Can Chinese herbal medicine offer feasible solutions for newly diagnosed esophageal cancer patients with malnutrition? a multi-institutional real-world study.

Background: Esophageal cancer (EC) is a major cause of cancer-related mortality in Taiwan and globally. Patients with EC are highly prone to malnutrition, which adversely affects their prognosis. While Chinese herbal medicine (CHM) is commonly used alongside conventional anti-cancer treatments, its long-term impact on EC patients with malnutrition remains unclear. Methods: This study utilized a multi-center cohort from the Chang Gung Research Database, focusing on the long-term outcomes of CHM in EC patients with malnutrition between 1 January 2001, and 31 December 2018. Patients were monitored for up to 5 years or until death. Overall survival (OS) rates were calculated using the Kaplan-Meier method. Overlap weighting and landmark analysis were employed to address confounding and immortal time biases. Additionally, the study analyzed prescription data using a CHM network to identify key CHMs for EC with malnutrition, and potential molecular pathways were investigated using the Reactome database. Results: EC patients with malnutrition who used CHM had a higher 5-year OS compared with nonusers (22.5% vs. 9% without overlap weighting; 24.3% vs. 13.3% with overlap weighting; log-rank test: p = 0.006 and 0.016, respectively). The median OS of CHM users was significantly longer than that of nonusers (19.8 vs. 12.9 months, respectively). Hazard ratio (HR) analysis showed a 31% reduction in all-cause mortality risk for CHM users compared with nonusers (HR: 0.69, 95% confidence interval: 0.50-0.94, p = 0.019). We also examined 665 prescriptions involving 306 CHM, with Hedyotis diffusa Willd. exhibiting the highest frequency of use. A CHM network was created to determine the primary CHMs and their combinations. The identified CHMs were associated with the regulation of immune and metabolic pathways, particularly in areas related to immune modulation, anti-cancer cachexia, promotion of digestion, and anti-tumor activity. Conclusion: The results of this study suggest a correlation between CHM use and improved clinical outcomes in EC patients with malnutrition. The analysis identified core CHMs and combinations of formulations that play a crucial role in immunomodulation and metabolic regulation. These findings lay the groundwork for more extensive research on the use of CHM for the management of malnutrition in patients with EC.

Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin's beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin's potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.

HemU and TonB1 contribute to hemin acquisition in Stenotrophomonas maltophilia.

Introduction: The hemin acquisition system is composed of an outer membrane TonB-dependent transporter that internalizes hemin into the periplasm, periplasmic hemin-binding proteins to shuttle hemin, an inner membrane transporter that transports hemin into the cytoplasm, and cytoplasmic heme oxygenase to release iron. Fur and HemP are two known regulators involved in the regulation of hemin acquisition. The hemin acquisition system of Stenotrophomonas maltophilia is poorly understood, with the exception of HemA as a TonB-dependent transporter for hemin uptake. Methods: Putative candidates responsible for hemin acquisition were selected via a homolog search and a whole-genome survey of S. maltophilia. Operon verification was performed by reverse transcription-polymerase chain reaction. The involvement of candidate genes in hemin acquisition was assessed using an in-frame deletion mutant construct and iron utilization assays. The transcript levels of candidate genes were determined using quantitative polymerase chain reaction. Results: Smlt3896-hemU-exbB2-exbD2-tonB2 and tonB1-exbB1-exbD1a-exbD1b operons were selected as candidates for hemin acquisition. Compared with the parental strain, hemU and tonB1 mutants displayed a defect in their ability to use hemin as the sole iron source for growth. However, hemin utilization by the Smlt3896 and tonB2 mutants was comparable to that of the parental strain. HemA expression was repressed by Fur in iron-replete conditions and derepressed in iron-depleted conditions. HemP negatively regulated hemA expression. Like hemA, hemU was repressed by Fur in iron-replete conditions; however, hemU was moderately derepressed in response to iron-depleted stress and fully derepressed when hemin was present. Unlike hemA and hemU, the TonB1-exbB1-exbD1a-exbD1b operon was constitutively expressed, regardless of the iron level or the presence of hemin, and Fur and HemP had no influence on its expression. Conclusion: HemA, HemU, and TonB1 contribute to hemin acquisition in S. maltophilia. Fur represses the expression of hemA and hemU in iron-replete conditions. HemA expression is regulated by low iron levels, and HemP acts as a negative regulator of this regulatory circuit. HemU expression is regulated by low iron and hemin levels in a hemP-dependent manner.

Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/ßKlotho/FGFs Pathways in Mice.

The farnesoid X receptor (FXR)/ßKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR agonist, GW4064, and FXR-knockout (FXR-KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight-junction markers (claudin1 and zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, ßKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR-KO mice had decreased levels. FXR-KO mice exhibited elevated colon cancer markers (ß-catenin, LGR5, CD44, CD34, and cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR-KO mice versus wild-type mice post LPS exposure emphasize the pivotal role of FXR in preserving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/ßKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

Corrigendum: Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: a real-world comparative cohort study.

[This corrects the article DOI: 10.3389/fphar.2022.978814.].

Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: A real-world comparative cohort study.

Introduction: In Taiwan, many people receive Chinese herbal medicine (CHM) as an alternative choice to help control body weight. However, the clinical effectiveness of CHM on weight control has not been well studied, while potential risks and adverse effects are still unknown. The aim of our study is to find out a safe and efficient treatment model of CHM for weight control compared to liraglutide in a real-world setting. Methods: we retrospectively analyzed obese subjects [body mass index (BMI)≧25 kg/m2] from Chang Gung Research Database (2013-2018). We evaluated the effect on body weight and BMI changes in obese groups receiving CHM or western medicine (WM, represented liraglutide) within 180 days. The proportion of subjects who achieved 5 and 10% weight reduction was calculated as well. Furthermore, the potential adverse events were analyzed during the study period. Overlap weighting was used to balance the baseline differences between CHM and WM groups. Results: The full cohort comprised 1,360 participants: 701 in the CHM group and 659 in the WM group. At baseline, the CHM group was younger (42.75 ± 12.12 years old in CHM vs. 52.31 ± 11.7 years old in WM, p-value <0.001) and has more female subjects (77.6% in CHM vs. 53.0% in WM, p-value <0.001). On the other hand, CHM users had lower body weight (79.83 ± 15.66 kg vs. 84.68 ± 17.14 kg, p-value <0.001) and BMI (30.58 ± 5.20 vs. 32.84 ± 6.95, p-value <0.001). At day 180, CHM users lost more body weight (-4.5 ± 4.07 kg vs. -2.15 ± 4.05 kg, p-value <0.001) and higher reduction in BMI (-1.77 ± 1.73 vs. -0.9 ± 2.14, p-value <0.001). A total of 53.21% (n = 373) CHM users lost at least 5% of body weight (22.46% for WM users, p-value <0.001), and 18.97% (n = 132) lost at least 10% of body weight (4.55% for WM users, p-value <0.001). The benefit remained consistent with and without overlap weighting. For adverse events, 18 cases of hypertension occurred in 659 subjects in the WM group (2.7%) in comparison to 1 of 701 subjects in the CHM group (0.1%). Conclusion: CHM led to clinically meaningful weight loss without serious adverse events in a real-world setting. Further clinical trials are warranted to validate this result.

Effects of nerve-sparing procedures on surgical margins after robot-assisted radical prostatectomy.

BACKGROUND: Nerve-sparing (NS) techniques could potentially increase positive surgical margins after robot-assisted radical prostatectomy (RARP). Nevertheless, the available studies have revealed ambiguous results among distinct groups. This study purposed to clarify the details of NS techniques to accurately estimate their influence on margin status. METHODS: We studied RARPs performed by one surgeon from 2010 to 2018. Surgical margins were evaluated by the laterality and levels of NS techniques in site-specific prostate lobes. The multivariable analysis evaluated the effects of nerve-sparing procedures, combined with other covariate factors, on margin status. RESULTS: Overall, 419 RARPs involving 838 prostate lobes were analyzed. Notably, 181 patients (43.4%) had pT2-stage, and 236 (56.6%) had pT3-stage cancer. The PSM rates for patients who underwent unilateral, bilateral, and non NS procedures were 30.3%, 28.8%, and 50%, respectively ( p = 0.233) or in stratification by pT2 ( p = 0.584) and pT3 ( p = 0.116) stage. The posterolateral PSM rates among site-specific prostate lobes were 10.9%, 22.4%, and 18.9% for complete, partial, and non NS techniques, respectively ( p = 0.001). The partial NS group revealed a significant increase in PSM rate compared with the complete NS (OR 2.187, 95% CI: 1.19-4.03) and non NS (OR 2.237, 95% CI: 1.01-4.93) groups in site-specific prostate lobes. CONCLUSION: Partial NS procedures have a potential risk of increasing the positive surgical margins rate than complete and non NS procedures do. Therefore, correct case selection is required before performing partial NS techniques.

