspase-3 and cytochrome C mRNA in IEC-6 cells decreased significantly in berberine group and dexamethasone group, and of Bcl-2 mRNA increased significantly (P<0.05). But no significant difference existed in the expression levels of Bcl-2, Bax, caspase-3 and cytochrome C mRNA in IEC-6 cells between berberine group and dexamethasone group (P>0.05). Conclusion Berberine can effectively improve the inflammatory response of acute radiation enteritis and protect intestinal crypts, the mechanism may be related to reducing the oxidative stress of intestinal tissues and regulating the expression of apoptosis protein in IEC-6 cells.

Objective To explore the expression and clinical significance of GALNT2 protein in lung adenocarcinoma(LAC) based on data mining. Methods GALNT2 gene expression in LAC was analyzed using Oncomine database. UALCAN analysis platform was used to analyze the relationship between GALNT2 gene expression in The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets and clinical features, and KM-plotter website was used to analyze the relationship between GALNT2 gene expression in LAC and prognosis. The mutations of GALNT2 gene in LAC from TCGA dataset were explored using cBioportal online analysis tools. The related protein networks were constructed for function enrichment analysis by using String database. Results The data in the Oncomine database showed that the mRNA expression and DNA copy number variation (CNV) of GALNT2 in LAC tissues were significantly higher than those in normal tissues (P<0.01). The transcription and protein level of GALNT2 in tumor tissues in LAC patients were significantly higher than that in marching tissues,but its expression level had no correlation with the clinical pathological characteristics of patients. A total of 52 samples of 503 LAC samples had GALNT2 gene mutation, and the mutation rate was about 10%. Survival curve analysis showed that the overall survival periods of GALNT2 high expression group and GALNT2 mutation group were shorter than those of GALNT2 low expression group and no mutation group (P<0.01). Multivariate Cox regression analysis showed that the high expression of GALNT2 was an independent risk factor of prognosis in LAC (HR=1.48, P=0.01). String database analysis revealed that GALNT1, RAB6A, RAB6B,DYNC1H1, DYNC1LI1, DCTNs, CAPZAs and mucins had obvious interactions with GALNT2, and these proteins were mainly involved in minus-end-directed organelle transport along microtubule, protein O-linked glycosylation via serine/threonine, O-glycan processing and IL-17 signaling pathway. Conclusions GALNT2 can be highly expressed in LAC tissues, has a high frequency of gene mutation, and may be related to poor prognosis of patients using data mining methods, thus providing a theoretical basis for further research on the role of GALNT2 in the occurrence and progression of LAC.

Objective To analyze the disease burden of benign prostatic hyperplasia (BPH) in China from 1990 to 2019. Methods Data were obtained from the Global Burden of Disease Study 2019. The prevalence, incidence, years lived with disability(YLD) and their corresponding age-standardized rate were used to compare the burden of BPH between China and the world from 1990 to 2019. In addition, a comparative analysis of YLD among 6 urinary diseases was also performed. Results In 2019,the prevalent cases and incidence cases of BPH in China was approximately 20.34 million and 2.84 million, respectively, and the standardized prevalence rate and standardized incidence rate were 2220.85/100 000 and 280.64/100 000, respectively. In addition,the number of YLD due to BPH was approximately 0.41 million and the standardized YLD rate was 44.04/100 000. Compared with 1990, the prevalent cases, incident cases and YLD increased by 125.06%, 122.38% and 123.93% respectively, while the standardized prevalent rate, standardized incident rate and standardized YLD rate decreased by 14.69%, 10.09% and 14.83%, respectively. In 1990 and 2019, the prevalence rate and YLD rate of BPH in China were the highest in the age group ≥80 years old and increased with age.The incidence rate increased in the age group under 79 years old, but decreased in the age group ≥80 years old. In 2019, the YLD of BPH accounted for 61.15% of the 6 urinary diseases, which was 4.11 times that of prostate cancer. Conclusion The disease burden of BPH in China remains at a high level in 2019. Health concerns and guidance on prevention and control should be strengthened for middle-aged and elderly men.

