High-resolution maps show that rubber causes substantial deforestation.

Understanding the effects of cash crop expansion on natural forest is of fundamental importance. However, for most crops there are no remotely sensed global maps1, and global deforestation impacts are estimated using models and extrapolations. Natural rubber is an example of a principal commodity for which deforestation impacts have been highly uncertain, with estimates differing more than fivefold1-4. Here we harnessed Earth observation satellite data and cloud computing5 to produce high-resolution maps of rubber (10 m pixel size) and associated deforestation (30 m pixel size) for Southeast Asia. Our maps indicate that rubber-related forest loss has been substantially underestimated in policy, by the public and in recent reports6-8. Our direct remotely sensed observations show that deforestation for rubber is at least twofold to threefold higher than suggested by figures now widely used for setting policy4. With more than 4 million hectares of forest loss for rubber since 1993 (at least 2 million hectares since 2000) and more than 1 million hectares of rubber plantations established in Key Biodiversity Areas, the effects of rubber on biodiversity and ecosystem services in Southeast Asia could be extensive. Thus, rubber deserves more attention in domestic policy, within trade agreements and in incoming due-diligence legislation.

Changes in Induced-Antipredation Defense Traits and Transcriptome Regulations of Daphnia magna in Response to 5-HT1A Receptor Antagonist.

The serotonin signaling system plays a crucial role in regulating the ontogeny of crustaceans. Here, we describe the effects of different concentrations of the 5-hydroxytryptamine 1A receptor antagonist (WAY-100635) on the induced antipredation (Rhodeus ocellatus as the predator), morphological, behavioral, and life-history defenses of Daphnia magna and use transcriptomics to analyze the underlying molecular mechanisms. Our results indicate that exposure to WAY-100635 leads to changes in the expression of different defensive traits in D. magna when faced with fish predation risks. Specifically, as the length of exposure to WAY-100635 increases, high concentrations of WAY-100635 inhibit defensive responses associated with morphological and reproductive activities but promote the immediate negative phototactic behavioral defense of D. magna. This change is related to the underlying mechanism through which WAY-100635 interferes with gene expression of G-protein-coupled GABA receptors by affecting GABBR1 but promotes serotonin receptor signaling and ecdysteroid signaling pathways. In addition, we also find for the first time that fish kairomone can significantly activate the HIF-1α signaling pathway, which may lead to an increase in the rate of immediate movement. These results can help assess the potential impacts of serotonin-disrupting psychotropic drugs on zooplankton in aquatic ecosystems.

The appearance and increase in the quantity and proportion of the clinical research coordinator's service fee in drug clinical trial research fund and its impact on trial quality.

OBJECTIVE: The changes of absolute value and relative value of clinical research coordinator service fee and its influence on the quality of drug clinical trial were analyzed. METHODS: This study compared the amount and structural changes of drug clinical trial costs in before 3 years and after 3 years of self-examination and inspection initiated by the China Food and Drug Administration, identified the increase number and composition of each individual cost of a clinical trial research funds which including clinical research coordinator service fee, investigator labor fee, subjects examination fee, subjects traffic subsidy, documents management fee, drug management fee, etc. RESULT: The most significant appearance of increase in volume and proportion was the clinical research coordinator service fee. From the initial few to the global multicenter tumor drug clinical trials RMB31,624 or 34.92% of the proportion and domestic multicenter tumor drug clinical trials RMB16,500, accounted for 33.74%. DISCUSSION: It has become common for more money to be spent on clinical trials to be accompanied by improved quality, but the occurrence and continuous increase of clinical research coordinator service fee were divided into two aspects, On the one hand, the quality of clinical trials was promoted by the large amount of low-skill trivial work undertaken by clinical research coordinator; on the other hand, the quality of clinical trials was undermined by the fact that clinical research coordinator did too much treatment evaluation work that should have been done by the investigator. CONCLUSION: The clinical research coordinators' access standards, pre-employment training and examination, job and performance evaluation, in addition to the SMO specification management and avoiding malicious competition between the industry, are important factors in the quality assurance of drug clinical trials.

Getting Road Expansion on the Right Track: A Framework for Smart Infrastructure Planning in the Mekong.