The Potential Complementary Role of Using Chinese Herbal Medicine with Western Medicine in Treating COVID-19 Patients: Pharmacology Network Analysis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in 2019-coronavirus disease (COVID-19). More and more Western medicine (WM) and Chinese herbal medicine (CHM) treatments have been used to treat COVID-19 patients, especially among Asian populations. However, the interactions between WM and CHM have not been studied. This study aims at using the network pharmacology approach to explore the potential complementary effects among commonly used CHM and WM in a clinical setting from a biomolecular perspective. Three well-published and widely used CHM formulas (National Research Institute of Chinese Medicine 101 (NRICM101), Qing-Fei-Pai-Du-Tang (QFPDT), Hua-Shi-Bai-Du-Formula (HSBDF)) and six categories of WM (Dexamethasone, Janus kinase inhibitors (JAKi), Anti-Interleukin-6 (Anti-IL6), anticoagulants, non-vitamin K antagonist oral anticoagulants (NOAC), and Aspirin) were included in the network pharmacology analysis. The target proteins on which these CHM and WM had direct effects were acquired from the STITCH database, and the potential molecular pathways were found in the REACTOME database. The COVID-19-related target proteins were obtained from the TTD database. For the three CHM formulas, QFPDT covered the most proteins (714), and 27 of them were COVID-19-related, while HSBDF and NRICM101 covered 624 (24 COVID-19-related) and 568 (25 COVID-19-related) proteins, respectively. On the other hand, WM covered COVID-19-related proteins more precisely and seemed different from CHM. The network pharmacology showed CHM formulas affected several inflammation-related proteins for COVID-19, including IL-10, TNF-α, IL-6, TLR3, and IL-8, in which Dexamethasone and Aspirin covered only IL-10 and TNF-α. JAK and IL-6 receptors were only inhibited by WM. The molecular pathways covered by CHM and WM also seemed mutually exclusive. WM had advantages in cytokine signaling, while CHM had an add-on effect on innate and adaptive immunity, including neutrophil regulation. WM and CHM could be used together to strengthen the anti-inflammation effects for COVID-19 from different pathways, and the combination of WM and CHM may achieve more promising results. These findings warrant further clinical studies about CHM and WM use for COVID-19 and other diseases.

Reinforcing a Thermoplastic Starch/Poly(butylene adipate-co-terephthalate) Composite Foam with Polyethylene Glycol under Supercritical Carbon Dioxide.

Biodegradable foams are a potential substitute for most fossil-fuel-derived polymer foams currently used in the cushion furniture-making industry. Thermoplastic starch (TPS) and poly(butylene adipate-co-terephthalate) (PBAT) are biodegradable polymers, although their poor compatibility does not support the foam-forming process. In this study, we investigated the effect of polyethylene glycol (PEG) with or without silane A (SA) on the foam density, cell structure and tensile properties of TPS/PBAT blends. The challenges in foam forming were explored through various temperature and pressure values under supercritical carbon dioxide (CO2) conditions. The obtained experimental results indicate that PEG and SA act as a plasticizer and compatibilizer, respectively. The 50% (TPS with SA + PEG)/50% PBAT blends generally produce foams that have a lower foam density and better cell structure than those of 50% (TPS with PEG)/50% PBAT blends. The tensile property of each 50% (TPS with SA + PEG)/50% PBAT foam is generally better than that of each 50% (TPS with PEG)/50% PBAT foam.

Prediction of a positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy.

