Objective To investigate the impact of hyponatremia on the prognosis of neurointensive care patients. Methods A retrospective study of 942 neurointensive care patients admitted to the First Medical Center of PLA General Hospital between August 2010 and May 2020 was performed. We classified these patients into two groups according to serum sodium level within 24 hours of admission: hyponatremia group 233 cases (<135 mmol/L), normonatremia group 709 cases (135-145 mmol/L).The 233 hyponatremia patients were subdivided into two groups: mild hyponatremia group (130-135 mmol/L, n=165) and moderate-severe hyponatremia group (<130 mmol/L, n=68). Primary endpoints were evaluated at 1-month and 6-month respectively with modified Rankin Scale (mRS), mRS scores of 4-6 were defined as poor outcomes. The general clinical data and prognosis were compared between the groups. Logistic regression was used to analyze the influencing factors of patient prognosis. Results Compared with the normonatremia group, the body temperature, blood glucose, urea, and creatinine, diagnosed as cerebrovascular disease, the proportion of poor prognosis at 6 months as well as hospitalization costs in the hyponatremia group were significantly different (P<0.05). There was no significant difference in the prognosis of patients with different degrees of hyponatremia (P>0.05). Multivariate logistic regression showed that hyponatremia, older age, high serum creatinine level, diagnosed as cerebrovascular disease, higher hospitalization costs, and low GCS score were independent risk factor for poor prognosis of NICU patients at 1 month after discharge. And multivariate logistic regression showed that hyponatremia, older age and low GCS score were independent risk factor for poor prognosis of NICU patients at 6 months after discharge. Conclusions Hyponatremia,a common electrolyte disorder in neurointensive care patients, is an independent risk factor influencing prognosis. Even mild hyponatremia may have an impact on outcomes.

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.

Objective To explore a possible solution in clinical practice of fluid therapy for patients with sepsis by reinforcement learning method. Methods A total of 11 913 patients with sepsis were screened by using the Medical Information Mark for Intensive Care (MIMIC) Ⅲ Database, and randomly divided into a training set and a test set according to the ratio of 8:2. Twenty-six features were used in modeling, including 24 state features of patients (bloc, vital signs, laboratory tests, blood gas analysis index and basic information), 1 action feature (liquid inflow and outflow difference) and 1 outcome feature (outcome in ICU). Data rules of SARSA model learning training set were used to get the relationship between return rewards and mortality, so as to evaluate whether the return rewards were reasonably set. Deep Q-learning (DQN), a deep learning model based on Q-learning,models the relationship between the state and behavior of the test set, predicts the patients' fluid balance, and compares the results of reinforcement learning and the actual outcomes of patients, which further proved the different effects of predicted liquid therapy and actual therapy on prognosis. Results According to the behavior category distribution, the differences of liquid inflow and outflow were divided into 5 intervals (–3000 to –239.40 ml, –239.39 to –1.94 ml, –1.93 to 160.00 ml, 160.01 to 363.58 ml, and 363.59 to 3000 ml). The SARSA model calculated the training data set, results showed that the higher the Q (s, a) return, the lower the mortality rate. The DQN model suggested that both too high and too low of the difference between the liquid input and output volume may increase the case mortality, and the mortality of patients is higher in low difference of inflow and outflow than in high difference of inflow and outflow volume. Using Doubly robust estimator to evaluate the DQN model average expected return of the test set showed the stability of the model (Q-learning iteration number >20 000). The use of validation set hinted that the mortality was obvious lower in the subgroups predicted dehydration consistent with the reality than in the other three subgroups, indicating that the model can be used in actual clinical verification. Conclusion A predictive model for possibly guiding the fluid therapy on patients with sepsis is proposed using the reinforcement learning method, which can accurately predict the direction of liquid therapy,patients got a better prognosis by using the model predicted dehydration treatment and dehydration was actually carried out.