The current unprecedented expansion of infrastructure promises to enhance human wellbeing but risks causing substantial harm to natural ecosystems and the benefits they provide for people. A framework for systematically and proactively identifying the likely benefits and costs of such developments is badly needed. Here, we develop and test at the subregional scale a recently proposed global scheme for comparing the potential gains from new roads for food production with their likely impact on biodiversity and ecosystem services. Working in the Greater Mekong-an exceptionally biodiverse subregion undergoing rapid development-we combined maps of isolation from urban centres, yield gaps, and the current area under 17 crops to estimate where and how far road development could in principle help to increase food production without the need for cropland expansion. We overlaid this information with maps summarising the importance of remaining habitats to terrestrial vertebrates and (as examples of major ecosystem services) to global and local climate regulation. This intersection revealed several largely converted yet relatively low-yielding areas (such as central, eastern, and northeastern Thailand and the Ayeyarwady Delta), where narrowing yield gaps by improving transport links has the potential to substantially increase food production at relatively limited environmental cost. Concentrating new roads and road improvements here while taking strong measures to prevent their spread into areas which are still extensively forested (such as northern Laos, western Yunnan, and southwestern Cambodia) could thus enhance rural livelihoods and regional food production while helping safeguard vital ecosystem services and globally significant biological diversity.

Correlations and stratification analysis between premature ejaculation and psychological disorders.

We studied the associations and correlations between premature ejaculation (PE) and psychological disorders, such as anxiety and depression, in new perspectives with an aim of improving PE patients' treatment outcomes. Between December 2017 and December 2018, we selected 1,010 men aged over 18 years old. Self-estimated IELT, the premature ejaculation diagnostic tool, the International Index of Erectile Function-5, the General Anxiety Disorder-7 and the Patients Health Questionnaire-9 were used to measure latency time, premature ejaculation, erectile dysfunction, anxiety and depression respectively. Premature ejaculation patients were categorised into two types: lifelong PE (LPE) and acquired PE (APE). Among the 958 men evaluated, the prevalence of anxiety and depression in PE group was 82.07% (444/541) and 74.68% (404/541) respectively. Premature ejaculation patients after adjustment for age, negative association of IIEF-5 and positive relation of PEDT score with GAD-7/PHQ-9 were observed (p < 0.01 for all). These associations in men with LPE were stronger than APE. Stratification of the duration of PE showed that the longer the duration is, the more the prevalence of anxiety and depression will be. Age stratification showed that under the impact of PE, young men tend to have severe psychological problems.

China's fight to halt tree cover loss.

China is investing immense resources for planting trees, totalling more than US$ 100 billion in the past decade alone. Every year, China reports more afforestation than the rest of the world combined. Here, we show that China's forest cover gains are highly definition-dependent. If the definition of 'forest' follows FAO criteria (including immature and temporarily unstocked areas), China has gained 434 000 km2 between 2000 and 2010. However, remotely detectable gains of vegetation that non-specialists would view as forest (tree cover higher than 5 m and minimum 50% crown cover) are an order of magnitude less (33 000 km2). Using high-resolution maps and environmental modelling, we estimate that approximately 50% of the world's forest with minimum 50% crown cover has been lost in the past approximately 10 000 years. China historically lost 1.9-2.7 million km2 (59-67%), and substantial losses continue. At the same time, most of China's afforestation investment targets environments that our model classes as unsuitable for trees. Here, gains detectable via satellite imagery are limited. Conversely, the regions where modest gains are detected are environmentally suitable but have received little afforestation investment due to conflicting land-use demands for agriculture and urbanization. This highlights the need for refined forest monitoring, and greater consideration of environmental suitability in afforestation programmes.

Hypoxia-induced regulation of placental REDD1 and mTOR was impaired in a rat model of estrogen-induced cholestasis.