The positive surgical margin (PSM) and biochemical recurrence (BCR) are two main factors associated with poor oncotherapeutic outcomes after prostatectomy. This is an Asian population study based on a single-surgeon experience to deeply investigate the predictors for PSM and BCR. We retrospectively included 419 robot-assisted radical prostatectomy cases. The number of PSM cases was 126 (30.1%), stratified as 22 (12.2%) in stage T2 and 103 (43.6%) in stage T3. Preoperative prostate-specific antigen (PSA) > 10 ng/mL (p = 0.047; odds ratio [OR] 1.712), intraoperative blood loss > 200 mL (p = 0.006; OR 4.01), and postoperative pT3 stage (p < 0.001; OR 6.901) were three independent predictors for PSM while PSA > 10 ng/mL (p < 0.015; hazard ratio [HR] 1.8), pT3 stage (p = 0.012; HR 2.264), International Society of Urological Pathology (ISUP) grade > 3 (p = 0.02; HR 1.964), and PSM (p = 0.027; HR 1.725) were four significant predictors for BCR in multivariable analysis. PSMs occurred mostly in the posterolateral regions (73.8%) which were associated with nerve-sparing procedures (p = 0.012) while apical PSMs were correlated intraoperative bleeding (p < 0.001). A high ratio of pT3 stage after RARP in our Asian population-based might surpass the influence of PSM on BCR. PSM was less significant than PSA and ISUP grade for predicting PSA recurrence in pT3 disease. Among PSM cases, unifocal and multifocal positive margins had a similar ratio of the BCR rate (p = 0.172) but ISUP grade > 3 (p = 0.002; HR 2.689) was a significant BCR predictor. These results indicate that PSA and pathological status are key factors influencing PSM and BCR.

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most crucial causes of chronic kidney disease (CKD). However, the efficacy and biomedical mechanisms of Chinese herbal medicine (CHM) for DKD in clinical settings remain unclear. OBJECTIVE: This study aimed to analyze the outcomes of DKD patients with CHM-only management and the possible molecular pathways of CHM by integrating web-based biomedical databases and real-world clinical data. METHODS: A total of 152,357 patients with incident DKD from 2004 to 2012 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. The risk of mortality was estimated with the Kaplan-Meier method and Cox regression considering demographic covariates. The inverse probability of treatment weighting was used for confounding bias between CHM users and nonusers. Furthermore, to decipher the CHM used for DKD, we analyzed all CHM prescriptions using the Chinese Herbal Medicine Network (CMN), which combined association rule mining and social network analysis for all CHM prescriptions. Further, web-based biomedical databases, including STITCH, STRING, BindingDB, TCMSP, TCM@Taiwan, and DisGeNET, were integrated with the CMN and commonly used Western medicine (WM) to explore the differences in possible target proteins and molecular pathways between CHM and WM. An application programming interface was used to assess these online databases to obtain the latest biomedical information. RESULTS: About 13.7% (20,947/131,410) of patients were classified as CHM users among eligible DKD patients. The median follow-up duration of all patients was 2.49 years. The cumulative mortality rate in the CHM cohort was significantly lower than that in the WM cohort (28% vs 48%, P<.001). The risk of mortality was 0.41 in the CHM cohort with covariate adjustment (99% CI 0.38-0.43; P<.001). A total of 173,525 CHM prescriptions were used to construct the CMN with 11 CHM clusters. CHM covered more DKD-related proteins and pathways than WM; nevertheless, WM aimed at managing DKD more specifically. From the overrepresentation tests carried out by the online website Reactome, the molecular pathways covered by the CHM clusters in the CMN and WM seemed distinctive but complementary. Complementary effects were also found among DKD patients with concurrent WM and CHM use. The risk of mortality for CHM users under renin-angiotensin-aldosterone system (RAAS) inhibition therapy was lower than that for CHM nonusers among DKD patients with hypertension (adjusted hazard ratio [aHR] 0.47, 99% CI 0.45-0.51; P<.001), chronic heart failure (aHR 0.43, 99% CI 0.37-0.51; P<.001), and ischemic heart disease (aHR 0.46, 99% CI 0.41-0.51; P<.001). CONCLUSIONS: CHM users among DKD patients seemed to have a lower risk of mortality, which may benefit from potentially synergistic renoprotection effects. The framework of integrating real-world clinical databases and web-based biomedical databases could help in exploring the roles of treatments for diseases.

Associations Between Using Chinese Herbal Medicine and Long-Term Outcome Among Pre-dialysis Diabetic Nephropathy Patients: A Retrospective Population-Based Cohort Study.

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear. Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan's National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis. Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value <0.001), and the risk of mortality was 0.42 (95% CI: 0.36-0.49; p-value <0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55-0.63; p-value <0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.), Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf., Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs. Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials.

Decreased drug resistance of bladder cancer using phytochemicals treatment.

