Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer.

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.

The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv/Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc/ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc. Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

Charged Fibrous Dressing to Promote Diabetic Chronic Wound Healing.

Diabetic chronic wounds cause a significant amount of pain to patients because of their low cure rates and high recurrence rates. Traditional approaches to treating diabetic chronic wounds often involve the delivery of drugs or cytokines that regulate the microenvironment and eliminate bacterial infection in the wound area, but they are passive in controlling cell behaviors and may lead to drug resistance. Emerging drug-free wound treatments are important for convenient, effective, and safe treatment strategies. However, the current approaches cannot fully promote tissue regeneration or prevent bacterial infections. Here, the efficacy of a negatively charged fiber dressing in promoting diabetic chronic wound healing is investigated. The negatively charged fiber dressing can generate reactive oxygen species to inhibit bacterial reproduction with the assistance of ultrasound during the inflammatory phase. Furthermore, the dressing provides an electrostatic field that regulates cellular behavior during the inflammatory and proliferative phases. In particular, the dressing can promote fibroblast migration and induce macrophage polarization and neovascularization without any additional drugs. It is demonstrated that this strategy enables the healing of diabetic chronic wounds in a mouse model, achieving effective wound closure over a 12-day treatment cycle and providing a drug-free therapeutic strategy for diabetic chronic wound care.

Native forests transformed into cash crops reduced soil multi-functionality by modifying the microbial community composition and keystone species' abundance in the Jianghuai Hilly Region.

Conversion of native forest to cash crops is the predominant form of land use change in the Jianghuai Hilly Region. However, how plantations with different cash crops affect the soil multi-functionality is not well documented. In this study, we collected three kinds of cash crops soils (vegetable, orchard, and tea) and forest soil, to systematically review the relationship between soil microbial communities and soil multi-functionality. Soil multi-functionality had decreased in vegetable and orchard as compared to native forest, whereas tea plantation had no significant effects on soil multi-functionality. The results also showed that cash crop plantations decreased soil multi-functionality by shifting keystone species' abundance, for forest, vegetable, and orchard, the keystone species that were classified as module hubs in the bacterial co-occurrence network significantly negatively contributed to soil multi-functionality, but the keystone species categorized as module hubs in fungal co-occurrence network positively affected soil multi-functionality. Multiple soil properties were the drivers of the soil microbial community; thus, indicating that the altered soil properties under cash crop plantations were vital in determining microbial composition and biological processes. These results identified that sustainable management strategy in cash crop plantation needed to be developed for improving soil multi-functionality.

Ni(I)-Catalyzed Hydroxylation of Aryl Halides with Water under Thermal Catalysis.

A highly efficient hydroxylation of (hetero)aryl halides using water as a hydroxyl source via Ni catalysis promoted by PhSiH3 under thermal catalysis is reported. This methodology provides a general procedure to obtain diverse multifunctional pharmaceutically phenols and polyphenols, some of which are proven challenging to be synthesized using literature methods. Mechanism studies demonstrated that the addition of PhSiH3 led to the generation of active Ni(I) species, which catalyze the hydroxylation via a Ni(I)-Ni(III) pathway.

Linking clinotypes to phenotypes and genotypes from laboratory test results in comprehensive physical exams.

BACKGROUND: In this work, we aimed to demonstrate how to utilize the lab test results and other clinical information to support precision medicine research and clinical decisions on complex diseases, with the support of electronic medical record facilities. We defined "clinotypes" as clinical information that could be observed and measured objectively using biomedical instruments. From well-known 'omic' problem definitions, we defined problems using clinotype information, including stratifying patients-identifying interested sub cohorts for future studies, mining significant associations between clinotypes and specific phenotypes-diseases, and discovering potential linkages between clinotype and genomic information. We solved these problems by integrating public omic databases and applying advanced machine learning and visual analytic techniques on two-year health exam records from a large population of healthy southern Chinese individuals (size n = 91,354). When developing the solution, we carefully addressed the missing information, imbalance and non-uniformed data annotation issues. RESULTS: We organized the techniques and solutions to address the problems and issues above into CPA framework (Clinotype Prediction and Association-finding). At the data preprocessing step, we handled the missing value issue with predicted accuracy of 0.760. We curated 12,635 clinotype-gene associations. We found 147 Associations between 147 chronic diseases-phenotype and clinotypes, which improved the disease predictive performance to AUC (average) of 0.967. We mined 182 significant clinotype-clinotype associations among 69 clinotypes. CONCLUSIONS: Our results showed strong potential connectivity between the omics information and the clinical lab test information. The results further emphasized the needs to utilize and integrate the clinical information, especially the lab test results, in future PheWas and omic studies. Furthermore, it showed that the clinotype information could initiate an alternative research direction and serve as an independent field of data to support the well-known 'phenome' and 'genome' researches.

MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesenchymal stem cells.

INTRODUCTION: Mesenchymal stem cells (MSCs) play an important role in the pathology of preeclampsia (PE). The survival of MSCs and angiogenesis in the maternal-fetal interface are important for a successful pregnancy. MicroRNA-136 (miR-136) is highly expressed in decidua-derived MSCs (MSCs) from PE compared with healthy donors (NC). The role of the MSCs aberrant expressed miR-136 in PE development is still unclear. In the present study, we examined the impact of miR-136 on the survival of MSCs and angiogenesis in the maternal-fetal interface. METHODS: MSCs were extracted and transfected with miR-136 mimic and interfering RNAs using lipofectamine-2000. Then cell apoptosis were tested using flow cytometry. HUVEC tube formation ability was tested on Matrigel co-cultured with conditioned MSCs supernatants. RESULTS: High level of miR-136 could suppress cell proliferation and promote apoptosis of MSCs through targeting BCL2. It could also impairs HUVEC capillary formation by suppressing VEGF. DISCUSSION: MiR-136 significantly increase the apoptosis and suppress the proliferation of MSCs. It could also inhibit the capillary formation and trophoblast cell invasion. These data suggest that decidua-derived miR-136 that is increased in PE is a potential causal factor of PE.

Survival benefit of traditional chinese herbal medicine (a herbal formula for invigorating spleen) in gastric cancer patients with peritoneal metastasis.

Objective. We evaluated the efficiency of traditional Chinese herbal medicine (a compound herbal formula for invigorating spleen) as a complementary and alternative therapy for gastric cancer patients with peritoneal metastasis. Methods. Between 2001 and 2012, 93 gastric cancer patients with peritoneal metastasis were enrolled in this study. The effect of traditional Chinese herbal medicine on their long-term outcome was investigated. Kaplan-Meier method was used to assess the difference in survival time, and Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Result. First-line palliative chemotherapy plus traditional Chinese herbal medicine was performed in 47 patients and the other 46 patients received chemotherapy alone. The overall survival was different between patients with and without traditional Chinese herbal medicine (12.0 versus 10.5 months; P = 0.046). According to the Cox proportional hazard model, first-line chemotherapy cycle (hazards ratio [HR] = 0.527; 95% CI = 0.323~0.860) and TCHM (hazards ratio [HR] = 0.644; 95% CI = 0.481~0.992) were selected as independent prognostic factors for survival. Conclusion. The results suggest that traditional Chinese herbal medicine could improve the prognosis of the gastric cancer patients with peritoneal metastasis.

The N-terminal extension of ßB1-crystallin chaperones ß-crystallin folding and cooperates with αA-crystallin.

ß/γ-Crystallins are the major structural proteins in mammalian lens. The N-terminal truncation of ßB1-crystallin has been associated with the regulation of ß-crystallin size distributions in human lens. Herein we studied the roles of ßB1 N-terminal extension in protein structure and folding by constructing five N-terminal truncated forms. The truncations did not affect the secondary and tertiary structures of the main body as well as stability against denaturation. Truncations with more than 28 residues off the N-terminus promoted the dissociation of the dimeric ßB1 into monomers in diluted solutions. Interestingly, the N-terminal extension facilitated ßB1 to adopt the correct folding pathway, while truncated proteins were prone to undergo the misfolding/aggregation pathway during kinetic refolding. The N-terminal extension of ßB1 acted as an intramolecular chaperone (IMC) to regulate the kinetic partitioning between folding and misfolding. The IMC function of the N-terminal extension was also critical to the correct refolding of ß-crystallin heteromer and the action of the lens-specific molecular chaperone αA-crystallin. The cooperation between IMC and molecular chaperones produced a much stronger chaperoning effect than if they acted separately. To our knowledge, this is the first report showing the cooperation between IMC and molecular chaperones.

