Objective To summarize and analyze the composition features of large adrenal mass for guiding the clinical treatment. Methods The clinical data of 493 cases of large adrenal mass (≥4 cm), admitted in the Chinese PLA General Hospital from January 2016 to December 2020, were collected and retrospectively analyzed, including gender, age, reason for first visit,operation or not, postoperative pathological diagnosis and imaging data. According to the endocrine function evaluation results,all the cases were divided into functional adrenal masses (n=264) and non-functional masses (n=229), and then, according to the tumor nature, they were divided into benign masses (n=348) and malignant masses (n=145), the spectrum of large adrenal masses were analyzed. Results (1) The mean age was (47.7±14.3) years old. Adrenal incidentalomas is the mainly reasons for first visit (n=289, 58.6%). (2) Of the 493 patients reviewed, the proportion of functional adrenal masses (n=264) was higher than non-functional masses (n=229) [53.6% vs. 46.4%]. Pheochromocytomas occupied the highest proportion among functional masses(65.5%), Myelolipoma occupied the highest proportion among non-functional masses (22.3%). There was no significant difference in age, gender, lesion location and tumor diameter between functional masses group and non-functional masses group. (3) Of the 493 patients, the proportion of benign adrenal masses was higher than malignant masses [70.6% (348/493) vs. 29.4% (145/493)].Compared with benign masses, the tumor diameter in malignant masses group was significantly larger [(73.85±29.84) mm vs.(67.12±26.69) mm, P<0.05]. Pheochromocytoma occupied the first proportion in both benign (32.2%) and malignant masses(42.1%). There was no significant difference in age, gender, and lesion location between the two groups. Conclusions Among the patients with large adrenal mass (≥4 cm), pheochromocytomas occupied the highest proportion and adrenal incidentalomas was the mainly reasons for visiting doctors. Functional adrenal masses were more than non-functional adrenal masses, and benign masses were more than malignant adrenal masses. Malignant masses showed the larger tumor diameter.

Oddi sphincter is an important valve controlling the biliopancreatic duct passage, and its injury can cause enterobiliary reflux, resulting in a series of long-term complications such as reflux cholangitis, cholecystitis, recurrence of calculi, and even cholangiocarcinoma. As one of the most common diseases of digestive system, choledocholithiasis is increasing year by year in recent years. Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred minimally invasive method for the treatment of choledocholithiasis and has been widely used in clinical practice. But different ERCP procedures may damage Oddi sphincter. This article reviews the effects of ERCPs (endoscopic sphincterotomy, endoscopic papillary balloon dilation, endoscopic sphincterotomy plus balloon dilation, endoscopic endoclip papilloplasty) on Oddi sphincter and their respective advantages and disadvantages and application prospect.

Objective To investigate the role and mechanism of myotubularin-related protein 7 (Mtmr7) in proliferation and migration of mouse vascular smooth muscle cells (VSMCs). Methods The mouse aortic smooth muscle cell line (MOVAS)was cultured. 30 ng/ml of platelet-derived growth factor-BB (PDGF-BB) was used to induce proliferation and migration of VSMCs in vitro. The changes of mRNA and protein expression levels after PDGF-BB intervention in Mtmr7 was assessed by qRT-PCR and Western blotting. To explore the role of Mtmr7 in proliferation and migration of mouse VSMCs, the adenovirus carrying Mtmr7(Ad-Mtmr7) was used to infect VSMCs for overexpression of Mtmr7. MOVAS was divided into control group, Ad-Mtmr7 group,PDGF-BB group and Ad-Mtmr7+PDGF-BB group. The proliferation capacity of VSMCs was analyzed by Ki-67 immunofluorescence staining and cell counting kit-8 (CCK-8) assay. The migration capacity was assessed by scratch assay. The downstream target protein levels of mammalian rapamycin target protein complex 1 (mTORC1) were determined by Western blotting. Insulin (5 mg/L)was used to restore the activity of mTORC1. MOVAS were divided into PDGF-BB group, Ad-Mtmr7+PDGF-BB group and Ad-Mtmr7+PDGF-BB+insulin group. The proliferation, migration and protein levels were measured by methods as the same mentioned above. A model of carotid endothelial injury was established. At 28 days after operation, the protein level of Mtmr7 was determined by Western blotting. The mice were randomly divided into 4 groups (10 each): sham group, sham+Ad-Mtmr7 group,carotid endothelial injury group and carotid injury+Ad-Mtmr7 group. To overexpress Mtmr7, Ad-Mtmr7 (5×10¹⁰ pfu/ml) was injected into the carotid artery immediately after operation and then partly incubated for 30 min. At 7th, 14th and 21st day after operation, the mice were injected the adenovirus via tail vein. Twenty-eight days after modeling, the morphology of carotid artery and the degree of intimal hyperplasia were analyzed by HE staining. Results Compared with control group, the mRNA and protein levels of Mtmr7 were obviously reduced (P<0.001 and P<0.05), the rate of Ki-67 positive cells and the relative number of VSMCs increased (P<0.01 and P<0.001), the rate of wound healing and the protein expression levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 increased (P<0.001 and P<0.05) in PDGF-BB group. Compared with the PDGF-BB group, the rate of Ki-67 positive cells, the relative number of VSMCs (P<0.01 or P<0.001), the rate of wound healing (P<0.001) and the protein levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 (P<0.05) were decreased in Ad-Mtmr7+PDGF-BB group. Compared with the Ad-Mtmr7+PDGF-BB group, the protein levels of p-S6^Ser235/236 and p-4EBP1^Thr37/46 (P<0.01), the rate of Ki-67 positive cells, the relative number of VSMCs (P<0.01 or P<0.001) and the rate of wound healing (P<0.01) were increased in Ad-Mtmr7+PDGF-BB+insulin group. Compared with the sham group, the protein expression level of Mtmr7 decreased significantly (P<0.01) and the ratio of intima/media area increased (P<0.001)in carotid endothelial injury group. Compared with the carotid endothelial injury group, after overexpression of Mtmr7, the ratio of intima/media area decreased significantly (P<0.01) in carotid endothelial injury+Ad-Mtmr7 group. Conclusion Overexpression of Mtmr7 may inhibit the proliferation and migration of VSMCs induced by PDGF-BB in mice, alleviating intimal hyperplasia after vascular injury, which is closely related to the mTORC1 activity reduced by Mtmr7.

