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Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)( n =25)and a gastric cancer(GC) group(only immunotherapy)( n =26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and β diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group( P =0.035).The dry mouth( P =0.038)and altered taste( P =0.008)were mitigated in the WD-3 group after treatment,and the reflux( P =0.001)and dry mouth( P =0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia( P =0.047)and dry mouth( P =0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival( P =0.039, P =0.043).The α and β diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P >0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes ( P =0.038, P =0.042)and higher relative abundance of Proteobacteria ( P =0.016, P =0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group( P =0.035)and the WD-3 group( P =0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P <0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level, Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group( P =0.037, P =0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.

To observe the effect of Xiaoqinglong decoction combined with noninvasive ventilation on procalcitonin (PCT), blood gas analysis and respiratory functions in acute exacerbation of chronic obstructive pulmonary disease in the elderly (AECOPD), and investigate its correlation and clinical significance. Eighty-four elderly AECOPD patients with respiratory failure in our hospital from January 2015 to October 2017, were randomly divided into control group and observation group, 42 cases in each group. The control group received western medicine combined with noninvasive ventilator therapy, and the patients in observation group additionally received Xiaoqinglong decoction on the basis of the treatment in control group. Both groups were treated for 2 weeks. The clinical effects of two groups were observed and their PCT, blood gas analysis outcomes [arterial oxygen partial pressure (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), respiratory function, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC], TCM syndrome score and other indexes and adverse reactions were compared before and after treatment. The total efficiency was 95.24% (40/42) in observation group, higher than 76.19% (32/42) in control group, with statistically significant difference ( P <0.05). There were no statistically significant differences in PCT, PaO₂, PaCO₂, FVC, FEV1/FVC, FEV1, and TCM syndrome scores between two groups before treatment. But after treatment, PCT and PaCO₂ levels in the observation group were lower and PaO₂, FVC, FEV1/FVC, FEV1 levels was higher than those in the control group ( P <0.05); TCM syndrome scores were lower than those in the control group ( P <0.05); both groups had no obvious adverse reactions. The results showed that Xiaoqinglong decoction combined with noninvasive ventilator could significantly reduce the procalcitonin level, effectively improve the respiratory function and blood gas analysis indexes, and significantly reduce the clinical symptoms in AECOPD patients, so it is worthy of promotion., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

It is very important to identify nitrate sources in reservoirs that serve as high quality water sources to control its eutrophication. Stable isotopes (δ 15 N and δ 18 O) and a Bayesian model (stable isotope analysis in R, SIAR) were applied to identify nitrate sources and estimate the proportional contributions of multiple nitrate sources in four reservoirs (Qingshan reservoir, Duihekou reservoir, Siling reservoir, and Lifan reservoir) that serve as sources of drinking water in the Hangjiahu area, one of the most densely populated and most quickly developing areas in East China. It was shown that nitrogen pollution, which was dominated by nitrate (NO 3 - ), existed in the four reservoirs. Greater human activities caused more nitrogen pollution (average NO 3 - concentration 0.21 mmol ·L -1 ) in the Qingshan reservoir. A significant positive correlation ( P <0.01) was observed between Cl - and NO 3 - . The analysis of the water in the Duihekou reservoir, Siling reservoir, and Lifan reservoir, with lower Cl - concentrations and higher NO 3 - /Cl - ratios, suggested that chemical fertilizer was the main source, while the analysis of the water in the Qingshan reservoir, with medium Cl - concentrations and NO 3 - /Cl - ratios, indicated a mixture of NO 3 - sources. The δ 15 N ranged from 0.9‰ to 7.2‰, and the δ 18 O ranged from 2.8‰ to 14.1‰ in the four reservoirs. The δ 18 O values in more than 86% of the water samples were less than 10‰, and the δ 15 N/δ 18 O values in 93% of the water samples were less than 1.3. It was identified that nitrification rather than denitrification acted as the primary N cycling process in the four reservoirs. SIAR was used to estimate the proportional contribution of five NO 3 - sources (industrial wastewater, sewage/manure, chemical fertilizer, soil nitrogen, and precipitation) in the Qingshan reservoir and of three NO 3 - sources (chemical fertilizer, soil nitrogen, and precipitation) in the Duihekou reservoir, Siling reservoir, and Lifan reservoir. The source apportionment results showed that chemical fertilizers and soil nitrogen were the dominant nitrate sources and their contributions were 75%-82%. It was revealed that nitrogen pollution in the water source reservoir caused by cropping non-point source pollution was very serious. Nitrate source contributions in Qingshan reservoir also included sewage/manure (25%), soil nitrogen (7%), and precipitation (6%), indicating that nitrogen pollution by sewage/manure should not be ignored in the higher human activity areas. The nitrate source in the Duihekou reservoir, Siling reservoir, and Lifan reservoir also included precipitation, with the nitrate contribution from precipitation at 21%, 24%, and 15%, respectively. It was suggested that precipitation contributed more nitrate to the water in areas with less human activity.