Survival benefit of traditional Chinese herbal medicine (a herbal formula for invigorating spleen) for patients with advanced gastric cancer.

BACKGROUND: Traditional Chinese herbal medicine (TCHM) is widely used for advanced gastric cancer (AGC) in China. In this study, the authors analyzed the prognostic factors of selected patients with AGC, and further studied the efficacy of TCHM (a herbal formula for invigorating spleen, formerly named Wei Chang' An) on AGC. METHODS: Patients with uncured AGC were prospectively enrolled. All patients were enrolled to either the TCHM group or non-TCHM group. TCHM was administered orally to the patients in the TCHM group for 3 months or more. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors. Kaplan-Meier curves were used to assess the differences in survival time. RESULTS: There were a total of 399 eligible patients with histologically confirmed adenocarcinoma of the stomach from 2001 to 2009. In the overall group, Cox regression analysis suggested that histological type (P = .016), radiotherapy (P = .000), cycle of chemotherapy (P = .000), and TCHM (P = .000) were independent prognostic factors. In a stratification analysis of stage for 213 patients who received 3 or more cycles of chemotherapy, there was a significant increase in median overall survival from 14.0 (non-TCHM group) to 20.0 (TCHM group) months (hazard ratio [HR] = 0.538, 95% confidence interval [CI] 0.385-0.750, P = .000). Among 186 patients who did not receive chemotherapy, but best supportive care, there was a significant increase in median overall survival from 7.0 (non-TCHM group) to 14.8 (TCHM group) months (HR = 0.443, 95% CI = 0.299-0.657, P = .000). CONCLUSIONS: TCHM has an important potential value for improving the prognosis of patients with AGC.

A novel mutation in CRYBB1 associated with congenital cataract-microcornea syndrome: the p.Ser129Arg mutation destabilizes the ßB1/ßA3-crystallin heteromer but not the ßB1-crystallin homomer.

Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [θ]=0.0), which closely flanks the â-crystallin gene cluster locus. Direct sequencing of the candidate âB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant ß-crystallins revealed that the mutation impaired the structures of both ßB1-crystallin homomer and ßB1/ßA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of ßB1/ßA3-crystallin but not ßB1-crystallin. These findings highlight the importance of protein-protein interactions among ß-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC.

[Survival time of advanced gastric cancer patients treated with integrated traditional Chinese and Western medicine therapy].

BACKGROUND: Advanced gastric cancer has a low survival rate while traditional Chinese medicine (TCM) therapy has effects in inhibiting tumor growth, lengthening survival time and improving the quality of life. OBJECTIVE: To analyze the effects of integrated traditional Chinese and Western medicine therapy on the survival time and quality of life of advanced gastric cancer patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 95 advanced gastric cancer patients were enrolled and divided into comprehensive group (48 cases) and control group (47 cases). The patients in the comprehensive group from the First Department of Oncology, Longhua Hospital, were treated with TCM therapy and chemotherapy based on the gastric cancer treatment guidelines made by the First Department of Oncology of Longhua Hospital, and the patients in the control group from Renji Hospital and Ruijin Hospital in Shanghai were treated with chemotherapy only. MAIN OUTCOME MEASURES: The survival time in the two groups were observed and compared. The Karnofsky score, body weight, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) score, response rate and chemotherapy-related adverse events in the comprehensive group were observed. RESULTS: The estimated median survival time in the comprehensive group was 16.12 months, longer than 9.64 months in the control group (P<0.05). The scores of function and symptom of EORTC QLQ-C30 in the comprehensive group decreased, while the overall health status increased, and the results indicated that the quality of life of the patients in the comprehensive group was improved. In the comprehensive group, the body weight after treatment was higher than that before treatment (P=0.037), while there was no difference in Karnofsky scores between that before and after treatment (P=0.061). All the patients in the comprehensive group were assessable. The complete response rate was 0, 3 cases had a partial response, 34 cases had stable disease, and 11 cases had disease progression. The overall response rate was 6.25% (3/48), and the disease control rate was 77.08% (37/48). No patient withdrew because of severe adverse events and there was no chemotherapy-related death. CONCLUSION: Integrated traditional Chinese and Western medicine can prolong the survival time and improve the quality of life of advanced gastric cancer patients, and enhance the comprehensive effects.