Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Objective:To investigate the mechanism of Yunshi Ganmao Heji against respiratory syncytial virus (RSV) infection based on network pharmacology and in vivo experiments. Methods:Network pharmacological prediction: Several databases including TCMSP and GeneCards were used to predict the active ingredients and targets of Yunshi Ganmao Heji in the intervention of RSV infection. Cytoscape 3.2.1 software was used to construct the traditional Chinese medicine component-disease target network diagram. The interactions between proteins were analyzed by STRING database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using Metascape database. Molecular docking technology was used to verify the results of network pharmacology. Experimental verification of Yunshi Ganmao Heji for the intervention of RSV infection: A mouse model of RSV infection was established through intranasal infection. After the administration of Yunshi Ganmao Heji, blood routine test results, lung indexes and pathological changes in lung tissue were analyzed. Peripheral blood T cell subsets were detected by flow cytometry. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA. RT-PCR was used to detect the relative expression of TLR4, NF-κB and RSV-N gene at mRNA level in lung tissues.Results:A total of 41 active ingredients of Yunshi Ganmao Heji and 111 drug targets for RSV infection were obtained. Besides, 167 signaling pathways mainly including PI3K/AKT, MAPK and Toll-like receptor signaling pathways were obtained. Molecular docking results showed that the binding energies of luteotin, kaempferol and quercetin, three active ingredients of Yunshi Ganmao Heji, with RSV-G, RSV-F, PI3K, AKT1 and Bcl-2 were less than 0 kcal/mol. In vivo experiment results showed that compared with RSV group, the counts of white blood cells and lymphocytes increased and the lung index decreased in high-dose Yunshi Ganmao Heji group, with statistically significant difference ( P<0.05). HE staining showed pulmonary hyperplasia, thickened alveolar wall and inflammatory cell infiltration in interstitium in RSV group. Alveoli in ribavirin group as well as low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups tended to be of uniform size, and the alveolar walls was roughly uniform in thickness. Compared with RSV group, the low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups showed significantly increased numbers of CD3 +, CD4 + and CD8 + T lymphocytes, decreased CD4 + /CD8 + T cell ratio, lower levels of TNF-α, IL-6, IL-1β in serum, and reduced viral load and inhibited expression of TLR4 and NF-κB at mRNA level in lung tissues ( P<0.05). Conclusions:Yunshi Ganmao Heji can regulate RSV infection by targeting multiple targets and pathways with several active ingredients. Its main functions are to alleviate pathological injury in lung tissues and reduce inflammatory response, and the possible mechanism underlying the antiviral functions may be related to its inhibitory effect on the activation of TLR4/NF-κB pathway.

Objective:To investigate the predictive value of inflammatory and nutritional indices for postoperative survival of elderly patients with esophageal squamous carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 130 elderly patients with esophageal squamous carcinoma who were admitted to Sichuan Cancer Hospital from January 2019 to April 2020 were collected. There were 102 males and 28 females, aged (70±4)years. Mea-surement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Receiver opera-ting characteristic (ROC) curves were plotted. The area under the curve (AUC) and optimal cut-off values were calculated. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Postoperative survival of elderly patients with esophageal squamous carcinoma predicted by inflammatory and multitional indices. Results of ROC curves analysis showed that the best cut-off values of preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI) for predicting postoperative survival of elderly patients with esophageal squamous carcinoma were 470.71×10 9/L, 1.11, 2.07, 136.24, and 46.28, respectively. (2) Risk factors analysis of postoperative survival of elderly patients with esophageal squamous carcinoma. Results of multivariate analysis showed that preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI<46.28, score of preoperative patient-generated subjective global assessment (PG-SGA) ≥4, postoperative pathological stage Ⅳ and post-operative complications were independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma ( hazard ratio=3.30, 2.50, 0.36, 4.86, 1.57, 1.97, 95% confidence interval as 1.10?9.88, 1.07?5.88, 0.16?0.81, 1.13?20.87, 1.20?2.06, 1.02?3.82, P<0.05). (3) Follow-up. All the 130 patients were followed up for 39(range, 1?60)months. Of the 130 patients, 81 cases survived, 49 cases died, and the median overall survival time was not reached. The 1- and 3-year survival rates of the 130 patients were 83.85% and 54.62%, respectively. ① The median overall survival time was 25(0,43)months for patients with SII ≥470.71×10 9/L, and unreached for patients with SII <470.71×10 9/L, showing a significant difference between them ( χ2=60.59, P<0.05). ② The median overall survival time was 26(0,44)months for patients with SIRI ≥1.11, and unreached for patients with SIRI <1.11, showing a significant difference between them ( χ2=45.57, P<0.05). ③ The median overall survival time was unreached for patients with PNI ≥46.28, and 38(0,47)months for patients with PNI <46.28, showing a significant difference between them ( χ2=12.53, P<0.05). ④ The median overall survival time was unreached for patients with PG-SGA <4 and ≥4, showing a signifi-cant difference between them ( χ2=14.41, P<0.05). ⑤ The median overall survival time was 25(1,47)months for patients in pathological stage Ⅲ, 12(1,32)months for patients in stage Ⅳ, and unreached for patients in stage 0, Ⅰ, Ⅱ, respectively, showing a significant difference among them ( χ2=58.75, P<0.05). ⑥ The median overall survival time was 33(1,47)months for patients with postoperative complication, and unreached for patients without postoperative complication, showing a significant difference between them ( χ2=14.27, P<0.05). Conclusions:Preoperative SII, SIRI and PNI have good predictive value for postoperative survival in elderly patients with esophageal squamous carcinoma. Preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI <46.28, score of preoperative PG-SGA ≥4, postoperative pathological stage Ⅳ, and postoperative complications are independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma. Patients with preoperative SII <470.71×10 9/L, preoperative SIRI <1.11, preoperative PNI >46.28, score of preoperative PG-SGA <4, postoperative pathological stage 0, Ⅰ, Ⅱ, and non post-operative complications have better survival.

