Objective To investigate the effect and mechanism of osteopontin(OPN)in hepatoma cell migration through galectin-3 binding protein(LGALS3BP).Methods Human hepatoma cell lines SMMC-7721,SMMC-P(stably transfected with empty eukaryotic expression vectors),and SMMC-OPN(stably transfected with the OPN gene)were cultured.mRNA expression levels of OPN and LGALS3BP were measured by RT-qPCR.Western blot assays were used to analyze the relative protein expression of OPN and LGALS3BP and PI3K/AKT pathway.Wound healing assays were performed to explore the cell migration ability.After transfection with LGALS3BP-targeting small interfering RNA(si-LGALS3BP)or negative control small RNA(si-NC)into SMMC-OPN cells,cell migration and relative expression of PI3K/AKT pathway-related proteins were assessed.Results Compared with SMMC-7721 and SMMC-P,the migratory ability of SMMC-OPN cells was significantly reinforced,and expression of LGALS3BP was obviously upregulated at both mRNA and protein levels.Moreover,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins was significantly increased.Wound healing assays showed that the si-LGALS3BP obviously suppressed the migratory ability of SMMC-OPN cells.Furthermore,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins in SMMC-OPN cells was significantly decreased after transfection of si-LGALS3BP.Conclusions OPN activates the PI3K/AKT pathway by upregulating LGALS3BP expression to promote hepatoma cell migration.

Objective To systematically evaluate the clinical efficacy of treatment based on intestine in the sepsis induced acute lung injury/acute respiratory distress syndrome(ALI/ARDS)under the traditional Chinese medicine theory"interior and exterior relationship between the lung and large intestine",and to provide evidence-based reference for clinical practice.Methods A computerized search of CNKI,Wanfang database,VIP database,China Biology Medicine disc(CBMdisc),Embase database of Dutch medical abstracts,PubMed database,Cochrane library database was performed to identify randomized controlled trial(RCT)that used the Tongfu method as an intervention for the treatment of ALI/ARDS induced by sepsis,published from the database establishment until October 8,2020.The control group was treated with conventional western medicine,and the test group was treated with the combination of Tongfu method and conventional western medicine.Screening of the literature and data extraction for those that met the inclusion criteria were performed by 2 investigators.The modified Jadad scale was used for quality assessment,and RevMan 5.4 and Stata 16.0 software were used for Meta analysis of the data.Results Thirteen articles were finally included,all of which were single center RCT studies,including 7 articles with≥4 points and 6 articles with<4 points.A total of 579 patients were included,290 in the test group and 289 in the control group.Meta-analysis showed that combined Tongfu treatment significantly increased the ALI/ARDS patient caused by sepsis oxygenation index[PaO2/FiO2;mean difference(MD)= 62.55,95%confidence interval(95%CI)was 55.74 to 69.37,P<0.05],reduced the levels of interleukin-6(IL-6;MD =-29.70,95%CIwas-48.34 to-11.06,P<0.05),tumor necrosis factor-α(TNF-α;MD=-2.94,95%CIwas-5.28 to-0.59,P<0.05),procalcitonin(PCT;MD =-1.34,95%CI =-2.17 to-0.51,P<0.05)and C-reactive protein(CRP;MD =-22.41,95%CIwas-36.52 to-8.29,P<0.05),reduced mechanical ventilation time(MD=-2.26,95%CIwas-2.86 to-1.66,P<0.05)and hospitalization time in intensive care unit(ICU;MD=-4.15,95%CIwas-7.47 to-0.84,P<0.05),reduced the 28-day mortality[relative risk(RR)= 0.43,95%CI was 0.24 to 0.76,P<0.05]and acute physiology and chronic health status scoreⅡ(APACHEⅡ;MD =-3.53,95%CI was-5.41 to-1.64,P<0.05).Conclusion Treatment based on intestine is valuable for reducing the condition and improving the prognosis of ALI/ARDS patients caused by sepsis,but further high-quality RCT studies are still needed to verify its efficacy and provide more accurate evidence-based evidence for clinical treatment.

