ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

The methodological framework for interventional clinical research of Chinese medicine （CM） under the research mode of syndrome dominating disease provides a set of technical principles and methods to design， evaluate， and implement of this kind. It consists of three main parts including general principles， research points and key design elements， with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects， including basic norms to be followed in relevant studies， perspectives for selecting research topics， as well as the technological details on study population （P）， intervention （I） and comparison（C）， outcome measurement （O）， time frame （T） of treatment and follow-up， sample orientation （prospective versus retrospective）， study design （S） format and type. To provide practical guidance for future studies， this article clearly explains each items of the methodological framework through some supportive cases.

Objective:To understand the situation and epidemic characteristics of injury deaths among children aged 5 to 24 years in Jiangsu Province from 2012 to 2021 and the trend of annual changes.Methods:The main injury mortality data of children and adolescents was collected, and the crude and standardized mortality rates of road traffic accidents, drowning, suicide, and accidental falls among children and adolescents over a decade and the annual average percentage of change (AAPC) were calculated. The main injury mortality characteristics and trends of children and adolescents of different age groups and genders were analyzed.Results:The total number of injury deaths among 5 to 24 adolescents in Jiangsu Province was 16 052, with a standardized mortality rate of 9.58/100 000. There was no significant trend in the overall standardized mortality rate of injuries (AAPC=-3.450%, P=0.055). The standardized mortality rate of road traffic injuries among children and adolescents showed a decreasing trend over the past decade, with statistical significance (AAPC=-9.406%, P<0.001). The standardized suicide mortality rate showed an upward trend over the past decade, with statistical significance (AAPC=9.000%, P=0.001). The overall injury mortality rate showed an upward trend with age. Suicide rates in males and females were on the rise and both have statistical significance (AAPC=9.420% and AAPC=9.607%, both P<0.05). The standardized mortality rates of female traffic accidents, drowning, and male traffic accidents showed a decreasing trend and were statistically significant (AAPC for female traffic accidents=-7.364%, AAPC for female drowning=-5.352%, and AAPC for male traffic accidents=-10.242%, all P<0.05). The standardized mortality rate of urban and rural traffic accidents showed a decreasing trend and was statistically significant(AAPC=-7.899% and AAPC=-9.421%, both P<0.001). The standardized suicide mortality rate showed an upward trend and statistical significance (AAPC=11.009% and AAPC=7.528%, both P<0.05). Conclusions:The overall injury situation of children and adolescents in Jiangsu Province improved in the past decade from 2012 to 2021, but the suicide mortality rate was on the rise. It is necessary to focus on the mental health issues of this age group and to strengthen the prevention and control of suicide among children and adolescents, in Jiangsu.

