OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.
Adenocarcinoma/pathology* ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

To implement the Guizhou Provincial Party Committee and the Provincial Government's strategic goal of building a"Chinese Hot Spring Province"in an all-round way, promote the development of Guizhou's"big health, big tourism, big poverty alleviation"and other industries, and enhance the development and utilization of Guizhou hot springs and their health and wellness value. With the support of the provincial Geological Prospecting Fund project Guizhou Province Physiotherapy Hot Springs(Geothermal Water)Survey and Evaluation, Guizhou Medical University was responsible for completing the topic"Study on the Physiotherapy Efficacy of Typical Hot Springs in Guizhou Province". Here, the background, study and design plan, quality control, and features and limitations of this project are briefly introduced.

Objective To investigate the effects of hot spring baths on blood pressure, resting heart rate, cardiovascular function related indicators and physical signs in population with high-normal blood pressure. Methods Residents of typical hot spring areas in Guizhou Province were included as the subjects. According to the epidemiological survey of the research group and the physical examination results before the intervention, combined with the inclusion and exclusion criteria, a total of 217 people with high normal blood pressure were selected as the observation subjects. The intervention of hot spring baths was carried out for four weeks, once time per day, 5 times per week, for 40-50 minutes each time. After the intervention, the blood pressure, resting heart rate and serum levels of creatine kinase(CK), lactate dehydrogenase(LDH), and α-hydroxybutyrate dehydrogenase(α-HBDH)were detected, and the improvement of cardiovascular related signs(palpitation, dizziness/headache, cough/sputum and night sweats)were clinically examined. SPSS 23.0 software was used for statistical analysis. Results Paired t-test results showed that the systolic blood pressure, diastolic blood pressure and resting heart rate of 217 high normal blood pressure subjects were significantly lower after hot spring baths(P < 0.01). Further analysis revealed that the number of people with high normal blood pressure dropped from 217 to 128 after the hot spring baths. Before the intervention, 95 of the 217 people with high-normal blood pressure had resting heart rates between 80 and 90 beats/min, and 35 of them above 90 beats/min. After the intervention, the resting heart rates of those above people decreased to 68 and 14, respectively. Serum levels of cardiovascular related indicators showed that CK, LDH, and α-HBDH levels in people with high-normal blood pressure decreased to some extent after the intervention, and CK level was significantly lower than that before the intervention(P < 0.05). The results of clinical examination showed that hot spring baths had a significant improvement effect on palpitation, dizziness/headache, cough/expectoration, and night sweats in people with high-normal blood pressure. Conclusion The typical hot spring baths in Guizhou Province can reduce the blood pressure and resting heart rate in population with high-normal blood pressure, and improve the cardiovascular function related indicators and physical signs to a certain extent.

Objective To explore the effect of typical hot spring bathing of Guizhou Province on dyslipidemia, which could provide scientific basis for clarifying the physiotherapy effect of hot springs. Methods The typical hot spring sites of three main types(hydrothermal hot spring, warm mineral hot spring and metasilicate hot spring)in Guizhou Province were selected as investigation sites. 189 residents with hyperlipidemia near the investigation sites were selected as subjects and were treated with hot spring baths for 4 weeks, once a day, 5 times a week and 40-50 minutes each time. The age and gender distribution of the subjects were obtained by a questionnaire. The levels of TC, TG, LDL-C and HDL-C in serum were measured by automatic biochemical analyzer at baseline and at the end of hot spring baths. The differences of the three kinds of hot spring baths on improvement rate of dyslipidemia, the changes of abnormal blood lipid indexes and their improvement rates were compared. Results After baths of hydrothermal hot springs, warm mineral hot springs and metasilicate hot springs, the improvement rates of abnormally elevated lipids were 15.6%, 40.4% and 47.9%, respectively. The improvement rates of abnormally elevated lipids after baths of warm mineral hot springs and metasilicate hot springs were significantly higher than that after hydrothermal spring baths(all P < 0.05). Compared with before hot spring bathing, the levels of TC, TG, LDL-C and non-HDL-C in serum significantly decreased in all three kinds of hot springs. Moreover, the degree of decrease of TG in serum and the improvement rate of abnormal TG after baths of warm mineral spring and metasilicate hot spring were significantly higher than that after hydrothermal spring baths. The degree of decrease of LDL-C in serum and the improvement rate of abnormal LDL-C after baths of metasilicate hot spring were significantly higher than that after baths of hydrothermal spring and warm mineral spring(all P < 0.05). Conclusion The three types of typical hot spring baths in Guizhou Province can mitigate the elevation of blood lipid. Compared with hydrothermal spring, warm mineral spring and metasilicate hot spring may have better improvement effect on blood lipid elevation due to their more significant improvement effect on abnormal elevation of TG and LDL-C in serum.