Objective:To investigate the influencing factors of refractory anastomotic stenosis after laparoscopic intersphincteric resection (Ls-ISR) for rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 495 patients who underwent Ls-ISR for rectal cancer in two medical centers, including 448 patients in Peking University First Hospital and 47 patients in Cancer Hospital Chinese Academy of Medical Sciences, from June 2012 to December 2021 were collected. There were 311 males and 184 females, aged 61 (range, 20-84)years. Observation indicators: (1) incidence of anastomotic stenosis; (2) influencing factors of refractory anastomotic stenosis after Ls-ISR; (3) construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of postoperative anastomotic leakage and anastomotic stenosis up to August 2022. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. Factors with P<0.10 in univariate analysis were included in multivariate analysis. The R software (3.6.3 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of nomogram prediction model. Results:(1) Incidence of anastomotic stenosis. All 495 patients underwent Ls-ISR successfully, without conversion to laparotomy, and all patients were followed up for 47(range, 8-116)months. During the follow-up period, there were 458 patients without anas-tomotic stenosis, and 37 patients with anastomotic stenosis. Of the 37 patients, there were 15 cases with grade A anastomotic stenosis, 3 cases with grade B anastomotic stenosis and 19 cases with grade C anastomotic stenosis, including 22 cases being identified as the refractory anastomotic stenosis. Fifteen patients with grade A anastomotic stenosis were relieved after anal dilation treat-ment. Three patients with grade B anastomotic stenosis were improved after balloon dilation and endoscopic treatment. Nineteen patients with grade C anastomotic stenosis underwent permanent stoma. During the follow-up period, there were 42 cases with anastomotic leakage including 17 cases combined with refractory anastomotic stenosis, and 453 cases without anastomotic leakage including 5 cases with refractory anastomotic stenosis. There was a significant difference in the refractory anastomotic stenosis between patients with and without anastomotic leakage ( χ2=131.181, P<0.05). (2) Influencing factors of refractory anastomotic stenosis after Ls-ISR. Results of multivariate analysis showed that neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage were independent risk factors of refractory anastomotic stenosis after Ls-ISR ( hazard ratio=7.297, 3.898, 2.672, 95% confidence interval as 2.870-18.550, 1.050-14.465, 1.064-6.712, P<0.05). (3) Construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Based on the results of multivariate analysis, neoadjuvant therapy, distance from tumor to anal margin and clinic N staging were included to constructed the nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Results of ROC curve showed the AUC of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR was 0.739 (95% confidence interval as 0.646-0.833). Conclusions:Neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage are independent risk factors of refractory anastomotic stenosis after Ls-ISR. Nomogram prediction model based on these factors can predict the incidence of refractory anastomotic stenosis after Ls-ISR.

Objective:To analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).Methods:The clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.Results:A total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.Conclusions:The primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.

Objective:To evaluate the clinical efficacy and safety of combination of traditional Chinese and Western medicine in the treatment of coronavirus disease 2019 (COVID-19) by Meta analysis.Methods:The clinical randomized controlled trials (RCT) and cohort studies on the treatment of COVID-19 with combination of Chinese traditional and Western medicine published on CNKI, Wanfang database, VIP database and PubMed were searched by computer from January 2020 to June 2020. Patients in the simple Western medicine treatment group were treated with routine treatment of Western medicine, and the patients in integrated traditional Chinese and Western medicine treatment group were treated with traditional Chinese medicine on the basis of routine treatment of Western medicine. The main outcome was the total effective rate of treatment. The secondary outcome were the antipyretic rate, chest CT recovery rate, lymphocyte count (LYM), C-reactive protein (CRP) level and safety. The Cochrane manual and the Newcastle Ottawa Scale (NOS) were used to evaluate the quality of the literature; the RevMan5.3 software was used to analyze the articles that meets the quality standards, and a funnel chart was drawn to evaluate the total effective publication bias.Results:Thirteen articles were analyzed, including 1 039 COVID-19 patients, 559 in integrated traditional Chinese and Western medicine treatment group and 480 in simple Western medicine treatment group. The results of Meta-analysis showed that compared with the simple Western medicine treatment group, the combination of routine treatment of Western medicine and traditional Chinese medicine Qingfei Paidu decoction, Lianhua Qingwen granule, Shufeng jiedu capsule, Xuebijing injection or Reyanning mixture could significantly improve the total effective rate, antipyretic rate and chest CT recovery rate [total effective rate: odds ratio ( OR) = 2.95, 95% confidence interval (95% CI) was 2.10-4.14, P < 0.000 01; antipyretic rate: OR =3.01, 95% CI was 1.64-5.53, P = 0.000 4; chest CT recovery rate: OR = 2.53, 95% CI was 1.83-3.51, P = 0.000 1], increase LYM levels [mean difference ( MD) = 0.26, 95% CI was 0.02-0.50, P = 0.03], and reduce of CRP content ( MD = -17.68, 95% CI was -33.14 to -2.22, P = 0.02). Based on the funnel chart analysis of 12 articles with total efficiency, the result showed that the funnel chart distribution was not completely symmetrical, indicating that there might be publication bias. Conclusions:On the basis of routine treatment with Western medicine, combined with traditional Chinese medicine can significantly improve the total effective rate of COVID-19 and improve the laboratory results and clinical symptoms of patients. Compared with the routine treatment of Western medicine alone, the combination of traditional Chinese and Western medicine has better clinical efficacy and safety.