Objective To explore the predictive value of fibrinogen (FIB)/albumin (ALB) ratio (FAR), neutrophil (NEU)/lymphocyte (LYM) ratio (NLR) and platelet (PLT)/lymphocyte (LYM) ratio (PLR) to acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods Acute exacerbation COPD (AECOPD) patients hospitalized in the Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical College from September 2019 to July 2021 were selected as AECOPD group (n=96), and patients with stable chronic obstructive pulmonary disease (SCOPD) and without acute exacerbation in the outpatient clinic for nearly three months in the same period were selected as SCOPD group (n=103), and healthy people who had physical examination in the same period were randomly selected as control group (n=80). According to the severity classification, AECOPD patients were divided into grade Ⅰ (n=20), grade Ⅱ (n=33) and grade Ⅲ (n=43). The general data and clinical data of each group were recorded, and the serum C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC),NEU, LYM, PLT, FIB, ALB were detected. In AECOPD patients, carbon dioxide partial pressure (PaCO₂) and arterial oxygen partial pressure (PaO₂) were also detected, the FAR, NLR, PLR and oxygenation index (PaO₂/FiO₂) were calculated. The differences of the above indicators in each group were compared, and their correlation was analyzed. The risk factors of AECOPD were analyzed by multivariate logistic regression, and the receiver operating characteristics (ROC) curves were developed to analyze the significance of each indicator in the prediction of AECOPD. Results The levels of CRP, PCT, WBC, NEU, NLR, PLR and FAR decreased gradually (P<0.05) in control group, SCOPD group and AECOPD group; with the increase of AECOPD severity, the improvement time of patients, the levels of CRP, PCT, WBC, NEU as ell as NLR, PLR, FAR and PaCO₂ increased gradually, and PaO₂/FiO₂ decreased gradually (P<0.05). Pearson or Spearman correlation analysis showed that FAR, NLR and PLR were positively correlated with the severity of AECOPD, improvement time, CRP, PCT, WBC and PaCO₂, but negatively correlated with PaO₂/FiO₂ (P<0.01).Multivariate logistic regression analyses showed that FAR, NLR and PLR were the independent risk factors for AECOPD (P<0.05).ROC curve analysis showed that the AUC value was greater than 0.7 for predicting AECOPD with FAR, NLR and PLR alone or in combined usage, and the sensitivity was 0.990, 0.698, 0.563 and 0.958 respectively, and the specificity was 0.641, 0.883, 0.932 and 0.961. Conclusion FAR, NLR, PLR have certain correlation with the inflammatory level, severity and respiratory function of AECOPD, and joint use of the three indicators for detection may have higher predictive value for its occurrence.

