Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

BACKGROUND:The imbalance between proliferation and apoptosis of chondrocytes plays an important role in the occurrence and development of osteoarthritis. Previous studies have found that hsa-miR-3202 is involved in regulating the proliferation and apoptosis of various cells. However,no studies have explored the correlation between hsa-miR-3202 and osteoarthritis.OBJECTIVE:To investigate the expression of hsa-miR-3202 in osteoarthritic chondrocytes and its effect on the proliferation and apoptosis of chondrocytes. METHODS:(1) MicroRNAs differentially expressed in osteoarthritic chondrocytes were screened by biogenic analysis. Based on the current research situation at home and abroad,hsa-miR-3202 was selected for follow-up studies,and its target genes were predicted by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. (2) Human normal chondrocyte cell lines C28/I2 in logarithmic growth phase were selected and randomly divided into four groups for culture:in normal group,cells were cultured in normal medium for 24 hours,the medium was then changed to normal medium for another 6 hours of culture,and changed to normal medium for subsequent culture;in lipopolysaccharide group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,the medium was then changed to normal medium for another 6 hours,and changed to normal medium for subsequent culture;in lipopolysaccharide+NC group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,and then transfected with has-miR-3202 mimics control for 6 hours,and the medium was change to normal medium for subsequent culture;in lipopolysaccharide+hsa-miR-3202 mimics group,cells were cultured in lipopolysaccharide-containing medium for 24 hours and then transfected with has-miR-3202 mimics for 6 hours,and the medium was changed to normal medium for subsequent culture. After further 48 hours of culture,the expression level of hsa-miR-3202 was detected by fluorescence quantitative PCR and cell apoptosis was detected by flow cytometry. After further culture of 0-72 hours,cell proliferation activity was detected by cell counting kit-8. RESULTS AND CONCLUSION:Bioinformatics analysis results indicated that hsa-miR-3202 was significantly down-regulated in osteoarthritic chondrocytes. GO functional enrichment and KEGG pathway enrichment showed that the function of hsa-miR-3202 target gene was closely related to cell growth and apoptosis. The results of in vitro cell experiments showed that compared with the normal group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly decreased in the lipopolysaccharide group (P<0.05),while the apoptotic rate was significantly increased (P<0.05). Compared with the lipopolysaccharide group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly increased in the lipopolysaccharide+hsa-miR-3202 mimics group (P<0.05),while the apoptotic rate was significantly decreased (P<0.05). To conclude,the expression of hsa-miR-3202 is down-regulated in osteoarthritic chondrocytes to inhibit cell proliferation and promote cell apoptosis,thus affecting the occurrence and development of osteoarthritis.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

BACKGROUND:The imbalance between proliferation and apoptosis of chondrocytes plays an important role in the occurrence and development of osteoarthritis. Previous studies have found that hsa-miR-3202 is involved in regulating the proliferation and apoptosis of various cells. However,no studies have explored the correlation between hsa-miR-3202 and osteoarthritis.OBJECTIVE:To investigate the expression of hsa-miR-3202 in osteoarthritic chondrocytes and its effect on the proliferation and apoptosis of chondrocytes. METHODS:(1) MicroRNAs differentially expressed in osteoarthritic chondrocytes were screened by biogenic analysis. Based on the current research situation at home and abroad,hsa-miR-3202 was selected for follow-up studies,and its target genes were predicted by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. (2) Human normal chondrocyte cell lines C28/I2 in logarithmic growth phase were selected and randomly divided into four groups for culture:in normal group,cells were cultured in normal medium for 24 hours,the medium was then changed to normal medium for another 6 hours of culture,and changed to normal medium for subsequent culture;in lipopolysaccharide group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,the medium was then changed to normal medium for another 6 hours,and changed to normal medium for subsequent culture;in lipopolysaccharide+NC group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,and then transfected with has-miR-3202 mimics control for 6 hours,and the medium was change to normal medium for subsequent culture;in lipopolysaccharide+hsa-miR-3202 mimics group,cells were cultured in lipopolysaccharide-containing medium for 24 hours and then transfected with has-miR-3202 mimics for 6 hours,and the medium was changed to normal medium for subsequent culture. After further 48 hours of culture,the expression level of hsa-miR-3202 was detected by fluorescence quantitative PCR and cell apoptosis was detected by flow cytometry. After further culture of 0-72 hours,cell proliferation activity was detected by cell counting kit-8. RESULTS AND CONCLUSION:Bioinformatics analysis results indicated that hsa-miR-3202 was significantly down-regulated in osteoarthritic chondrocytes. GO functional enrichment and KEGG pathway enrichment showed that the function of hsa-miR-3202 target gene was closely related to cell growth and apoptosis. The results of in vitro cell experiments showed that compared with the normal group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly decreased in the lipopolysaccharide group (P<0.05),while the apoptotic rate was significantly increased (P<0.05). Compared with the lipopolysaccharide group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly increased in the lipopolysaccharide+hsa-miR-3202 mimics group (P<0.05),while the apoptotic rate was significantly decreased (P<0.05). To conclude,the expression of hsa-miR-3202 is down-regulated in osteoarthritic chondrocytes to inhibit cell proliferation and promote cell apoptosis,thus affecting the occurrence and development of osteoarthritis.