PURPOSE: Hypoxia inducible factor-1α (HIF-1α), regulated in development and DNA damage response-1 (REDD1), and mammalian target of rapamycin (mTOR) play distinct roles in response to hypoxia. The aim of this study was to evaluate whether the HIF-1α-REDD1-mTOR-mediated hypoxic stress response also operates normally in estrogen-induced cholestasis. METHODS: Pregnant rats were administered with ethinylestradiol (EE) to induce cholestasis and then were subjected to feto-placental ischemia reperfusion (IR); as controls, one group received neither EE nor IR, and another two groups received only EE or IR. RESULTS: Giving rats either EE alone or IR alone increased placental levels of HIF-1α, REDD1, glucose transporter-1 (GLUT1), and phosphoglycerate kinase-1 (PGK1), and decreased placental mTOR and lactic dehydrogenase A (LDHA) expression compared with the control rats. Subjecting EE-treated rats to IR did not further alter placental levels of REDD1 or mTOR, while it did elevate placental HIF-1α, GLUT1, and PGK1 expression, and decline LDHA expression. By contrast, mRNA levels did not differ significantly among the four groups for any of the proteins analyzed. CONCLUSIONS: This study manifested that placental HIF-1α and its downstream glucose metabolism effectors can effectively react to hypoxia in EE-induced cholestasis rats. However, hypoxia-induced REDD1 and mTOR alternation, which responds efficiently in normal placentas, was impaired in EE-induced cholestasis placentas.

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.

BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.

To Evaluate the Value of Vertebral Body Cortical Thickness in Predicting Osteoporosis by Opportunistic CT.

BACKGROUND: In vertebrae, the amount of cortical bone has been estimated at 30-60%, but 45-75% of axial load on a vertebral body is borne by cortical bone (1). RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of vertebral body cortical thickness in predicting osteoporosis (OP) by analyzing the relationship between vertebral body cortical thickness and bone mineral density (BMD) in different age and gender groups. The optimal diagnostic cut-off value of vertebral body cortical thickness in predicting OP was analyzed. MATERIALS AND METHODS: The data of 150 patients (50-89 years old) who underwent chest or abdominal Quantitative computed tomography (QCT) scan (obtained in one scan) in our hospital from July 2021 to July 2022 were retrospectively analyzed. The average volume bone mineral density (vBMD) of L1-L2 vertebral bodies was obtained and grouped according to BMD, age, and gender. According to BMD, the patients were divided into three groups: osteoporosis, osteopenia and normal. According to age, the patients were divided into three groups: 50-59 years, 60-69 years and ≥70 years. The axial images of T11, T12 and L1 were reconstructed with 1.25 mm slice thickness by AW4.7 workstation provided by General Electric Co (GE) Company. The images were imported into the computed tomography (CT) Spine Bone Quantification System software for spine analysis, and the vertebral body cortical thickness values were obtained. CT Spine Bone Quantification System is a software for quantitative analysis and separation of cortical bone and cancellous bone. RESULTS: A total of 150 patients were enrolled in this study, including 49 patients in the osteoporosis group, 51 patients in the osteopenia group, and 50 patients in the normal group. The cortical thickness values of T11, T12 and L1 were positively correlated with BMD, and the correlation coefficient was 0.750 at T11. According to the receiver operating characteristic (ROC) curve analysis of T11, T12, L1 cortical thickness value and BMD, OP was diagnosed when T11 < 2.75 mm, T12 < 3.06 mm, and L1 < 2.67 mm. The sensitivity was 83.67%, 87.76%, 75.51%, respectively. The specificity was 79.21%, 71.29% and 90.10%, respectively, and the difference was statistically significant. CONCLUSION: Vertebral body cortical thickness is correlated with BMD and age. According to the cut-off value of different vertebral bodies, OP can be predicted when T11 < 2.75 mm or T12 < 3.06 mm or L1 < 2.67 mm.

Gamma-Aminobutyric Acid Enhances Cadmium Phytoextraction by Coreopsis grandiflora by Remodeling the Rhizospheric Environment.

Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant-soil systems remain unknown. In this study, different GABA dosages (0-8 g kg-1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9-159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant-soil systems.

A Multicenter, Randomized, Controlled Study of the Breast Biopsy and Circumferential Excision System for Breast Lesions.