Objective The study explored the effect of the knockout of the NCAPH gene on the proliferation, migration and invasion of pancreatic cancer cells, using NCAPH knockout pancreatic cancer cells generated by CRISPR/Cas9 technology. Methods The expression levels of NCAPH were analyzed in multiple cancer tissues and normal tissues by the Oncomine database.Kaplan-Meier analysis was used to investigate the correlation between the expression of NCAPH and the survival of pancreatic cancer patients. NCAPH-knockout cells using lentivirus were produced using the CRISPR/Cas9 technique. The proliferation-related molecules MEK and ERK were determined by Western blotting. CCK-8, colony formation, wound healing and Transwell assay were adopted to detect cell proliferation, migration and invasion of PANC cells. Western blotting detects the expression of MEK, p-MEK, ERK and p-ERK proteins. Results The results showed that NCAPH was significantly upregulated compared with paracancerous tissues in multiple cancer. Kaplan-Meier survival analysis revealed that patients with high expression of NCAPH were associated with a worse prognosis. The Western blotting showed that CRISPR/Cas9 technology efficiently disrupted the NCAPH gene and inhibited its expression in PANC cells. CCK-8 assay and colony formation assay showed that, compared with the control group, inhibiting the expression of NCAPH can inhibit the cell proliferation at 48, 72, 96 and 120 h (0.488±0.007 vs. 0.411±0.004,0.689±0.004 vs. 0.497±0.010, 1.071±0.034 vs. 0.689±0.020, 1.441±0.038 vs. 0.855±0.025) and the colony formation ability(210.0±2.9 vs. 144.0±16.4), the difference was statistically significant (P<0.05). Cell scratch and Transwell invasion assay showed that, compared with the control group, NCAPH knockout significantly suppressed cell migration (34.9%±1.7% vs. 15.1%±2.1%)and invasion [(351±23.64) cells vs. (194±13.0) cells], the difference was statistically significant (P<0.05). Then, we investigated the molecular mechanisms of this change, compared with the control group, NCAPH knockout significantly inhibited the expression of p-MEK and p-ERK proteins. Conclusion NCAPH knockout might inhibit proliferation, migration and invasion of PANC cells via the MAPK-ERK signaling pathway.

Functional metabolomics is an extension of metabolomics, through detecting changes in endogenous metabolites that are stimulated and disturbed by a particular organism, after obtaining the biomarker, experiments were conducted to verify the functions of the biomarker and the associated enzymes, genes and proteins. The molecular mechanism of pathophysiology can be revealed systematically from the perspective of "metabolite-enzyme-gene-protein", solving the upstream and downstream biological mechanisms of metabolite association. This article reviews and analyzes the current common methods and research strategies of functional metabolomics, the exploration of disease targets and pathogenesis, and the analysis of drug action mechanisms in the field of biomedicine. At the same time, the extended research on the combination of functional metabolomics with network pharmacology and reprogramming metabolomics is summarized, and finally the application prospects of functional metabolomics are analyzed and prospected in the field of biomedicine.

Objective To investigate the effects and mechanism of short chain fatty acids (SCFAs) on lipopolysaccharide(LPS) induced acute respiratory distress syndrome (ARDS) in rats. Methods Twenty male SD rats were randomly divided into control group, model group, low-dose SCFAs group and high-dose SCFAs group (5 each). Rats in control and model groups were given normal saline, in low-dose SCFAs group were given sodium acetate 300 mg/kg, sodium propionate 100 mg/kg and sodium butyrate 100 mg/kg, and in high-dose SCFAs were given sodium acetate 600 mg/kg, sodium propionate 200 mg/kg and sodium butyrate 200 mg/kg by gavage for 7 days in advance. And then the rats in control group were perfused with normal saline, and in the other 3 groups were perfused with LPS (5 mg/kg) into trachea to establish ARDS model. The rats were sacrificed 12 hours after modeling, and the arterial oxygen partial pressure (PaO₂) and lung wet/dry weight ratio (W/D) were measured, and HE staining was performed to observe the pathological changes of lung tissues. The concentrations of tumour necrosis factor (TNF)-α, interleukin(IL)-6 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Western blotting was used to detect c-Jun N-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 mitogen-activated protein kinase(MAPK), p-p38 MAPK, nuclear factor kappa-B (NF-κB) p65 and p-NF-κB p65 protein expression in lung tissues. The expression of tight junction protein ZO-1 and Occludin in colonic tissue were detected by immunohistochemistry. Results Compared with control group, PaO₂ decreased, lung W/D and lung pathological injury score increased, the concentration of TNF-α and IL-6 in serum and BALF significantly increased, and the concentration of IL-10 increased, the relative protein expressions of p-JNK/JNK,p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in lung tissues significantly increased, while the relative expression of ZO-1 and Occludin protein significantly decreased in colonic tissues in model group (P<0.05). Compared with model group, PaO₂ increased, lung W/D and lung pathological injury score decreased, and TNF-α, IL-6 in serum and BALF decreased,the concentration of IL-10 increased further, while the relative expressions of p-JNK/JNK, p-ERK/ERK, p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 protein in lung tissue decreased, and the relative expression of tight junction protein ZO-1 and Occludin in colon tissue increased in low and high dose SCFAs groups (P<0.05). Compared with low-dose SCFAs group, the indexes mentioned above in the high-dose SCFAs group improved more significantly (P<0.05). Conclusion SCFAs could regulate immunity and inflammation, and effectively improved LPS-induced ARDS in rats, the mechanism might be related to enhancement of intestinal barrier and inhibition of MAPK and NF-κB signaling pathway activation, thereby reducing the release of inflammatory factors and increasing the production of anti-inflammatory factors.