The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24-GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24-GCB cells in a dose-dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24-GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24-GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24-GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Identifying the Chinese Herbal Medicine Network and Core Formula for Allergic Rhinitis on a Real-World Database.

MATERIALS AND METHODS: Patients with a primary diagnosis of AR (ICD-9-CM code: 477.9) in 2010 were included, and the National Health Insurance Research Database in Taiwan was used as the data source. Association rule mining and social network analysis were used to establish and explore the CHM network. Possible molecular pathways of the CHM network were summarized and compared with commonly used western medicine (WM) by conducting overrepresentation analysis in the Reactome pathway database. The potential proteins acted by CHMs were obtained from the CHM ingredient-protein databases, including STITCH, TCMSP, TCMID, and TCM@Taiwan. RESULTS: There were 89,148 AR subjects found in 2010, and a total of 33,507 patients ever used CHM. On an average, 5.6 types of CHMs were utilized per prescription. Xin-Yi-Qing-Fei-Tang was used most frequently (25.5% of 222,279 prescriptions), while Xiao-Qing-Long-Tang with Xin-Yi-San was the most commonly prescribed CHM-CHM combination. Up to six distinctive clusters could be found among the CHM network, and core CHMs could be found for AR, such as Xiao-Qing-Long-Tang and Xin-Yi-Qing-Fei-Tang. A total of 140 molecular pathways were covered by the CHM network (2,432 ingredients from 31 kinds of CHMs), while 39 WMs covered 55 pathways. Among pathways responding to the immune system, WM mainly acted on cytokine signaling-related pathways, while CHM mostly acted on neutrophil/macrophage-related innate pathways and dendritic cell-related adaptive immunity pathways. CONCLUSION: Our study demonstrated and analyzed the CHM network for AR. Core CHM for AR and possible molecular pathways were presented as well, and this information is crucial for researchers to select candidates for CHM-related studies.

The modulation study of multiple drug resistance in bladder cancer by curcumin and resveratrol.

Gemcitabine (GCB), which functions via the inhibition of DNA synthesis, is commonly used in the treatment of bladder cancer; however, its response rate is not satisfactory due to the development of drug resistance. The potential for phytochemicals to reverse drug resistance in bladder cancer tumor cells was evaluated. A human bladder cancer cell line, T24, was cultured, and GCB-resistant cells (T24-GCB) were also established. The acquired resistance of T24-GCB to GCB was measured using an MTT assay. The gene expression of ATP-binding cassette (ABC) transporter protein family members was analyzed using reverse transcription-quantitative PCR analysis, and western blotting was performed to verify ABC family protein, cytoplasmic thymidine kinase (TK) and poly (ADP-ribose) polymerase (PARP) expression on whole cell lysates. Subsequently, resveratrol and curcumin were used to evaluate their modulation potential in decreasing the drug resistance of T24-GCB cells to GCB using MTT and migration assays. T24-GCB cells have increased drug resistance ability, with an 18.75-fold higher ID50 value compared with native T24 cells (105 vs. 5.6 nM). T24-GCB cells also exhibit increased cross resistance to mitomycin C and paclitaxel. The mRNA expression of ABCC2 in T24-GCB cells increased compared with that in native T24 cells. Via western blot analysis, it was determined that the expression of ABCC2 protein was also increased in T24-GCB cells. Conversely, the expression of ABCB1, ABCG2, deoxycytidine kinase (DCK), TK1 and TK2 decreased. Following curcumin and resveratrol treatment alone or combined with GCB, additive cytotoxic enhancement was observed, and the migratory abilities of T24-GCB cells were significantly decreased. Western blot analysis revealed that ABCC2 protein expression increased, and DCK, TK1 and TK2 expression decreased following co-treatment of T24-GCB cells with GCB + curcumin or resveratrol compared with GCB alone. Of note, there was a marked increase in cleaved-PARP expression in T24-GCB cells treated with a combination of GCB + curcumin or resveratrol. Both curcumin and resveratrol could reverse the drug resistance of T24-GCB cells in an additive pattern though PARP enhancement without changes in ABCC2 and DCK, TK1 and TK2 expression.

An Investigation of the Prescription Patterns of Chinese Herbal Products for Chronic Glomerulonephritis Patients: A Hospital-Based Cross-Sectional Study.

