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Background: Mitochondrial dysfunction is considered to be an important contributor in podocyte injury under diabetic conditions. The BaoShenTongLuo (BSTL) formula has been shown to reduce podocyte damage and postpone the progression of diabetic kidney disease (DKD). The potential mechanisms underlying the effects of BSTL, however, have yet to be elucidated. In this study, we aimed to investigate whether the effects of BSTL are related to the regulation of mitochondrial biogenesis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. Methods: High-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer (HPLC–ESI–MS) analysis was performed to investigate the characteristics of pure compounds in BSTL. db/db mice and mouse podocyte clone-5 (MPC5) cells were exposed to high glucose (HG) to induce DKD and podocyte damage. Body weight, random blood glucose, urinary albumin/creatinine ratio (UACR), indicators of renal function and renal histological lesions were measured. Markers of podocyte injury, mitochondrial morphology, mitochondrial deoxyribonucleic acid (mtDNA) content, mitochondrial respiratory chain complexes activities, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) levels were assessed. Protein expressions of AMPK, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), transcription factor A (TFAM), mitochondrial fusion protein 2 (MFN2) and dynamin-related protein 1 (DRP1) were also detected. MPC5 cells were transfected with AMPKα small interfering RNA (AMPKα siRNA) to determine the underlying mechanisms of BSTL improvement of mitochondrial function under diabetic conditions. Results: In vivo, treatment with BSTL reduced the UACR levels, reversed the histopathological changes in renal tissues, and alleviated the podocyte injury observed in db/db mice. After BSTL treatment, the decreased mtDNA content and mitochondrial respiratory chain complex I, III, and IV activities were significantly improved, and these effects were accompanied by maintenance of the protein expression of p-AMPKαT172, PGC-1α, TFAM and MFN2. The in vitro experiments also showed that BSTL reduced podocyte apoptosis, suppressed excessive cellular ROS production, and reversed the decreased in MMP that were observed under HG conditions. More importantly, the effects of BSTL in enhancing mitochondrial biogenesis and reducing podocyte apoptosis were inhibited in AMPKα siRNA-treated podocytes. Conclusion: BSTL plays a crucial role in protecting against podocyte injury by regulating the AMPK-mediated mitochondrial biogenesis in DKD. [ABSTRACT FROM AUTHOR]

Objective: Endoscopy is the main method to treat gastrointestinal neuroendocrine tumors (GI-NETs), but the specific indications are still controversial. We aim to investigate the clinical outcomes of GI-NETs patients who experienced endoscopic submucosal dissection (ESD). Methods: We retrospectively reviewed the clinical features and prognosis of 65 GI-NETs patients who underwent ESD between 2008 and 2018. Results: A total of 65 patients diagnosed with GI-NETs pathologically, bearing 75 lesions, were found by endoscopy incidentally for other symptoms. The locations of these lesions were stomach (n = 24), duodenal bulb (n = 4) and rectum (n = 47). The diameter of 75 tumors were as follows: size ≤ 1 cm (78.7%), 1 cm < size ≤ 2 cm (17.3%), 2 cm < size ≤ 3.5 cm (4.0%). Endoscopic ultrasonography (EUS) suggested that 72 lesions were confined to submucosa and 3 lesions invaded into muscularis propria. The rates of en bloc resection and complete resection were all 100% and the rates of intraoperative bleeding and perforation were 2.7% and 1.3%, respectively. None of the 65 patients had lymph nodes and distant metastasis during the period of study. Conclusion: For GI-NETs without lymph nodes and distant metastases, the lesion confined to submucosa with the diameter ≤1 cm is absolute indication of ESD. For rectal neuroendocrine tumors limited in submucosa with the diameter between 1 and 2 cm, and Type 1 gastric neuroendocrine tumors predicted to be T2, ESD should be prioritized to preserve gastrointestinal volume and function at initial treatment. [ABSTRACT FROM AUTHOR]

Black carbon (BC) exposure in China continues to be relatively high, prompting researchers to assess BC exposure levels using data from monitoring sites, satellite remote sensing, and models. However, data regarding the application of a combined strategy comprising the analysis of monitoring data and various types of data to simulate BC exposure levels are lacking. Hence, the current study seeks to estimate short- and long-term BC exposure levels by combining national monitoring data with data from the second Modern-Era Retrospective analysis for Research and Applications (MERRA-2). Furthermore, this study attempts to improve the spatio-temporal resolution of BC exposure levels using Bayesian maximum entropy (BME). The BME model performed well in terms of estimating short- (R2 = 0.74 and RMSE = 1.76 μg/m3) and long-term (R2 = 0.76 and RMSE = 1.3 μg/m3) exposure. Premature mortalities and economic losses were also assessed by applying localised concentration–response coefficients simulated in China. A total of 74,500 (95% confidence interval (CI): 23,900–124,500) and 538,400 (95% CI: 495,000–581,300) all-cause premature mortality cases were found to be associated with short- and long-term BC exposure, respectively. Meanwhile, short-term BC exposure was associated with economic losses ranging from 7.5 to 13.2 billion US dollars (USD) (1 USD = 6.36 RMB on January 19, 2022) based on amended human capital (AHC) and willingness to pay (WTP), accounting for 0.06%–0.1% of China's total gross domestic product (GDP) in 2017 (1.2 × 104 billion USD), respectively. The economic losses for long-term exposure varied from 53 to 93.2 billion USD based on AHC and WTP, accounting for 0.4%–0.8% of China's total GDP in 2017, respectively. [Display omitted] • Modelled black carbon (BC) exposure level was the highest in Sichuan Basin, China. • All-cause premature mortalities due to long-term BC exposure were 538,400 cases in 2017. • Economic losses due to BC exposure accounted for 0.8% of the 2017 GDP of China. [ABSTRACT FROM AUTHOR]