Long non-coding RNA (lncRNA) is a kind of non-protein coding RNA with a sequence length of more than 200 bp. It regulates the epigenetic characters of organisms by regulating pre-transcription, transcription, and post-translation modification. Atherosclerosis is a kind of vascular disease that gradually narrowed and blocked due to the atherosclerotic lesions in the large and middle arteries. The mechanisms of initiation and progression of atherosclerosis can be summarized as "Injury-Response" doctrine, which involves lipid deposition, intimal inflammation, cell proliferation and apoptosis. It is reported that lncRNA can regulate the "Injury-Response" process by regulating different gene and molecular expression. Here, we provide a mechanistic review of how lncRNA regulate the "Injury-Response", which will provide reference for the future basic research and clinical diagnosis and treatment.

Objective To investigate the expression levels of serum exosomes integrin α₅, β₅ and β₆ and their clinical significance in patients with different stages of colorectal cancer (CRC). Methods The serum samples were collected from 50 patients with CRC admitted in the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine and Hunan Cancer Hospital from January 2016 to October 2020, and were divided into CRC stage Ⅰ group (n=5), CRC stage Ⅱ group (n=19), CRC stage Ⅲ group (n=14), and CRC stage Ⅳ group (only liver metastasis, n=12) according the TNM stage. The serum samples were collected from 10 healthy people who underwent physical examination in the Health Management Center of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine from August 2018 to May 2020, and set as healthy people group. The exosomes were purified, and then identified by nanoparticle tracking assay (NTA) and Western blotting. The expression levels of integrin α₅,β₅ and β₆ were detected by Western blotting, the survival time of 50 patients with CRC were followed up. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazards model was used for survival analysis. Results The 50 patients with CRC [26 males (52.0%) and 24 females (48.0%)] are mainly middle- and elderly-aged with average age of 58 years. Five cases (10.0%)in TNM stage Ⅰ, 19 cases (38.0%) in stage Ⅱ, 14 cases (28.0%) in stage Ⅲ and 12 cases (24.0%) in stage Ⅳ (only liver metastasis).Up to February 2021, the follow-up time was 5-60 months, and the median follow-up time was 44 months, no cases fell off or lost follow-up. NTA analysis showed that the particle diameter of serum exosomes in all serum samples were concentrated in 50-150 nm.Western blotting results showed that the marker proteins of serum exosomes ALIX and HSP70 were expressed in all serum samples,which confirmed that these extracts were exosomes. Integrin α₅, β₅ and β₆ were expressed in different degrees, the expression levels of integrin α₅ and β₅ increased with the increase of TNM stage, and significantly higher in live metastasis than in non-stage Ⅳ(P<0.05). However, no significant relationship existed between the expression of integrin β₆ and TNM stage (P>0.05). Kaplan-Meier method showed that integrin α₅, β₅ and TNM stage were related with survival of patients with CRC (P<0.05). The results of Cox proportional risk model suggested that integrin α₅ and the degree of pathological differentiation were independent influencing factors of survival in patients with CRC (P<0.05). Conclusion Exosomes integrin α₅, β₅ are related to liver metastasis and TNM stage of CRC. Exosomes integrin α₅ and the degree of pathological differentiation are related to the prognosis of colorectal cancer,and integrin α₅ and β₅ may become potential serum markers.

Monkeypox is a rare viral zoonosis that is mainly endemic in West and Central Africa through animal-to-human transmission. Monkeypox virus has become the orthopoxvirus family which poses greatest threat to public health since smallpox eradication in 1980 s. The clinical manifestations of monkeypox cases are similar, but less severe, to smallpox. There are no specific treatments available for monkeypox infection until now. Until now, 2780 confirmed and suspected cases have been reported in more than 50 countries or regions out of Africa and human-to-human transmission has occurred, which have increasingly drawn attention worldwide. There are no confirmed cases of monkeypox in our country so far, we still need to be highly alert about the outbreak of monkeypox,improve diagnosis and treatment capabilities, and make emergency plans and technical reserves.