Objective:To analyze the data of Chinese medicine prescriptions for the treatment of coronavirus disease 2019 (COVID-19) in Shijiazhuang City, Hebei Province, with a view to further guide the clinical use of Chinese medicine in the prevention and treatment of COVID-19.Methods:Forty-eight patients diagnosed with COVID-19 who were treated by critical care team of Hebei Traditional Chinese Medicine Hospital in the intensive care unit (ICU) of Hebei Chest Hospital (Hebei Provincial COVID-19 designated hospital) from January 7 to March 4, 2021, were enrolled in this study. The patients' gender, age, clinical classification, past history, and all Chinese medicine prescriptions for the first visit and follow-up visits during the hospitalization were collected. A database was established based on the Ancient and Modern Medical Records Cloud Platform (V2.2.1), and the methods of frequency analysis, correlation analysis, cluster analysis, and complex network analysis were used to analyze the prescriptions of traditional Chinese medicine.Results:Among the 48 patients with COVID-19, 20 were males and 28 were females; the average age was (62.4±13.7) years old. The patients' condition was generally severe, including 17 cases of common type, 25 cases of severe type, and 6 cases of critical type, most of whom were combined with hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease and other basic illnesses. A total of 146 valid prescriptions were included, involving 59 prescriptions and 115 Chinese medicines. Frequency analysis of 146 prescriptions showed that the commonly used prescriptions for patients with COVID-19 were Qingfei Paidu decoction (30 times, 20.55%), Xuanbai Chengqi decoction (10 times, 6.85%), and Dayuan Yin (10 times, 6.85%). The common Chinese medicines were liquorice (80 times, 54.79%), tuckahoe (76 times, 52.05%), gypsum (70 times, 47.95%), bitter almond (70 times, 47.95%), ephedra (57 times, 39.04%), scutellaria (56 times, 38.36%), tangerine peel (53 times, 36.30%), patchouli (50 times, 34.25%), atractylodes macrocephala (50 times, 34.25%), and bupleurum (43 times, 29.45%). The main effects were clearing heat and detoxification (129 times), clearing heat-fire (129 times) and eliminating dampness and diuresis (110 times). The medicinal properties were mainly warm (509 times), flat (287 times), and cold (235 times). The medicinal tastes were mainly pungent (765 times), sweet (654 times), and bitter (626 times). The medicinal channel tropism were mainly lung (1 096 times), spleen (785 times), and stomach (687 times). The correlation analysis showed that there were 17 drug combinations in total, among which the top 3 drug pairs in support were bitter almond-gypsum (0.43), ephedra-bitter almond (0.38), tangerine peel-poria (0.36), and ephedra-gypsum (0.36). Cluster analysis showed that there were 3 groups of clustering formulas. The first group was ephedra, bitter almond, and gypsum. The second group was patchouli, tuckahoe, tangerine peel, and atractylodes macrocephala. The third group was scutellaria, licorice, immature orange fruit, oriental waterplantain rhizome, bupleurum, ginger, and cassia twig. The core drugs were composed of tuckahoe, bupleurum, tangerine peel, atractylodes macrocephala, patchouli, bitter almond, scutellaria, gypsum, ephedra, and licorice.Conclusions:Middle-aged and elderly patients with COVID-19 are accompanied by Qi deficiency and internal invasion of toxins, and the pathogenesis evolves rapidly. Damp and turbid toxins often block the lungs and trap the spleen, leading to disorder of Qi movement, and even invaginate Ying and Xue, drain Yin and Yang. The treatment is based on removing turbidity and detoxification, and replenishing Qi and nourishing Yin are the principle treatments, so that the evil is eliminated and the Qi is restored.

2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.