Chronic kidney disease (CKD) has a high incidence and prevalence worldwide, and chronic glomerulonephritis (CGN) is one of the main causes of CKD. Therefore, it is important to diagnose and treat CGN early. The purpose of this study is to analyze the prescription patterns and frequencies of Chinese herbal products (CHPs) for CGN by using a hospital-based database from the Chang Gung Memorial Hospital (CGMH), a large, tertiary hospital system in Taiwan, and to evaluate the safety and possible efficacy of CHPs by blood test. The International Classification of Disease Ninth Revision (ICD-9) code 582 was used to identify patients with CGN. From 2004 to 2015, a total of 54726 CHP prescriptions for CGN were provided. Association rule mining was used to analyze the prevalent of CHP combination patterns in treating CGN. Jia-Wei-Xiao-Yao-San (JWXYS) and Gorgon (Euryale feroxSalisb.) were the most frequently prescribed herbal formula (HF) and single herb (SH), respectively. The most frequently prescribed combination of CHPs was that of JWXYS with Bu-Yang-Huan-Wu-Tang (BYHWT) in CGMH. In statistical, the level of eGFR in Stage 3a and 3b group was increasing after treatment in 6 and 12 months and might not cause the renal function to worsen within 12-month treatments. To the best of our knowledge, this is the first pharmacoepidemiological study to review CHP treatments for CGN. However, additional studies and clinical trials are needed to provide data on the safety and efficacy of these CHPs.

Efficacy of Traditional Chinese Medicine in Xerostomia and Quality of Life during Radiotherapy for Head and Neck Cancer: A Prospective Pilot Study.

Xerostomia is one of the most common acute and late complications of radiotherapy for head and neck cancer, and it affects quality of life. We conducted a prospective study to evaluate the efficacy of traditional Chinese medicine (TCM) in toxicities and quality of life during radiotherapy. Head and neck cancer patients who were scheduled for radiotherapy were checked for inclusion/exclusion criteria before enrollment. Patients in the study group (inpatients) were hospitalized in a Chinese medicine ward and received concomitant TCM intervention during radiotherapy, while those in the control group (outpatients) received only conventional cancer treatments at the Western outpatient department. The primary end point was amelioration of postradiotherapy side effects. The secondary end points were quality of life during the cancer therapy and occurrence of adverse events following the TCM treatments. Thirty inpatients and 50 outpatients completed the study. Compared to the control group, those in the TCM group had decreased severity of xerostomia. There was no treatment-related impairment of renal or hepatic function among TCM group. Although better outcomes of social contact, dyspnea, physical and emotional function, and financial problems were found in the TCM group, we need further confirmation about the impact of hospitalization itself on these results.

Are there useful CT features to differentiate renal cell carcinoma from lipid-poor renal angiomyolipoma?

OBJECTIVE: This study was an attempt to identify key CT features that can potentially be used to differentiate between lipid-poor renal angiomyolipoma and renal cell carcinoma (RCC). MATERIALS AND METHODS: We conducted an analysis of patients who received nephrectomy or renal biopsy from 2002 to 2011 with suspected RCC. We included tumors smaller than 7 cm with a completed three-phase CT examination. A radiologist and a urology fellow, blinded to histopathologic diagnosis, recorded the imaging findings by consensus and compared the values for each parameter between lipid-poor angiomyolipoma, RCC subtypes, and RCC as a group. Multivariate logistic regression analysis was performed for each univariate significant feature. RESULTS: The sample in our study consisted of 132 patients with 135 renal tumors, including 51 men (age range, 26-84 years; mean age, 57 years) and 81 women (age range, 29-91 years; mean age, 57 years). These tumors included 33 lipid-poor angiomyolipomas, 54 clear-cell RCC, 31 chromophobe RCC, and 17 papillary RCC. Multivariate analysis revealed four significant parameters for differentiating RCC as a group from lipid-poor angiomyolipoma (angular interface, p = 0.023; hypodense rim, p = 0.045; homogeneity, p = 0.005; unenhanced attenuation > 38.5 HU, p < 0.001), five for clear-cell RCC, two for chromophobe RCC, and one for papillary RCC. Lipid-poor angiomyolipoma and clear-cell RCC showed early strong enhancement and a washout pattern, whereas chromophobe RCC and papillary RCC showed gradual enhancement over time. CONCLUSION: Specific CT features can potentially be used to differentiate lipid-poor renal angiomyolipoma from renal cell carcinoma.