Objective To explore the regulatory effect of miR-181a on PTEN-induced kinase 1 (PINK1)/Parkin-related genes (Parkin) pathway, and on mitochondrial autophagy of osteoclasts in osteoporosis (OP) rats. Methods Twenty healthy female SD rats were randomly divided into osteoporosis (OP) model group and control group (10 each). Rats in OP model group were employed to prepare OP model. Osteoclasts were extracted from OP rats, and set them as: OP group (not transfected), si-miR-181a group (transfected with si-miR-181a vector plasmid), si-NC group (transfected with negative control plasmid), ad-miR-181a group (transfected with ad-miR-181a vector plasmid), and ad-NC group (transfected with negative ad-NC control plasmid),and the osteoclasts of rats in control group were cultured normally and set as normal control group. The expression of miR-181a was detected by RT-PCR, and MTT and flow cytometry were performed to detect the survival and apoptosis of osteoclasts, the mitochondria autophagy was observed with transmission electron microscope, the expression of Parkin in mitochondria was detected by immunofluorescence co-localization, Western blotting was performed to detect the expression of PINK1/Parkin and autophagy,as well as apoptosis related proteins. Knockdown of miR-181a in osteoclasts of OP rats to down regulate the expression of Parkin and verify the reversal effect of Parkin on miR-181a. Double Luciferase Report experiment verified the targeted regulation between miR-181a and Parkin. Results Compared with normal control group, miR-181a (1.59±0.15 vs. 1.02±0.11), Parkin⁺TOMM2⁺(2.02±0.20 vs. 0.13±0.10), Parkin (1.83±0.18 vs. 1.13±0.10) in osteoclasts of OP rats, and PINK1 (1.93±0.19 vs. 1.03±0.10)expression and survival rate (157.06%±12.32% vs. 100.09%±0.05%), autophagy marker protein-LC3-Ⅱ/Ⅰ ratio (1.89±0.18 vs. 1.15±0.10) increased (P<0.05). Compared with OP group, after up-regulating the expression of miR-181a in osteoclasts of OP rats, the cell survival rate (222.96%±22.15%) increased, Parkin⁺TOMM2⁺ (1.01±0.11), LC3-Ⅱ/Ⅰ ratio (1.36±0.12) and apoptosis rate (3.28%±0.35%) decreased (P<0.05). While after down-regulating the expression of miR-181a in osteoclasts of OP rats, the cell survival rate (106.96%±10.15%) decreased, Parkin⁺TOMM2⁺ (2.97±0.29), LC3-Ⅱ/Ⅰ ratio (2.47±0.24) and apoptosis rate (19.71%±1.83%) increased (P<0.05). The dual luciferase reporter test showed that Parkin is the target gene of miR-181a. Down-regulating Parkin expression can reverse the effects of miR-181a low expression in promoting mitochondrial autophagy and inhibiting cell survival (P<0.05). Conclusion Up-regulation of miR-181a expression in OP rat's osteoclasts can target down-regulation of Parkin expression, inhibit activation of mitochondrial autophagy, and promote the survival of osteoclasts.

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.

Objective To assess the grading diagnostic value of controlled attenuation parameter (CAP) on hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). Methods Patients with biopsy-proven NAFLD, admitted in the Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2020, were enrolled in present study.The CAP value was detected with transient elastography (TE) within 3 days before liver biopsy. The serological noninvasive models[hepatic steatosis index (HSI) and triglyceride-glucose index (TyG)] were calculated based on their own formula. The relativity between these 3 noninvasive approaches and hepatic steatosis grades were analyzed with Spearman method, the independent influencing factors of CAP value were analyzed using linear multiple regression analysis, the diagnostic efficiency was evaluated with receiver operating characteristics (ROC). Results A total of 405 patients [258 males (63.7%)] with NAFLD were enrolled,and divided into four groups according to hepatic steatosis grades: no steatosis (grade S0, n=17), mild steatosis (grade S1, n=75),moderate steatosis (grade S2, n=163) and severe steatosis (grade S3, n=150). As steatosis grade increasing, CAP value and ALT level increased correspondingly with statistically significant difference (P<0.05). Spearman analysis showed that CAP value, HSI and TyG index were positively correlated with hepatic steatosis grades with correlation coefficient of 0.713, 0.296 and 0.141, respectively (P<0.05).Multiple linear regression analysis showed that hepatic steatosis grade was the independent influential factor for CAP. ROC analysis showed that the diagnostic efficiency of CAP for different hepatic steatosis grades were significantly higher than that of HSI or TyG index,and the areas under ROC curves for CAP diagnosis of S1-S3 grades were 0.876, 0.878 and 0.885 with the corresponding cut-off values of 286, 303 and 314 dB/m, respectively. Conclusion With CAP value the hepatic steatosis grades could be accurately judged in patients with NAFLD, which might help to establish or adjust the optimal treatment strategy, thus having a good clinical application value.

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.

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.

Portal hypertensive enteropathy (PHE) is the appearance of intestinal mucosal capillary stasis and expansion,ultrastructural changes in mucosal epithelial cells, and ectopic varicose veins in patients with portal hypertension (PH), and its scope is limited to intestinal lesions characterized by vascular changes. PHE, including portal hypertensive small bowel disease and portal hypertensive colonopathy (PHC), is one of the important causes of PH complicated by gastrointestinal bleeding. The pathogenesis of PHE is not fully understood, the lack of specificity of histopathological findings, atypical clinical symptoms, and the uniqueness of anatomical location makes its diagnosis difficult. Abdominal CT, multi-slice spiral CT perfusion imaging, ^99mTc-RBC and single photon emission CT (SPECT)/CT can provide certain diagnostic information and help guide follow-up treatment. This article summarizes the research progress of PHE from the aspects of pathogenesis, histopathological findings, clinical manifestations,examination and diagnosis and treatment methods, in order to deepen clinicians' understanding of this disease.