Objective:To explore the effect of miRNA-511-3p (miR-511-3p) on the proliferation and apoptosis of lung cancer cells, and the possible role of ATP2A2 and endoplasmic reticulum stress therein.Methods:Lung cancer tissues and paracancerous normal tissues (>2 cm from the tumor) were retrospectively collected from 69 lung cancer patients who were admitted to Huizhou Central People's Hospital from January 2020 to March 2022. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the transcript-level relative expression of miR-511-3p in cancer and paracancerous tissues, as well as immortalized lung epithelial cell line BEAS-2B, human lung cell line CCD-19Lu, and human lung carcinoma cell lines A549, H1975 and H1299. The lung cancer cell line A549 with the lowest relative expression level of miR-511-3p was selected for subsequent experiments. The cells were divided into miR control group (transfected with miR-511-3p irrelevant sequence), miR-511-3p overexpression group (transfected with miR-511-3p mimic), and miR-511-3p knockdown group (transfected with miR-511-3p repressor); and the additional A549 cells were taken and divided into ATP2A2 overexpression control group (transfected with its empty plasmid), ATP2A2 overexpression group (transfected with ATP2A2 overexpression plasmid), and ATP2A2 knockdown control group (transfected with irrelevant small interfering RNA plasmid) and ATP2A2 knockdown group (transfected with ATP2A2 small interfering RNA plasmid). The transcript-level relative expression of miR-511-3p and ATP2A2 in A549 cells in each group was detected by qRT-PCR; the relative expressions of ATP2A2 protein and endoplasmic reticulum stress marker proteins in each group were detected by Western blotting; the targeting relationship between miR-511-3p and ATP2A2 mRNA was verified by dual-luciferase reporter gene assay; CCK-8 assay was used to detect the proliferation ability of A549 cells in each group (expressed as absorbance value); flow cytometry was used to detect the percentage of apoptotic cells in A549 cells in each group; inorganic phosphorus colorimetry was used to detect the activity of Ca 2+-ATPase in A549 cells in each group; fluorescent probe assay was used to detect the Ca 2+ concentration in A549 cells in each group. Results:The transcript-level relative expression of miR-511-3p in lung cancer tissues and paracancerous tissues of 69 patients were 0.08±0.03 and 0.17±0.12, respectively, and the difference was statistically significant ( t= 6.04, P<0.05). The percentage of apoptotic cells in A549 cells in the miR-511-3p overexpression group, miR-511-3p knockdown group and miR control group was (58.1±6.1)%, (11.0±1.3)% and (22.0±2.1)%, respectively. The percentage of apoptotic cells in the miR-511-3p overexpression group was higher than that in the miR control group, and the percentage of apoptotic cells in the miR-511-3p knockdown group was lower than that in the control group, and the differences were statistically significant ( t values were 9.70 and 7.64, respectively, both P<0.05). After 24, 48 and 72 h of culture, the proliferation ability of A549 cells in the miR-511-3p overexpression group was lower than that in the miR control group, the proliferation ability of A549 cells in the miR-511-3p knockdown group was higher than that in the miR control group, and the differences were statistically significant (all P < 0.05). The percentage of apoptotic cells in A549 cells of ATP2A2 knockdown group and ATP2A2 knockdown control group were (58.2±1.5)% and (23.8±1.0)%, respectively, and the difference was statistically significant ( t= 33.94, P < 0.05); the percentage of apoptotic cells in A549 cells of ATP2A2 overexpression group and ATP2A2 overexpression control group were (13.8±2.0)% and (23.8±1.0)%, respectively, and the difference was statistically significant ( t= 7.96, P < 0.05). The transcript-level relative expression of ATP2A2 in A549 cells of miR-511-3p overexpression group was lower than that of miR control group, the transcript-level relative expression of ATP2A2 in A549 cells of miR-511-3p knockdown group was higher than that of control group, and the differences were statistically significant ( t values were 5.76 and 6.40, respectively, both P < 0.05); the relative expression of ATP2A2 protein in A549 cells of miR-511-3p overexpression group was lower than that of its control group, and the relative expression of ATP2A2 protein in A549 cells of miR-511-3p knockdown group was higher than that of its control group, and the differences were statistically significant (both P < 0.05). Dual-luciferase reporter gene assay verified the targeting relationship between miR-511-3p and ATP2A2 mRNA. The percentage of apoptotic cells in A549 cells in the control group, miR-511-3p overexpression group, ATP2A2 overexpression group, and miR - 511 - 3p overexpression+ ATP2A2 overexpression group were (21.5±3.0)%, (58.1±5.0)%, (13.3±1.2)%, and (20.5±4.0)%, respectively, and the difference was statistically significant (F= 73.28, P < 0.001); the percentage of apoptotic cells in A549 cells in the control group, miR-511-3p knockdown group, ATP2A2 knockdown group, and miR-511-3p knockdown+ ATP2A2 knockdown group were (23.5±3.0)%, (11.3±1.2)%, (60.1±7.0)%, and (25.6±5.0)%, respectively, and the difference was statistically significant ( F= 78.45, P < 0.001). The Ca 2+-ATPase activity in A549 cells of ATP2A2 overexpression group was higher than that of its control group, the Ca 2+-ATPase activity in A549 cells of ATP2A2 knockdown group was lower than that of its control group, and the differences were statistically significant ( t values were 4.61 and 6.07, respectively, both P < 0.05); the intracellular Ca 2+ concentration in A549 cells of ATP2A2 overexpression group was lower than that of its control group, the intracellular Ca 2+ concentration in A549 cells of ATP2A2 knockdown group was higher than that of its control group, and the differences were statistically significant ( t values were 3.30 and 3.95, respectively, both P < 0.05). The Ca 2+-ATPase activity in the miR-511-3p overexpression group was lower than that in the miR control group, the Ca 2+-ATPase activity in the miR- 511-3p knockdown group was higher than that in the miR control group, and the differences were statistically significant ( t values were 6.54 and 4.16, respectively, both P < 0.05); the intracellular Ca 2+ concentration in A549 cells of miR-511-3p overexpression group was higher than that of miR control group, the intracellular Ca 2+ concentration in A549 cells of miR - 511 - 3p knockdown group was lower than that of miR control group, and the differences were statistically significant ( t values were 3.60 and 6.23, respectively, both P < 0.05). The relative expressions of endoplasmic reticulum stress markers GRP78, PERK, p - eIF2a, ATF4, and CHOP proteins in A549 cells with knockdown of ATP2A2 or overexpression of miR-511-3p were higher than those in the corresponding control groups, and the differences were statistically significant (all P < 0.05); the relative expressions of all proteins in A549 cells with overexpression of ATP2A2 or knockdown of miR-511-3p were lower than those in the corresponding control groups (all P < 0.05). Conclusions:Changes in miR-511-3p level may affect the proliferation and apoptosis of lung cancer cells, and the mechanism may be that it affects the apoptosis of lung cancer cells by targeting ATP2A2 to regulate the endoplasmic reticulum stress.

Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.

Objective:To compare the effect and safety of continuous veno-venous hemofiltration (CVVH)+double plasma molecular absorption (DPMA)+hemoperfusion (HP), CVVH+HP, and CVVH+plasma exchange (PE) in treatment of patient with severe wasp stings injury.Methods:Multicenter, historical cohort study and superiority test were used. From July 2020 to October 2022, patients with wasp sting injury and multiple organ damage admitted to the intensive care units (ICU) of five hospitals were consecutively screened and recruited into the CVVH+DPMA+HP group (intervention group). Propensity score matching was used to establish historical cohorts. Patients with severe wasp sting injury who hospitalized from January 2016 to June 2020 in each ICU were collected and matched 1∶1 with the intervention group, and divided into CVVH+HP group and CVVH+PE group according to their actual hemopurification protocols (historical control groups). The primary outcome was the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on days 3 and 7 after initiation of treatment. Secondary outcomes included complications, length of ICU and hospital stays, and all-cause mortality. Multivariate Cox proportional risk regression was used to analyze the prognosis of patients.Results:After propensity score matching, 56 patients in intervention group and each of the two historical control groups were matched successfully. There were no significant differences in age, gender, comorbidities, biochemical test indices and critical illness scores among the groups. After treatment, APACHE Ⅱ score markedly declined in all groups, and the decrease was faster in the intervention group; treatment with DPMA [hazard ratio ( HR) = 1.04, 95% confidence interval (95% CI) was 1.02-1.08, P = 0.00], the decreased levels of body temperature ( HR = 1.02, 95% CI was 1.00-1.03, P = 0.02), serum creatine kinase (CK; HR = 0.98, 95% CI was 0.96-1.00, P = 0.05) and myoglobin (MYO; HR = 2.88, 95% CI was 1.24-6.69, P = 0.01) were independent risk factors for APACHE Ⅱ score decline to the target value (15 scores). There were no significant differences in the incidence of bleeding complications, filter or perfusion thrombosis, blood pressure reduction, catheter-related infection and anaphylaxis among the groups. Conclusion:CVVH+DPMA+HP regimen can significantly reduce the APACHE Ⅱ score of patients with severe wasp sting injury, and the efficacy is superior to CVVH+HP and CVVH+PE regimens, with safety.