Objective:To evaluate the adjuvant role of the eCura scoring system in selecting appropriate treatment strategies after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) patients.Methods:The clinicopathological data of 110 EGC patients who underwent non-curative ESD at Fujian Provincial Hospital from January 2015 to June 2019 were retrospectively analyzed. According to the eCura score, patients were divided into three lymph node metastasis (LNM) risk groups: low-risk group (79 cases), middle-risk group (22 cases), and high-risk group (9 cases). The receiver operator characteristic (ROC) curve analysis was used to test the diagnostic efficacy of eCura scoring system in predicting LNM. Logistic regression analysis was used to explore the influence of risk stratification of eCura scoring system on LNM. Kaplan-Meier method was used to evaluate cancer survival rate, which was then compared with log-rank test.Results:Thirty-five patients underwent additional standard surgery after ESD, including 22 in the low-risk group, 8 in the middle-risk group, and 5 in the high-risk group. Among them, 5 cases had LNM, including 1 case in the low-risk group and the middle-risk group respectively and 3 cases in the high-risk group. The area under the ROC curve was 0.857 (95% CI: 0.697-0.952, P=0.001), and when the cut-off value of the eCura score was set at 3, the Yuden index reached the maximum value of 0.7, with the corresponding sensitivity and specificity of 80% and 90%, respectively. Logistic regression analysis showed that the probability of LNM in the middle-risk group was about 3.00 times (95% CI: 0.17-54.57, P=0.458) as high as that in the low-risk group, and the probability of LNM in the high-risk group was about 31.50 times (95% CI: 2.14-463.14, P=0.012) of that in the low-risk group. The follow-up time was 12 to 58 months, and the median follow-up time was 40 months. There were 10 cases of recurrence, including 4 cases in the low-risk group, 3 cases in the middle-risk group and 3 cases in the high-risk group, of which 2 cases in the low-risk group were from those of additional standard surgery after ESD, and the remaining 8 cases were from those who did not receive additional standard surgery after ESD. Kaplan-Meier survival curve analysis showed that the survival rate of patients with additional surgery in the low-risk group was similar to that of patients without ( P=0.319), and the survival rate of patients with additional surgery in the middle-risk group was also similar to that of patients without ( P=0.296). The survival rate of patients with additional surgery in the high-risk group was significantly higher than that of those without ( P=0.013). Conclusion:The eCura scoring system can assist the selection of treatment strategies after non-curative resection of EGC, and can accurately predict the risk of subsequent LNM and recurrence. Close follow-up may be an acceptable option for patients with low risk of LNM, and additional standard surgical treatment may be more conducive to improving the prognosis in patients with high risk of LNM.

The standardization of pediatric Tuina is beneficial to pediatric Tuina practitioners in a norm practices. The paper collects the content from teaching textbooks, TCM ancient books and database literature, and tries to develop the technical specifications of pediatric Tuina by four rounds Delphi surveys and expert consensus. This specification covers the manipulation of pediatric Tuina, the position of acupoints, the effects of acupoints and the diagnosis and treatment of pediatric Tuina, including indications, contraindications, cautious use, operation steps and methods.