Planetary boundaries have received considerable attention since they were first proposed, but applying various downscaling methods to the regional scale has certain limitations due to regional heterogeneity. The concept of ecological boundaries (EB) extends and complements planetary boundaries at a regional scale. However, previous studies have not considered the EB of multiple regions and the impact of interregional ecosystem service value (ESV) flows on EB. In this study, we optimized the EB accounting method and quantified the EB of 30 provinces in China from 2002 to 2017, then assessed the ecosystem unsustainability, and determined the impact of demand for goods and services on the consumption of local natural resources by each province in China using an ESV-extended multiregional input-output model. We found that EB increased in all provinces of China. The ecological unsustainability index of all 30 provinces was larger than 1, indicating a serious environmental unsustainability, but the magnitude of the index tends to decrease. Furthermore, the regions that have the greatest impact on exceeding EB in each province were concentrated in Guangdong and Henan. Guangdong had the highest total net imports in 2012 and 2015 (665.08 and 641.70 billion yuan, respectively), while Henan had the highest total net imports in 2017 (611.58 billion yuan). For the role of net exports, the rankings of the provinces differed in terms of the direct ESV and the boundary-exceeding ESV indicators. Our results reveal EB across provinces in China, underscoring the importance of considering the flow of ESV between regions in assessing the impact of exceeding EB. This study can assist policymakers in better allocating ecological resources within EB, which is critical for alleviating ecological pressures. [ABSTRACT FROM AUTHOR]

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions-Severity of Illness scale (CGI-SI) and Clinical Global Impressions-Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96-11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed at identifying new ABO alleles from155 unrelated blood samples with potential ABO discrepancy in a Chinese Han population of 835 144 donors., Background: Serological strategies and genotyping are crucial for the precise determination of ABO discrepancy., Methods: Their ABO phenotypes and plasma glycosyltransferase activity were determined by standard forward and reverse typing and dilution tests. The genomic DNA of the ABO gene was amplified by polymerase chain reaction and sequenced. The frequency of ABO subgroup alleles associated with ABO discrepancy was analysed., Results: Serological analysis indicated that 53, 96 and 6 samples with ABO discrepancy were identified in the A, B and O subgroups, respectively. Genetic analysis revealed 12 novel alleles among the 46 associated with serologic ABO discrepancy. The majority of novel alleles was obtained from point mutations or single base insertion in Exons 6 to 7 of the ABO gene. The most frequent alleles were ABO*cisAB.01 (14/53, 26.42%) and ABO*A2.05 (7/53, 13.2%) in the A subgroup and ABO*BA.02 (34/96, 35.42%) and ABO*BEL.11 (15/96, 15.62%) in the B subgroup. Samples with the same ABO subgroup allele displayed different phenotypes, such as ABO*AX.13, ABO*BW.03, ABO*BW.12, ABO*BW.15, ABO*BEL.03, ABO*BEL.10 and ABO*BEL.11., Conclusion: This study identified 12 novel alleles among the 46 associated with serologic ABO discrepancies. ABO genotyping is needed for the accurate evaluation of blood phenotype to improve the safety of blood transfusion., (© 2020 British Blood Transfusion Society.)

Objectives: To evaluate the safety and efficacy of endoscopic resection and discuss the treatment strategy of small gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. Material and methods: The data of 713 patients, who underwent endoscopic submucosal dissection (ESD) for gastric submucosal tumors (SMTs), were retrospectively analyzed. We investigated the clinicopathological features and analyzed the risk potential of small gastric GISTs, and documented therapeutic and follow-up outcomes. We also compared the follow-up results between operated patients and 58 patients who were suspected of small gastric GISTs and underwent regular surveillance under endoscopic ultrasound (EUS) in the same period. Results: GISTs were the most common gastric SMTs (289 cases, 40.5%), of which small GISTs were found in 250 cases. The mitotic index was less than 5 in all cases. However, 122 out of 250 cases (48.8%) had adverse factors under EUS, which were related to tumor size ( p  < .01). ESD was successfully performed in all patients, and no serious complication or perioperative death occurred. The follow-up period for 42.07 ± 22.49 months revealed improvement of symptoms in 80.2% patients and showed no recurrence or metastasis. Of the 58 patients selected for EUS surveillance, 48 (82.8%) presented with gastrointestinal symptoms and 41 out of 48 (85.4%) were not relieved during follow-up and 16 (27.6%) with severe psychological problems. Conclusions: ESD is a safe and effective treatment for small GISTs, which helps to confirm the diagnosis, improve symptoms and reduce the psychological pressure. Thus, we recommend endoscopic resection is a good option for small gastric GISTs once diagnosed.