Objective To investigate the characteristics of population and the changes of disease spectrum in patients treated by endoscopic retrograde cholangiopancreatography ( ERCP ) . Methods Data of 20170 patients, who underwent ERCP in the First People' s Hospital of Hangzhou from May 2004 to February 2018, were enrolled in the retrospective analysis. According to the year of diagnosis and treatment,patients were divided into 2004-2008, 2009-2013, and 2014-2018 group; according to the postoperative diagnosis of ERCP, they were divided into biliary tract diseases ( including calculus, benign stenosis, malignant stenosis, and other causes ) and pancreatic diseases ( including acute pancreatitis, chronic pancreatitis, pancreatic malignant tumor, and other causes ) group; and according to the age, they were divided into the younger age (0-18 years old), young and middle age (19-65 years old), old age (66-85 years old), and advanced age (>85 years old) group. Statistical analysis was performed in the different groups. Results Among the 20170 patients, there were 10260 males and 9910 females, with age of 62. 65± 17. 11 years. The proportion of the younger age group and the advanced age group was 1. 04％( 24/2308 ) , 1. 69％ ( 127/7520 ) , 2. 39％ ( 247/10342 ) , and 2. 95％ ( 68/2308 ) , 4. 19％( 315/7520 ) , 6. 15％ ( 636/10342 ) , respectively, in the 2004-2008, 2009-2013 and 2014-2018 subgroups, with a rising trend (P<0. 017). A total 20032 patients had a clear postoperative diagnosis, including 15618 ( 77. 97％) of biliary diseases and 4414 ( 22. 03％) of pancreatic diseases. Biliary stones accounted for the majority of biliary diseases (63. 2％, 9863/15618), and its proportion increased from 59. 9％ ( 1191/1987 ) in 2004-2008 to 64. 5％ ( 5118/7939 ) in 2014-2018 ( P= 0. 000 ) . Acute pancreatitis accounted for the majority of pancreatic diseases (67. 4％, 1973/4414), and its proportion increased from 52. 4％ ( 162/309) in 2004-2008 to 69. 9％ ( 1636/2340) in 2014-2018 ( P=0. 000) . The top 3 diseases in the younger group and the advanced age group were acute pancreatitis ( 32. 58％, 129/396) , biliary stones ( 25. 25％, 100/396 ) , chronic pancreatitis ( 22. 22％, 88/396 ) , and biliary stones (56. 46％, 568/1006), malignant biliary stenosis (12. 52％, 126/1006), benign biliary stricture ( 10. 34％, 104/1006) , respectively. Conclusion The main disease of patients receiving ERCP is biliary stone, and the proportion of acute pancreatitis is increased. The overall age of the patients is old, and the proportion of the elderly and underaged patients is gradually increasing. Biliary diseases and pancreatic diseases are the main diseases in elderly patients and younger patients, respectively.

