Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Application of scenario simulation teaching model of multimorbidity co-treatment in standardized training for general practice residents / 中华全科医师杂志

From February 1 to April 30, 2021, 48 general practice resident physicians in the First Affiliated Hospital of Naval Medical University were randomly divided into study group and control group with 24 in each group. The common comorbidities of the community-dwelling elderly, namely diabetes, diabetic retinopathy and osteoporosis were selected as teaching cases. The residents in control group received conventional teaching, while the scenario simulation teaching model of multicomorbity co-treatment was applied for the study group. The teaching effect, satisfaction and self-efficacy scores were compared between two groups. After training, the knowledge levels, the mastery of referral indicators and the performance of fundus ophthalmoscopy in the study group were significantly better than those in the control group ( t=2.27, 6.34, 4.09; P<0.05). They were (80.96±11.27) vs. (73.96±10.09), (10.33±2.41) vs. (6.38±1.88), (70.27±10.44) vs. (63.50±7.98), and students′ satisfaction and self-efficacy evaluation were higher than those of the observation group (all P<0.05). It is suggested that the simulation teaching of multi-disease co-treatment scenario is more beneficial than the traditional teaching to improve the comprehensive care ability of standardized training physicians in general practice for patients with chronic disease.

Mechanism of phlegm-stasis co-treatment for myocardial protection in rats with diabetes mellitus by regulating JNK signaling pathway / 国际中医中药杂志

Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.

Co-Treatment of Phlegm and Stasis Improves Myocardial Inflammation in Rats with Diabetes Mellitus via TLR4/NF-κB/IκB Pathway / 中国实验方剂学杂志

Objective:To observe the intervention of phlegm-stasis co-treatment on the myocardial Toll-like receptor 4 （TLR4）/nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）/nuclear factor-<italic>κ</italic>B inhibitor （I<italic>κ</italic>B） signaling pathway， and to investigate its mechanism in improving myocardial inflammation in rats with diabetes mellitus （DM）. Method:Forty-five male SD rats of SPF grade were randomly divided into a normal group， a phlegm-resolving （Xiao Xianxiongtang， 4.05 g·kg^-1） group， a stasis-resolving （Xuefu Zhuyutang， 7.02 g·kg^-1） group， a co-treatment （Didang Xianxiong decoction， 8.10 g·kg^-1） group， an alagebrium chloride （3 mg·kg^-1） group， and a model group. Except for normal group， the other rats was induced by a single intraperitoneal injection of 55 mg·kg^-1streptozotocin （STZ） to establish DM model. After adaptive feeding for three weeks， the rats were treated correspondingly by gavage daily for eight weeks. Rats were sampled under anesthesia. Enzyme-linked immunosorbent assay（ELISA） was used to detect the protein expression of TLR4 and tumor necrosis factor-alpha （TNF-<italic>α</italic>） in myocardial tissues. The expression levels of NF-<italic>κ</italic>B p65 and I<italic>κ</italic>B<italic>α</italic> were detected by immunohistochemistry. NF-<italic>κ</italic>B p65， I<italic>κ</italic>B<italic>α</italic>， TNF-<italic>α</italic>， and TLR4 mRNA expression levels were detected by real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR）. Result:The protein and mRNA levels of TLR4， NF-<italic>κ</italic>B p65， I<italic>κ</italic>B<italic>α</italic>， and TNF-<italic>α </italic>were higher in the model group than those in the normal group （<italic>P</italic><0.01）. TLR4， NF-<italic>κ</italic>B p65， I<italic>κ</italic>B<italic>α</italic>， and TNF-<italic>α</italic> protein and mRNA expression levels were reduced to varying degrees in the groups with drug intervention as compared with those in the model group （<italic>P</italic><0.01）. The inter-group comparison revealed that the co-treatment group showed more manifest reduction in protein and mRNA expression levels of TLR4， NF-<italic>κ</italic>B p65， I<italic>κ</italic>B<italic>α，</italic> and TNF-<italic>α </italic>than the phlegm-resolving group and the stasis-resolving group （<italic>P</italic><0.05<italic>，P</italic><0.01）. Conclusion:The co-treatment of phlegm and stasis can improve myocardial inflammation in DM rats， with superior effect to either the phlegm-resolving method or the stasis-resolving method. The underlying mechanism may be related to the inhibition of TLR4/NF-<italic>κ</italic>B/I<italic>κ</italic>B signaling pathway activation.

Aplicabilidade do Activated Sludge Model No. 1 (ASM 1) para simulação do cotratamento de esgoto sanitário e lixiviado de aterro sanitário em lagoas aeradas / Activated Sludge Model No. 1 (ASM1) applicability for simulation of sanitary sewage and landfill leachate co-treatment in aerated lagoons