BACKGROUND: This study aimed to verify the effectiveness, safety, and reliability of the breast biopsy and circumferential excision system. METHODS: It was designed as a multicenter, randomized, open-label, positive control, noninferiority trial. A total of 168 subjects who met the breast lesion screening requirements of the clinical trial protocol were randomly divided into a breast biopsy and circumferential excision dual cutting system test group or Mammotome control group. The main outcome was the successful removal rate of suspected lumps during surgery. Secondary outcomes included the operative times for individual lumps, weight of removed cord tissue, and several indicators of device performance. Safety indicators, including routine blood, blood biochemical and electrocardiogram examinations, were measured at baseline and 24 hours and 48 hours after the operation. Postoperative complications and combined medication use were observed and recorded until 7 days after the operation. RESULTS: The results showed no significant differences in efficacy and safety between the 2 groups (main efficacy, P = .7463; all secondary efficacy indicators, P > .05, except weight of removed cord tissue [P = .0070] and touch sensitivity of the device interface [P = .0275]; all safety indicators, P > .05). The results suggested that the test device is effective and is acceptable safe for use in breast lesion biopsy. CONCLUSION: For patients with a high incidence of breast lesions, the results of this study provide a safe, effective, sensitive and accessible option for the removal of breast mass biopsies at a price much lower than that of imported devices.

Efficacy and safety of Chinese herbal medicine children's Zibei Xuanfei syrup in treating acute trachea-bronchitis with wind-heat invading lung syndrome: A randomized, double-blind, multicentre, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx. AIM OF THE STUDY: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome. MATERIALS AND METHODS: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit. RESULTS: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug. CONCLUSION: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children.

Pharmacokinetics, Bioequivalence, and Safety Studies of Amlodipine Besylate in Healthy Subjects.

This study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, single-dose, crossover, dual-period study and was divided into fasting and postprandial human bioequivalence trials. In the first trial after overnight fasting, 28 subjects were given 5-mg amlodipine besylate tablets via oral administration, and blood specimens were obtained up to 144 hours after dosing; another 28 subjects had a high-fat meal 1 hour before drug administration and proceeded the same as the fasting trial. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, log AUC from time 0 to infinity, and log peak concentration. The plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. The safety was assessed throughout the study. The results show that no significant differences were observed between the pharmacokinetic profiles of the test and reference amlodipine besylate tablets in the fasting and postprandial trials. The 90%CIs of the peak concentration, AUC from time 0 to the last quantifiable concentration and AUC from time 0 to infinity of amlodipine in the 2 trials were within the commonly accepted bioequivalence criteria of 80% to 125%. Compared with the pharmacokinetic parameters of the fasting and postprandial trials, food had no significant effect on exposure of amlodipine besylate. There was no significant difference in safety statistical results between the 2 groups. The results suggest that generic and original amlodipine besylate tablets are bioequivalent with similar safety profiles.

Rhizospheric microbiomics integrated with plant transcriptomics provides insight into the Cd response mechanisms of the newly identified Cd accumulator Dahlia pinnata.

Phytoremediation that depends on excellent plant resources and effective enhancing measures is important for remediating heavy metal-contaminated soils. This study investigated the cadmium (Cd) tolerance and accumulation characteristics of Dahlia pinnata Cav. to evaluate its Cd phytoremediation potential. Testing in soils spiked with 5-45 mg kg-1 Cd showed that D. pinnata has a strong Cd tolerance capacity and appreciable shoot Cd bioconcentration factors (0.80-1.32) and translocation factors (0.81-1.59), indicating that D. pinnata can be defined as a Cd accumulator. In the rhizosphere, Cd stress (45 mg kg-1 Cd) did not change the soil physicochemical properties but influenced the bacterial community composition compared to control conditions. Notably, the increased abundance of the bacterial phylum Patescibacteria and the dominance of several Cd-tolerant plant growth-promoting rhizobacteria (e.g., Sphingomonas, Gemmatimonas, Bryobacter, Flavisolibacter, Nocardioides, and Bradyrhizobium) likely facilitated Cd tolerance and accumulation in D. pinnata. Comparative transcriptomic analysis showed that Cd significantly induced (P < 0.001) the expression of genes involved in lignin synthesis in D. pinnata roots and leaves, which are likely to fix Cd2+ to the cell wall and inhibit Cd entry into the cytoplasm. Moreover, Cd induced a sophisticated signal transduction network that initiated detoxification processes in roots as well as ethylene synthesis from methionine metabolism to regulate Cd responses in leaves. This study suggests that D. pinnata can be potentially used for phytoextraction and improves our understanding of Cd-response mechanisms in plants from rhizospheric and molecular perspectives.