Objective To investigate the clinical characters and influence factors of immune-related thyroiditis(irT) brought by the immune checkpoint inhibitors (ICI) in treatment of malignant tumor. Methods The clinical data were retrospectively analyzed of 286 certificated patients treated with ICI in the Department of Oncology, the First Medical Center of Chinese PLA General Hospital during 2019-2020. The patients were divided into irT group (n=83) and non-irT group (n=203)according to the occurrence of thyroid dysfunction, and the differences between the two groups were compared of age, gender,tumor origin, previous treatment history and ICI types. Then the patients were divided into different subgroups according to the clinical manifestations or severity of irT, then the time of thyroid injury occurrence, auto-antibody level and recovery degree of thyroid dysfunction were compared and analyzed among different subgroups. Results Of the 286 certificated patients, 83 patients(29.0%) developed irT, those with lower age and history of radiotherapy had greater incidence rate. The clinical manifestation of irT included hyperthyroidism (n=28, 33.7%), hypothyroidism (n=48, 57.8%) and transient thyroiditis with normal thyroid function(n=7, 8.4%). All the 83 irT patients, 76 patients (91.6%) only developed mild irT, while 7 patients (8.4%) were severe. In the 28 patients initially diagnosed as immune-related hyperthyroidism, 7 patients (25%) progressed to secondary hypothyroidism in the later course with faster evolution rate than the patients with primary thyroiditis. There was no statistical difference in irT incidence among the patients treated with 4 frequently used PD-1 inhibitors (Pembrolizumab, Nivolumab, Sintilimab and Toripalimab).Among the 83 irT patients, the serum thyroid auto-antibodies levels were often elevated in irT patients. The thyroglobulin antibody(TGAb) was elevated in 23 patients (29.5%) and the thyroid peroxidase antibody (TPOAb) were elevated in 14 patients (12.8%).The TGAb and TPOAb levels were significantly higher in severe irT patients than that in mild patients. The symptoms in most irT patients were reversible and the treatment was tolerable. Only 3 patients (3.6%) stopped ICI treatment due to intolerable symptoms. Conclusions The incidence of irT during immunotherapy was relatively high and its clinical manifestations progressed rapidly.Continuously monitoring the thyroid function should be done during ICI treatment. The clinicians should treat the irT patients promptly according to their clinical stages and symptoms.

Objective To observe the effect of rifaximin with Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules on diarrhea-predominant irritable bowel syndrome (IBS-D) in patients with small intestinal bacterial overgrowth (SIBO). Methods From July 2018 to December 2019, 114 IBS-D patients with SIBO were randomly divided into probiotics group (n=64) and combined group (n=50). The probiotics group was treated by Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules, while the combined group was treated by rifaximin with Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules. The treatment lasted for 14 days. After treatment, the symptom and serum cytokines were compared between the two groups. Results Before treatment, there were no significant differences in the symptom and accompanied symptoms between the two groups (P>0.05). After treatment, the frequency of abdominal pain, the degree of abdominal distension, the obstruction of intestinal symptoms in life, the symptom severity scale (SSS) total score, the number of patients with emergency defecation and mucus stool of the two groups were relieved or reduced as compared with pre-treatment,and the degree of abdominal pain, the number of patients with abdominal distension in the combined group were relieved or reduced than those before treatment (P<0.05). At the same time, the combined group was superior to the probiotics group in the degree of abdominal pain, the frequency of abdominal pain, the degree of abdominal distension, the SSS total score, the number of mild cases,and the number of patients with abdominal distension (P<0.05). The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α),D-lactic acid (D-LA) and lipopolysaccharide (LPS) in the two groups were lower than those before treatment, and the levels of IL-6,TNF-α and LPS in combined group were lower than those in probiotics group (P<0.05). The negative conversion rate of SIBO in combined group was higher than that in probiotics group (76.0% vs. 46.9%), and the difference was statistically significant(P<0.05). Conclusions Both Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules and rifaximin can reverse SIBO and relieve IBS-D symptoms. The effect of the combination of the two drugs is better than that of the single use of the capsules. IBS-D with SIBO is a reasonable indication for rifaximin.