PURPOSE: The Pipeline embolization device (PED) is approved in the USA for treating giant and large aneurysms arising from the petrous to superior hypophyseal segments of the internal carotid artery in patients older than 21 years of age. This study investigates off-label PED results in a large cohort. MATERIALS AND METHODS: Retrospective, single-center review of all patients who had off-label PED surgery. RESULTS: Sixty-two aneurysms (48 patients) underwent off-label PED treatment from 2012–2017. There were 44 females and four males (age 21 to 75 years; mean/median, 54.3/55.0 years). The most common presenting symptom was headache (47/62, 75.8%). All aneurysms were in the anterior circulation. Aneurysm size ranged from 1.4 to 25.0 mm (mean/median, 7.6/6.9 mm). Fifty-two aneurysms had post-operative imaging with total/near-complete occlusion of 84.6% (44/52). Aneurysm-based operative near-term complication rate was 9.7% while there were no permanent complications. For aneurysms and headache, 86.7% improved/resolved after embo-surgery, and were four times more likely to have a better clinical outcome (resolved or improved symptoms) after surgery (odds ratio [OR], 4.333; P=0.0325). Left-sided aneurysms had a higher occlusion rate (OR, 20; P=0.0073). Hypertension (OR, 4.2; P=0.0332) and smoking (OR, 7; P=0.0155) were more prone towards aneurysm occlusion. Patients without a family history were 14 times more likely to have favorable imaging outcome (P=0.0405). There is no difference of occlusion rates between untreated and previously treated aneurysms (P=0.6894). Overall, occlusion rate decreased by 14% with an increase of aneurysm size by 1 mm (P=0.0283). CONCLUSION: For anterior circulation aneurysms, the off-label application of PED is as effective and safe as reported for on-label intracranial aneurysms.
Aneurysm ; Carotid Artery, Internal ; Cohort Studies ; Female ; Headache ; Humans ; Hypertension ; Intracranial Aneurysm ; Male ; Retrospective Studies ; Smoke ; Smoking

BACKGROUND:Network medical research contains various widely applicable networks with different structures, and construction methods. These networks are not organized in architecture yet, and there is a lack of overview about its application and research progress. OBJECTIVE:To organize various medical networks to a hierarchical architecture, and summarize their research progress. METHODS:A computer-based search of CNKI and PubMed databases was performed for articles about the network medicine published between 1999 and 2016 using the keywords ofdisease network, protein interaction network, metabolic network, gene regulatoryin English and Chinese, respectively. Then the main research contents, module property, construction methods, maturity and application progress of network medicine were discussed to predict the research direction. RESULTS AND CONCLUSION:The architecture of network medicine consists of molecular interaction network layer (interactome), disease network layer (diseasome) and drug network layer (drugome). In the interactome, protein-protein interaction network, metabolic network and gene regulatory network are in the order of organisms → mammals →human, and respective networks of human have been mapped but not mature;and new networks are being built. In diseasome, many disease networks have been constructed using a single element to cluster;and cluster by new element or combined elements can be considered in the future. Given this the current pharmacology is based on protein, there are few networks in the drugome the elements that constitute the drugome are only drug and protein.

BACKGROUND: The proliferation of peripheral blood stem cells among peripheral blood mononuclear cells (PBMCs) invitro remains unclear. There is no optimal marker for tracing PBMCs transplanted in vivo.OBJECTIVE: To observe the degree of PBMC proliferation in stem cell medium by EdU labeling and to explore thefeasibility of EdU-labeled peripheral blood stem cells.METHODS: New Zealand rabbit PBMCs were isolated and cultured for 1 to 5 days in stem cell medium supplementedwith EdU. The cells were observed and counted at 0, 1, 2, 3, 4 and 5 days in culture. The cells were harvested at eachtime point and stained with EdU fluorescent reagents. Then, confocal microscopy and flow cytometry were used to detectEdU-labeled cells.RESULTS AND CONCLUSION: (1) Freshly isolated rabbit PBMCs were rounded and showed clear outline. After 1 dayculture, most of the cells were suspended in the medium, spherical or round. There were also a few cell clusters andadherent cells scattered in a triangle or polygon shape; after 2 days culture, more cell debris were observed, and mostcells were round; when cultured for 3-5 days, increased cell debris, smaller cell mass and decreased cell densitysignificantly were observed. (2) With the prolongation of culture time, the cell count decreased gradually. (3) Whencultured for 1 day, EdU labeled cells in red were scattered. The number of cells marked with EdU red label increasedsignificantly at day 2 and remained unchanged after 3 days of culture. At 5 days of culture, the number of red cellsmarkedly decreased; the highest positive rate of EdU-labeled cells was (2.38±0.10)% at 2 days after culture. To conclude,these results showed that the proportion of proliferating cells in rabbit PBMCs was very low. EdU is capable of labelingproliferative cells among PBMCs.