RESUMO A necessidade crescente de alternativas para o tratamento e a disposição de lixiviados de aterros sanitários é uma realidade no Brasil, principalmente com os avanços estabelecidos pela Política Nacional de Resíduos Sólidos a partir de 2010 e consequentes metas de substituição de lixões por aterros sanitários. Uma alternativa empregada, devido à facilidade de implantação, é o cotratamento com esgoto sanitário, por meio do recebimento do lixiviado em estações de tratamento de esgoto (ETE). Este estudo avaliou a aplicabilidade do Activated Sludge Model No. 1 (ASM1) para lagoas aeradas promovendo o cotratamento de esgoto e lixiviado. Os cenários simulados consistiram em proporções crescentes de adição de lixiviado ao sistema - que variaram de 0 a 10% - e, para cada um deles, foi avaliado o desenvolvimento de biomassa heterotrófica e autotrófica, o consumo de demanda química de oxigênio (DQO) em diferentes frações, a nitrificação, o consumo de oxigênio e a alcalinidade. Os resultados das simulações geradas indicaram que o modelo foi otimista em relação ao período de partida do sistema e à adaptação das comunidades microbianas consideradas frente aos cenários progressivamente agressivos oferecidos pela maior presença de lixiviado. Porém, representou adequadamente o prejuízo à qualidade do efluente devido à matéria orgânica recalcitrante e aos problemas relacionados à manutenção da nitrificação, frente ao aumento da capacidade de aeração e da demanda de alcalinidade. O ASM1 teve boa aplicabilidade, portanto, como ferramenta para avaliar qualitativamente o comportamento de ETE ao receber lixiviado para cotratamento e corroborar os riscos associados a essa alternativa, necessitando, porém, de modificações e detalhamentos adicionais para otimização de sistemas reais.

ABSTRACT The growing necessity for alternative landfill leachate treatment and disposal is a reality in Brazil, mainly when the advancements of the National Policy on Solid Wastes (2010) established goals for replacing dumping grounds with landfills. Due to its simplicity, a usual alternative is to perform co-treatment of municipal sewage and landfill leachate in wastewater treatment plants (WWTPs). This study assessed the applicability of the Activated Sludge Model No 1 (ASM1) to aerated lagoons promoting sewage and leachate co-treating. The simulated scenarios consisted of increasing proportions of leachate addition to the system, ranging from 0 to 10%, and for each of them the development of heterotrophic and autotrophic biomass, COD consumption in different fractions, nitrification, oxygen consumption and alkalinity were evaluated. The simulation results showed that the model was optimistic regarding the treatment system startup and microbial communities adaptation when exposed to increasingly aggressive conditions due to leachate addition. However, it correctly represented the detrimental effects on effluent quality due to recalcitrant organic matter and the issues with maintaining proper nitrification regarding aeration capacity and alkalinity demands. ASM1 has good applicability, therefore, as a tool to qualitatively assess the behavior of WWTP when receiving leachate for co-treatment and corroborates the risks associated with this alternative, however, requiring further modifications and details to optimize real systems.

Apoptotic Effect of Co-treatment with Curcumin and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

Curcumin is a widely used flavoring agent in food, and it has been reported to inhibit cell growth, to induce apoptosis, and to have antitumor activity in many cancers. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatment with curcumin and cisplatin on human tongue SCC25 cells. To investigate whether the co-treatment efficiently reduced the viability of the SCC25 cells compared with the two treatments separately, an MTT assay was conducted. The induction and the augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and an analysis of DNA hypoploidy. Western blot, MMP and immunofluorescence tests were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following the co-treatment. In this study, following the co-treatment with curcumin and cisplatin, the SCC25 cells showed several forms of apoptotic manifestation, such as nuclear condensation, DNA fragmentation, reduction of MMP, increased levels of Bax, decreased levels of Bcl-2, and decreased DNA content. In addition, they showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40 (CAD) to the nuclei, and activation of caspase-7, caspase-3, PARP, and DFF45 (ICAD). In contrast, separate treatments of 5 microM of curcumin or 4 microg/ml of cisplatin, for 24 hours, did not induce apoptosis. Therefore, our data suggest that combination therapy with curcumin and cisplatin could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

Tratamento combinado de lixiviado de aterros de resíduos sólidos urbanos e esgoto doméstico como alternativa para a solução de um grave problema ambiental e de saúde pública - revisão bibliográfica. / Co-treatment of municipal solid waste landfill leachate and domestic wastewater as an alternative solution to a serious environmental and public health problem - a literature review.

A disposição de lixiviados de aterros de resíduos sólidos urbanos é um grande problema de saúde ambiental, com impactos sobre a saúde das populações que vivem em áreas circunvizinhas, devido às características poluentes deste lixiviado. Uma opção é coletar e direcionar o lixiviado para estações de tratamento de esgotos, nas quais podem ser tratados conjuntamente com o esgoto doméstico. A viabilidade dessa opção depende da existência de rede coletora de esgotos próxima ao aterro e da capacidade da estação de tratamento em assimilar as cargas, sobretudo orgânica e nitrogenada, advindas do lixiviado. Este trabalho apresenta uma revisão bibliográfica sobre o tratamento combinado de lixiviado e esgoto doméstico. Os estudos realizados mostram que a quantidade limite de lixiviado a ser recebida em estações de tratamento, sem comprometer a qualidade do efluente final, não é fixa, dada a grande variabilidade da composição dos lixiviados. Entretanto, a maioria dos estudos não apresenta variações significativas de qualidade para efluentes do tratamento combinado com até 2% de volume de lixiviado.

The disposal of municipal solid waste landfill leachates is a major environmental health problem, with impacts on the health of people living in surrounding areas due to the characteristics of leachate pollutants. One option is to collect and direct the leachate to sewage treatment plants, where it can be co-treated with domestic sewage. The viability of this option depends on the existence of sewerage near the landfill and the treatment plant capacity to absorb the loads, especially organic and nitrogen, stemming from leachate. This paper presents a literature review on combined treatment of leachate and domestic sewage. Studies show that the quantity limit of leachate to be received on treatment plants, without compromising the quality of the final effluent, is not fixed, given the great variability in the composition of leachate. However, most studies present no significant variations in quality for effluent treatment combined with up to 2% of the volume of leachate.