Objective:To evaluate the safety and long-term efficacy of endoscopic resection of gastric stromal tumors with a diameter of >2-4 cm.Methods:The clinical data of 307 patients, who underwent endoscopic or surgical resection and pathologically confirmed to be gastric stromal tumors with a diameter ≤4 cm in Fujian Provincial Hospital, Jinshan Branch of Fujian Provincial Hospital or Fujian Geriatric Hospital from January 2014 to December 2019, were collected. The propensity score matching (1∶1) was performed for the cases with the tumor size of >2-4 cm.Then the incidence of adverse events related to the operation and clinical outcomes were compared between 41 patients in the endoscopic group and 41 patients in the surgical group.Results:Compared with the surgical group, the median operation time in the endoscopic group was significantly shorter (58.0 min VS 108.0 min, Z=-4.789, P<0.001), and the median hospitalization cost was significantly lower (22.7 thousand yuan VS 42.0 thousand yuan, Z=-7.164, P<0.001). There were no significant differences in postoperative fasting time or postoperative hospitalization time between the two groups ( P>0.05). Complications occurred in 7 cases (17.1%) in the endoscopy group, including 5 cases of postoperative acute infection, 1 case of postoperative perforation, and 1 case of postoperative bleeding; all 9 cases (22.0%) in the surgical group developed postoperative acute infection. There was no significant difference in the overall incidence of complications between the two groups ( χ2=0.311, P=0.577). Tumors in both groups were completely removed with negative resection margins. The follow-up time of the endoscopy group was 34.3±15.6 months, and that of the surgical group was 42.2±20.2 months. No recurrence or distant metastasis was observed during the follow-up period in the two groups. Conclusion:Endoscopic resection of large gastric stromal tumor (range>2-4 cm) is safe and effective in the long term, which can be used as one of the methods for gastrointestinal stromal tumors.

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.

Objective:To discuss the value of ultrasound in the diagnosis of pelvic lipomatosis and analyze the causes of misdiagnosis.Methods:A retrospective analysis of 68 cases of pelvic lipomatosis confirmed by operation or imaging in Peking Union Medical College Hospital from January 2000 to December 2018 was made to summarize the characteristics of ultrasonic manifestations.Results:Ultrasonographic findings were as follows: 6 cases (8.8%) had increased fat-like hyperecho in pelvic cavity; 60 cases (88.2%) had abnormal bladder; 42 cases (61.7%) had pyelectasis and 24 cases (35.3%) had ureterectasis. Of the 68 cases, 6 cases (8.8%) were correctly diagnosed; 54 cases (79.4%) were missed; 8 cases (11.8%) were misdiagnosed, including 7 cases (10.3%) of bladder tumor and 1 case (1.5%) of retroperitoneal giant mass.Conclusions:Pelvic lipomatosis has characteristic sonographic features.When urinary tract obstruction and bladder wall thickening are observed, pelvic lipomatosis should be considered. Bladder shape and existence of increasing fat-like hyperecho in the pelvis should be further scanned to reduce the misdiagnosis rate of pelvic lipomatosis.

Objective To analyze the possible risk factors of IVIG non-response of Kawasaki disease (KD),Shanghai Children's Hospital and Shanghai Junze Software develop an research platform,which is based on E-Science model.Through the mathematical model by integrating the risk factors to explore the method of effective prediction for IVIG non-response,and to provide the clinical basis for timely and effective treatment and prognosis of the disease.Methods The data of KD children who were hospitalized in Shanghai Children's Hospital from January 2013 to November 2016 were included.The indexes included gender,age,time of IVIG treatment,and laboratory examinations.The multivariate logistic regression was used to analyze the influencing factors of IVIG non-response.The indexes in the model were deduced according to the independent variables of the logistic regression equation.The ROC curve and the area under the curve were calculated for the new prediction model.The sensitivity and specificity of the new prediction model were calculated according to the cutoff value.Finally,the new model was compared with the Kobayashi and Egami scoring model.Results The levels of CRP,NLR,LDH,ALB and FDP in children with KD were influencing factors for IVIG nonresponse (P ＜ 0.05).According to the logistic regression equation,the sensitivity and specificity of the model used to predict IVIG non-response were 69.7％ and 80.4％,respectively,and the area under the ROC curve was 0.825 (95％ CI:0.769-0.882).Kobayashi and Egami scoring models were tested,the sensitivity and specificity of the new scoring system were better than previous ones.Condusion The scoring model established in this study has a good effect in predicting IVIG non-response in KD patients and could be used in clinical practice,and it is worthy to be validated and adjusted by large-scale data.

Phenol-soluble modulins (PSMs) are a novel family of small amphipathic, alpha-heli-cal peptides with strong surfactant-like properties. PSMs have multiple roles in staphylococcal pathogenesis and are considered as important virulence-associated factors. They may cause lysis of many eukaryotic cells, such as human neutrophils,erythrocytes and dendritic cells;induce the expression of pro-inflammatory cyto-kines;facilitate the structuring and detachment of biofilms;influence the expression of other genes. This re-view summarizes the classification,structure,regulatory effect on gene expression and biological function of PSMs. The potential avenues to target PSMs for drug development against staphylococcal infections are also evaluated in this paper.