Objective To observe the clinical curative effects of Changwei Shu combined with conventional western medicine therapy in treating the sepsis patients with gastrointestinal dysfunction.Methods A total of 120 cases of sepsis patients with gastrointestinal dysfunction were randomly divided into treatment group and control group,60 patients in each group.The control group was given conventional western medicine therapy,and the treatment group was given Changwei Shu combined with conventional western medicine therapy.After treatment for 7 days,the clinical efficacy and safety were evaluated by observing the changes in white blood cell (WBC) count,procalcitonin (PCT) level,intra-abdominal pressure (IAP),gastrointestinal dysfunction scores,and scores of acute physiology and chronic health evaluation (APACHE Ⅱ).Results (1) For one case dropped out and one was excluded from the treatment group,and 4 cases dropped out and 2 were excluded from the control group,a total of 58 cases in the treatment group and 54 in the control group were included into the study at the end of the trial.(2) The total effective rate of the treatment group was 91.38％ and that of the control group was 88.89％,the difference being significant (P ＜ 0.05).(3) After treatment,WBC count,PCT level and IAP of the two groups were improved (P ＜ 0.01 compared with those before treatment),and the improvement of the treatment group was superior to that of the control group (P ＜ 0.01).(4) After treatment,gastrointestinal dysfunction scores and APACHE Ⅱ scores of the two groups were decreased(P ＜ 0.01 compared with those before treatment),and the decrease of the treatment group was superior to that of the control group (P ＜ 0.01).(5) During the treatment,4 cases from the treatment group had nausea,and 5 cases from the control group had nausea and abdominal distention,and the symptoms disappeared spontaneously one week later.No obvious changes were found in the hepatic and renal function of the two groups.Conclusion Changwei Shu exerts an effect on reducing the inflammation,improving the gastrointestinal function,and relieving the illness severity of sepsis patients with gastrointestinal dysfunction.

ObjectiveTo study the anti-inflammatory effect of traditional Chinese medicine (TCM) Changweishu on sepsis patients with gastrointestinal dysfunction and its protective effect on intestinal mechanical barrier.Methods A prospective research method was conducted. Fifty sepsis patients with gastrointestinal dysfunction admitted into Department of Emergency Intensive Care Unit (EICU) of Hebei Provincial TCM Hospital from October 2013 to June 2015 were enrolled, and they were divided into a conventional treatment of western medicine control group and a TCM Changweishu group according to the random number table method, 25 cases in each group. The conventional western medicine treatment was given to both groups, and in TCM Changweishu group, additionally Changweishu 1 dose per day, a mixture of following ingredients constituting one dose without decoction, was applied, including: rhubarb 9 g, dandelion 20 g, green tangerine peel 15 g, angelica sinensis radix 15 g, red and white peony each 12 g, rhizome ligusticum 9 g, agrimony 20 g, coptidis rhizoma 6 g, rhizoma pinelliae 6 g, fructus trichosanthis 15 g, garden burnet root 20 g, poria 20 g, and taken once 1/2 dose in the morning and once 1/2 dose in the evening by oral or nasal feeding. After treatment for 7 days, the level changes of inflammatory factors of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), high mobility group protein B1 (HMGB1) and gastrointestinal dysfunction indexes of diamine oxidase (DAO), D-lactic acid in the two groups were observed.Results After treatment, the levels of TNF-α, IL-6, HMGB-1, DAO, D-lactic acid in the two groups were significantly lower than those before treatment [the western medicine control group: TNF-α (A value) 10.89±1.65 vs. 50.30± 1.58, IL-6 (A value) 7.35±1.85 vs. 12.66 ± 1.43, HMGB1 (A value) 5.28 ±1.64 vs. 6.23±0.95, DAO (A value) 5.87±0.59 vs. 6.67±0.49, D-lactic acid (A value) was 2.63±0.17 vs. 4.58±0.16; TCM changweishu group: TNF -α (A value) 5.38±1.19 vs. 51.23±2.34, IL-6 (A value) 5.54±1.26 vs. 13.24±1.78, HMGB1 (A value) 3.69±1.09 vs. 6.14±1.42, DAO (A value) was 3.39± 0.40 vs. 6.70±0.34, D-lactic acid (A value) 1.95±0.13 vs. 4.63±0.11, allP < 0.05]. After treatment, the degrees of decline in indexes of TCM Changweishu group were more obvious than those in western medicine control group [TNF-α(A value) 5.38±1.19 vs. 10.89±1.65, IL-6 (A value) 5.54±1.26 vs. 7.35±1.85, HMGB1 (A value) 3.69 ±1.09 vs.5.28±1.64, DAO (A value) 3.93±0.40 vs. 5.87±0.59, D-lactic acid (A value) 1.95±0.13 vs. 2.63±0.17, allP <0.05].Conclusions TCM Changweishu has protective effect on sepsis patients with gastrointestinal dysfunction, and its mechanisms are the amelioration of damage in intestinal tract mechanical barrier, decrease of permeability of intestinal mucosa and inhibition of levels of inflammatory factors.

Objective:To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy.Me-thods:Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues.Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells,oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA)and CD24 antibody on CD24 expression,and the proliferation and tumorsphere formation capacity of these two cell lines.Results:CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05),as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05).CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05 ).Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05).Among them ATRA at least involved partially in the proliferation by down-regulating the CD24 expression (P<0.05 ),while CD24 antibody blocking had no effect on the CD24 expression.Conclusion:CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells.Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target.