Circular RNAs and Their Role in Exosomes.

As a novel class of endogenous non-coding RNAs discovered in recent years, circular RNAs (circRNAs) are highly conserved and stable covalently closed ring structures with no 5'-end cap or 3'-end poly(A) tail. CircRNAs are formed by reverse splicing, mainly by means of a noose structure or intron complementary pairing. Exosomes are tiny discoid vesicles with a diameter of 40-100 nm that are secreted by cells under physiological and pathological conditions. Exosomes play an important role in cell-cell communication by carrying DNA, microRNAs, mRNAs, proteins and circRNAs. In this review, we summarize the biological functions of circRNAs and exosomes, and further reveal the potential roles of exosomal circRNAs in different diseases, providing a scientific basis for the diagnosis, treatment, and prognosis of a wide variety of diseases.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Polyaspartic acid enhances the Cd phytoextraction efficiency of Bidens pilosa by remolding the rhizospheric environment and reprogramming plant metabolism.

The green soil chelator polyaspartic acid (PASP) can enhance heavy metal phytoextraction efficiency, but the potential mechanisms are not clearly understood from the whole soil-plant system. In this study, we explored the effects and potential mechanisms of PASP addition in soils on plant growth and cadmium (Cd) uptake in the Cd hyperaccumulator Bidens pilosa by analysing variations in chemical elements, rhizospheric microbial community, and plant metabolomics. The results showed that PASP significantly promoted the biomass yield and Cd concentration in B. pilosa, leading to an increase in the total accumulated Cd by 46.4% and 76.4% in shoots and 124.7% and 197.3% in roots under 3 and 6 mg kg-1 PASP addition, respectively. The improved soil-available nutrients and enriched plant growth-promoting rhizobacteria (e.g., Sphingopyxis, Sphingomonas, Cupriavidus, Achromobacter, Nocardioides, and Rhizobium) were probably responsible for the enhanced plant growth after PASP addition. The increase in Cd uptake by plants could be due to the improved rhizosphere-available Cd, which was directly activated by PASP and affected by the induced rhizobacteria involved in immobilizing/mobilizing Cd (e.g., Sphingomonas, Cupriavidus, Achromobacter, and Rhizobium). Notably, PASP and/or these potassium (K)-solubilizing rhizobacteria (i.e., Sphingomonas, Cupriavidus, and Rhizobium) highly activated rhizosphere-available K to enhance plant growth and Cd uptake in B. pilosa. Plant physiological and metabolomic results indicated that multiple processes involving antioxidant enzymes, amino acids, organic acids, and lipids contributed to Cd detoxification in B. pilosa. This study provides novel insights into understanding how soil chelators drive heavy metal transfer in soil-plant systems.

The impact of COVID-19 on the clinical trial.

The objective of this study was to explore the impact of the coronavirus disease 2019 epidemic on ongoing and upcoming drug clinical trials. Qualitative semi-structured interviews were conducted with clinical trial staff and clinical trial subjects were surveyed by questionnaire in this study. The results of interviews and questionnaire showed that coronavirus disease 2019 pandemic has led to many changes in the implementation of drug clinical trials, including: a variety of meetings being held online webinars using various platforms, telemedicine and follow-up by video, A large number of deviations from protocol and losses of follow-up, delivery of clinical trial drugs by express, additional workload caused by screening for coronavirus, and anxiety of subjects. These results suggest that the coronavirus disease 2019 outbreak has hindered the progress and damaged the quality of clinical trials. The online meeting, remote follow-up, express delivery of drugs and remote monitoring in the epidemic environment can ensure the progress of clinical trials to a certain extent, but they cannot fully guarantee the quality as before.

Pharmacokinetics, Bioequivalence, and Safety Studies of Pantoprazole Sodium Enteric-Coated Tablets in Healthy Subjects.