Objective To study the relieving effects of hot spring bath therapy on sleep quality for people with sleep disorders based on data from health bracelets. Methods After health examinations, 311 people with sleep disorders who participated in the bath therapy in five typical hot spring areas in Guizhou Province were selected as the subjects. A four-week hot spring bath therapy was implemented, and the bathing method and the classification of hot springs were the same as the"Overview of study of the physiotherapy efficacy of typical hot springs in Guizhou Province". The daily sleep time at night(minutes), deep sleep ratio(%), light sleep ratio(%)and rapid eye movement ratio(%)for all subjects were collected using the Huawei Honor Band 3 health bracelets. Repeated measures analysis of variance was used to compare the differences in sleep quality indicators of each group at night each week. The effect of three different hot spring bath therapies on the improvement of night sleep quality was evaluated by factor analysis. Results Hot spring bath therapy can increase night sleep time and deep sleep ratio, while reducing light sleep ratio. Compared with the first week, the night sleep time in the following three weeks significantly increased(P < 0.05), especially in the fourth week; the deep sleep ratio during the third and fourth weeks was significantly higher than during the first and second weeks(P < 0.05), but the light sleep ratio was lower than during the first and second weeks(P < 0.05). The rapid eye movement ratio did not change significantly throughout the 4 weeks(P > 0.05). Further classified according to the physiotherapy components of geological hot springs, the results showed that the water temperature type of hot springs can increase night sleep time and reduce light sleep ratio; the warm mineral type of hot springs has a certain regulatory effect on increasing night sleep time, deep sleep ratio and reducing light sleep ratio; the metasilicic acid type of hot springs can improve night sleep quality by increasing night sleep time and deep sleep ratio, while reducing light sleep ratio and rapid eye movement ratio. The factor analysis results suggest that the metasilicic acid type of hot springs is better than the water temperature type and warm mineral type of hot springs in improving night sleep quality. Conclusion Hot spring bath therapy can improve the night sleep quality for people with sleep disorders to varying degrees, and the metasilicic acid type of hot springs is relatively better than other types.

Objective To explore the improvement effect of typical hot spring bathing on sleep and anxiety and its correlation with serum melatonin level in Guizhou province. Methods Five typical characteristic hot springs in Guizhou were selected according to the geological type of hot spring water. A total of 226 residents in these areas were selected for the survey and the self-rating scale of sleep(SRSS)and the self-rating anxiety scale(SAS)were used to measure their scores before and after hot spring bathing, and the correlation between the changes of SRSS and SAS scores and the serum melatonin levels were analyzed. Results The SRSS and SAS scores of the respondents after hot spring bathing were lower than before, and the difference was statistically significant(P < 0.05). Serum melatonin levels after hot spring bathing were significantly higher than before(P < 0.05), and there was a negative correlation between the changes of SRSS and SAS scores and serum melatonin levels(P < 0.05). Conclusion Typical hot springs in Guizhou Province can significantly improve the sleep quality and anxiety state, which are related to the elevation of serum melatonin level.