Objective To explore the biological basis of different diseases with the same syndrome for pulmonary related comorbidities(pulmonary hypertension,obstructive sleep apnea syndrome,chronic obstructive pulmonary disease,lung cancer)in idiopathic pulmonary fibrosis(IPF)through genomic bioinformatics analysis.Methods GSE110147,GSE113439,GSE135917,GSE106986 and GSE118370 datasets were downloaded as research subjects.The differential genes between each disease group and the control group were screened.Cytoscape 3.10.0 software was used for topology analysis to screen core genes.OmicShare was used to perform GO and KEGG pathway enrichment analyses on core genes.Results A total of 23 core genes related to IPF was obtained.GO enrichment analysis showed that core genes were mainly enriched in biological processes such as cellular process,metabolic process,biological regulation/biological process,developmental process,localization,response to stimulus,immune system process and signaling;in cellular components such as cellular anatomical entity and protein-containing complex;in molecular functions such as binding,catalytic activity,structural molecule activity,molecular adaptor activity,molecular function regulator and transcription regulator activity.KEGG pathway enrichment analysis showed that core genes were mainly enriched in ribosome biogenesis in eukaryotes,AGE-RAGE signaling pathway in diabetic complications,Th17 cell differentiation,JAK-STAT signaling pathway,RNA polymerase,neutrophil extracellular trap formation.Conclusion Using genomic bioinformatics analysis to explore the core genes and signaling pathways of pulmonary related comorbidities in IPF can reveal the mechanism of different diseases with the same syndrome for pulmonary related comorbidities in IPF to a certain extent.

Background Environmental pollutants can affect N⁶-methyladenosine (m⁶A) level in the body, but the change of m⁶A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m⁶A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg⁻¹ cadmium chloride (CdCl₂) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m⁶A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg⁻¹ cadmium chloride group (P<0.05). The expression levels of m⁶A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg⁻¹ cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m⁶A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m⁶A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m⁶A and miR-21 may be associated with Cd-induced renal fibrosis.