This study aimed to evaluate the bioequivalence of 2 pantoprazole sodium enteric-coated tablet formulations, a generic formulation and a branded formulation, and to investigate their pharmacokinetic and safety profiles. The study was designed as a single-center, randomized, open-label, single-dose, dual-period, and 2-sequence crossover trial, and was divided into fasting and postprandial human bioequivalence trials. In the first trial, 36 subjects were fasted overnight before they were given generic or branded tablets (during 2 separate administration periods). Separately, 42 subjects were provided a high-fat meal 1 hour before the drugs were administered. Blood specimens of each subject were obtained up to 24 hours after drug administration. No significant differences were observed between the pharmacokinetic profiles of the generic and branded pantoprazole sodium enteric-coated tablets. Bioequivalence was evaluated using 90% confidence intervals for the ratio of test/reference log area under the concentration-time curve over 24 hours, log area under the concentration-time curve to infinity (AUC0-∞ ), and log peak concentration (Cmax ). The 90% confidence intervals of the least squares geometric mean ratio of Cmax , area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t ), and AUC0-∞ of 36 subjects in the fasting trial and of 40 of 41 subjects in the postprandial trial (Cmax [41], AUC0-t [41], and AUC0-∞ [40]) were in accordance with the bioequivalence criteria. No severe adverse effects were detected. The generic and branded pantoprazole sodium enteric-coated tablets were considered bioequivalent with similar safety profiles.

Bioinformatics Analysis: The Regulatory Network of hsa_circ_0007843 and hsa_circ_0007331 in Colon Cancer.

OBJECTIVE: To analyze the molecular regulation network of circular RNA (circRNA) in colon cancer (CC) by bioinformatics method. METHODS: hsa_circ_0007843 and hsa_circ_0007331 proved to be associated with CC in previous studies were chosen as the research object. ConSite database was used to predict the transcription factors associated with circRNA, and the CC-associated transcription factors were screened out after intersection. The CircInteractome database was used to predict the RNA-binding proteins (RBPs) interacting with circRNAs and screen out the CC-associated RBPs after an intersection. Furthermore, the CircInteractome database was used to predict the miRNAs interrelated with circRNAs, and the HMDD v3.2 database was used to search for miRNAs associated with CC. The target mRNAs of miRNA were predicted by the miRWalk v3.0 database. CC-associated target genes were screened out from the GeneCards database, and the upregulated genes were enriched and analyzed by the FunRich 3.1.3 software. Finally, the molecular regulatory network diagram of circRNA in CC was plotted. RESULTS: The ConSite database predicted a total of 14 common transcription factors of hsa_circ_0007843 and hsa_circ_0007331, among which Snail, SOX17, HNF3, C-FOS, and RORα-1 were related to CC. The CircInteractome database predicted that the RBPs interacting with these two circRNAs were AGO2 and EIF4A3, and both of them were related to CC. A total of 17 miRNAs interacting with hsa_circ_0007843 and hsa_circ_0007331 were predicted by CircInteractome database. miR-145-5p, miR-21, miR-330-5p, miR-326, and miR-766 were associated with CC according to the HMDDv3.2 database. miR-145-5p and miR-330-5p, lowly expressed in CC, were analyzed in the follow-up study. A total of 676 common target genes of these two miRNAs were predicted by the miRWalk3.0 database. And 57 target genes were involved in the occurrence and development of CC from the GeneCards database, with 23 genes downregulated and 34 genes upregulated. Additionally, GO analysis showed that the 34 upregulated genes were mainly enriched in biological processes such as signal transduction and cell communication. KEGG pathway analysis showed that the upregulated genes were closely related to integrin, ErbB receptor, and ALK1 signal pathways. Finally, a complete regulatory network of hsa_circ_0007843 and hsa_circ_0007331 in CC was proposed, whereby each one of the participants was either directly or indirectly associated and whose deregulation may result in CC progression. CONCLUSION: Predicting the molecular regulatory network of circRNAs by bioinformatics provides a new theoretical basis for further occurrence and development pathogenesis of CC and good guidance for future experimental research.