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Objective To understand the influence of hot spring bathing intervention on population's antioxidation functions. Methods Three typical types of hot spring(metasilicic acid type, warm mineral type and temperature type)in Guizhou Province were selected for investigation. According to the inclusion-exclusion criteria, questionnaires and physical examinations results, 421 individuals were selected as observation subjects for hot spring bathing intervention, of which 311 subjects completed 40 to 50 minutes of intervention once a day, 5 days a week, and for 4 weeks. Two physical examinations before and after the intervention were conducted for the 311 subjects. The fasting venous blood samples on the mornings of two physical examinations were collected and the serum was separated. Levels of serum oxidative stress-related parameters including total superoxide dismutase(T-SOD), copper zinc superoxide dismutase(Cu-Zn SOD), glutathione sulfur transferases(GSTs)glutathione peroxidase(GSH-px), sulfhydryl(-SH)and malondialdehyde(MDA)were measured by enzymatical methods. Results The overall comparison showed that compared with before the bathing intervention, the levels of antioxidant enzymes including T-SOD, Cu-Zn SOD, GSTs and GSH-px significantly increased in serum after the intervention(all P < 0.05). There was an increasing trend of serum -SH level after the intervention, but with no statistical differences were seen(P > 0.05). MDA, a product of lipid peroxidation, significantly decreased in serum after the intervention(P < 0.05). The results of classified comparison showed that the effects of different hot spring types on antioxidant enzymes were different. Metasilicic acid type significantly increased the activities of GSTs and GSH-px in serum(all P < 0.05), warm mineral type significantly increased the activities of T-SOD and Cu-Zn SOD in serum(all P < 0.05), and temperature type significantly increased the activities of T-SOD, Cu-Zn SOD and GSTs in serum(all P < 0.05). There were increasing trends of serum -SH levels after bathing intervention of all three hot spring types, but no statistical differences were seen(all P > 0.05). The serum MDA levels decreased significantly after bathing intervention of all three types of hot springs(all P < 0.05). Conclusion Overall, bathing intervention of hot springs can improve the activities of antioxidant enzymes and reduce lipid peroxidation products in population. The results of oxidative stress parameters are slightly different in different types of hot springs. The subjects mainly show the elevation of glutathione related enzyme(GSTs and GSH-px)activities after intervention of metasilicic acid type, the elevation of superoxide dismutase(SOD)activities after intervention of warm mineral type and temperature type, and the decline of lipid peroxidation levels after intervention of all three types. It suggests that hot spring bathing may have certain effects on improving the body's antioxidation functions.

Objective:To explore the material basis and mechanism of Sangjiang Ganmao injection （SG） in the treatment of common cold by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） and network pharmacology. Method:UPLC-Q-Orbitrap HRMS was used to identify the chemical components of SG with mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-10 min， 4%-15%A； 10-35 min， 15%-30%A； 35-45 min， 30%-33%A； 45-55 min， 33%-60%A； 55-58 min， 60%A）， flow rate of 0.2 mL·min^-1， electrospray ionization （ESI） and scanning range of m/z 100-1 500 under positive and negative ion modes. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and GeneCards 5.0 database were used to screen and predict the potential targets of chemical components in SG， STRING 11.0 database and Cytoscape 3.7.2 software were used to construct protein-protein interaction （PPI） network model， gene ontology （GO） analysis and pathway analysis were performed on potential targets by Metascape 3.5， Reactome database and Kyoto Encyclopedia of Genes and Genomes （KEGG）， Cytoscape 3.7.2 software was used to build the network of "herbs-ingredients-key targets". Result:A total of 54 components in SG were identified， and 80 potential targets of SG for treatment of common cold were predicted and screened based on this. SG exerted therapeutic effects by acting on targets such as interleukin （IL）-6， tumor necrosis factor （TNF） and IL-10， and signaling pathways such as IL-17 signaling pathway， TNF signaling pathway and interaction of cytokine receptors. Conclusion:SG may interfere with the expression of inflammatory cytokines by acting on related targets and pathways such as inflammation and immune system， and regulate the immune function of the body as a whole， thereby exerting a therapeutic effect.