Objective To compare the clinical biochemical features, metabolic abnormalities, difference of hormone level and related factors between male and female patients with subclinical Cushing's syndrome (SCS). Methods The clinical data of 118 SCS patients (38 males and 80 females), admitted in the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital from January 2010 to January 2020, were retrospectively analyzed. The clinical characteristics, biochemical indices, metabolic disturbance, circadian rhythm of plasma adrenocorticotropic hormone (ACTH) and cortisol levels (ACTH-F),ACTH and cortisol levels at 08:00 am. after 1 mg dexamethasone suppression test (1 mg DST) and classical low-dose dexamethasone suppression test (low-dose DST) were compared between male and female SCS patients. Logistic regression analysis of F_00:00, 1 mg DST-F_08:00 and low-dose DST-F_08:00 levels was performed for SCS patients of different genders. Results The BMI, triglyceride level and the proportion of abnormal glucose metabolism were obviously higher in male SCS patients than those in female patients[(28.08±8.30) kg/m² vs. (25.57±3.76) kg/m², P=0.026; (1.68±1.04) mmol/L vs. (1.35±0.69) mmol/L, P=0.045 and 60.5% vs. 37.5%, P=0.019], while no statistical difference existed between male and female patients in age, course of SCS, blood pressure levels, morbidity of hypertension, bone density and bone metabolic markers etc. The 1mg DST-F_08:00 and low-dose DST-F_08:00 were significantly higher in female than those in male SCS patients, and the significant difference still existed after adjusting for age, onset age, BMI and course of disease. Meanwhile, no significant effect was detected on F_00:00, 1mg DST-F_08:00 and low-dose DST-F_08:00 between premenopausal and postmenopausal female patients. Conclusion The BMI, triglyceride level and the proportion of abnormal glucose metabolism were lower in female than in male SCS patients, but the F_00:00, 1mg DST-F_08:00 and low-dose DST-F_08:00 were higher in female than in male SCS patients, and such differences still existed after adjusting for age, onset age, BMI and course of disease.

Objective To explore the factors affecting the prognosis of pancreatic cancer after radical resection for establishing a prognostic prediction model, based on the preoperative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI). Methods The clinical data of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) from January 2013 to December 2019 were retrospectively analyzed. The Kaplan-Meier method was used for survival analysis, the NLR and PNI cut-off values were determined by X-tile software, and the Cox risk ratio model was used to analyze the factors affecting the prognosis of pancreatic cancer. R 4.0.3 software was used to draw a nomogram clinical prediction model of 1, 2, and 3-year survival rates, to evaluate the effectiveness of the prediction model and to establish a web calculator. Results A total of 148 patients were enrolled in the study. The median survival time was 18.2 months. The 1, 2, and 3-year survival rates were 70.8%, 35.8%, and 12.2%,respectively. The cut-off values of NLR and PNI before operation were 1.85 and 44.13, respectively. Combining the two to form NLRP score: 0, 1, and 2. The higher the score, the worse the prognosis (P<0.05). Cox multivariate analysis suggests age >65 years old, high N stage, high TNM stage, no postoperative chemotherapy, postoperative pancreatic fistula and high NLRP score were independent factors affecting the prognosis of pancreatic cancer (P<0.05). The internal verification consistency index (C-index) of the prediction model was 0.710, the calibration curve fitted well, the decision curve showed that the nomogram had a wider clinical net benefit, and the web calculator worked well. Conclusions The NLRP score combined with NLR and PNI can be considered as a new independent prognostic biomarker after radical resection of PDAC. By incorporating the NLRP score into the nomogram, a more accurate and advanced predictive model will be obtained, and the web calculator will be more convenient for doctors and patients to use.