Objective:To investigate the risk factors for textbook outcomes (TO) of intra-hepatic cholangiocarcinoma (ICC) after hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 155 ICC patients who underwent hepatectomy in the First Affiliated Hospital of Sun Yat-sen University from September 2014 to August 2019 were collected. There were 90 males and 65 females, aged 60(range, 26?82)years. Observation indicators: (1) treatment situations; (2) TO situations; (3) analysis of risk factors for postoperative TO. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative sur-vival of patients up to October 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent samples t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test, Yates' calibration chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of indicators (the optimal cut-off value). Results:(1) Treatment situations. Of the 155 patients, 46 cases underwent minor hepatectomy and 109 cases underwent major hepatectomy. Twenty-one of the 155 patients underwent combined bile duct reconstruction. Ninety-five of the 155 patients underwent lymph node dissection, including 41 cases with positive lymph node by postoperative histopathological examinations. The operation time and volume of intraoperative blood loss of the 155 patients were 250.0(range, 95.0?720.0)minutes and 300.0(range, 50.0?15 000.0)mL, respectively. The optimal cut-off values of the operation time and volume of intraoperative blood loss for TO calculated by ROC curve were 247.5 minutes and 325.0 mL, respectively. Of the 155 patients, 44 cases received intraoperative blood transfusion and 10 cases received postoperative blood transfusion (5 cases with intraoperative and postoperative blood transfusion). Seventy-four of the 155 patients had postoperative complications, including 39 cases with mild complications and 35 cases with serious complications. The total duration of hospital stay of the 155 patients was 19 (range, 8?77)days. (2) TO situations. Of the 155 patients, 150 cases achieved R 0 resection, 120 cases had no major postoperative complications, 106 cases had no perioperative blood transfusion, 79 cases had no prolonged duration of hospital stay, 152 cases had no death within postoperative 30 days and 150 cases had no readmission within 30 days after discharge. Of the 155 patients, 56 cases achieved postoperative TO, while 99 patients did not achieve TO. (3) Analysis of risk factors for postoperative TO. Results of univariate analysis showed that preoperative biliary drainage, preoperative Child-Pugh grading of liver function, preoperative asymp-tomatic leukocytosis, preoperative total bilirubin, preoperative alkaline phosphatase, preoperative CA19-9, preoperative CA125, operation time, volume of intraoperative blood loss, tumor diameter, pathological T staging and pathological N staging were related factors for preoperative TO of ICC patients undergoing hepatectomy ( χ2=4.31, 4.31, 4.38, 4.80, Z=?4.15, χ2=10.74, 15.44, 16.59, 27.53, 6.53, 6.77, 9.26, P<0.05). Bile duct reconstruction was also a related factor for postoperative TO of ICC patients ( P<0.05). Results of multivariate analysis showed that preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL were independent risk factors for postoperative TO of ICC patients undergoing hepatectomy ( odds ratio=74.77, 11.73, 2.40,4.86, 6.42, 95% confidence intervals as 1.80?113.39, 1.19?115.54, 1.04?5.53, 1.78?13.26, 2.41?17.11, P<0.05). Conclusions:Preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL are independent risk factors for postoperative TO of ICC patients undergoing hepatectomy.

Objective:To explore the association between statins and colorectal cancer and provide evidence for the prevention of colorectal cancer.Methods:Literatures about statins and colorectal cancer published from January 2000 to January 2020 were retrieved from CNKI, Wanfang data, PubMed and Cochrane Library database. The literatures which met the inclusion criteria were collected, and the Newcastle-Ottawa Scale and Jadad score were used to assess the studies. Meta-analysis was performed with statistical software Revman 5.0 and Stata 12.1.Results:A total of 31 studies, involving more than 1.62 million subjects, were included in the analysis. The case-control study ( RR=0.93, 95% CI: 0.88-0.98), the cohort study ( RR=0.75, 95% CI: 0.63-0.88) and the randomized controlled trial ( RR=0.79, 95% CI: 0.65-0.97) showed moderate protective effect of statins. Using statin <5 years ( RR=0.86, 95% CI: 0.76-0.96), average daily dosage ≥34 mg ( RR=0.81, 95% CI: 0.66-0.98) and lipid-soluble statins ( RR=0.86, 95% CI: 0.74-0.99) also had preventive effect on colorectal cancer; while lovastatin ( RR=1.07, 95% CI: 1.00-1.14) increased the risk of colorectal cancer. Conclusion:Statins have protective effect on colorectal cancer.

Objective:To monitor and analyze the divers’ body load during hyperbaric exposure in deep heliox saturation diving at sea, so as to provide reference for safeguarding the safety and health of divers.Methods:The heart rate and rating of perceived exertion (RPE) of the divers were taken to monitor their body loads and the results were analyzed.Results:The heart rates of the four divers were stable. At 6: 30 (63 m) on the third day of decompression, diver 1 had a very low heart rate of 43 beats/min and diver 3 had a heart rate of 53 beats/min. There was no statistically significant difference in the mean heart rates of divers during saturation exposure and each time point of decompression with those before entering the cabin. The overall RPE results of divers ranged from 6 to 16 points, and the overall trend of development was consistent with the pressure change; the highest load was shown in the stage from 100 m stable pressure to the end of excursion diving, while the loads in other stages were relatively small. The mean value of RPE before entering the cabin was slightly higher than that in the pressurized stage, and it reached the peak in the excursion diving stage and then remained stable in the decompression stage. The RPE results of divers in the second diving bell at the end of excursion diving stage were significantly higher than those before entering the cabin ( t=-4.700, P=0.018). Conclusion:It is of important value to guarantee the operation safety by monitoring the divers’ body loads under high pressure. The combination of monitoring heart rate and RPE results can accurately reflect the body load and is conducive to the safety of diving operation.