Objective indexes for comparing platelet usage among peer hospitals during the COVID-19 pandemic: A cross-sectional study.

Background and Aims: Besides hospital size, clinical diagnosis and severity of patient cases determine the total platelet usage. Therefore, the appropriateness of platelet usage could not be compared simply with the total units of platelet usage in each hospital. This study aimed to objectively monitor and analyze platelet usage after implementing a single-unit issuing policy for each platelet transfusion in our hospital in October 2020. Materials and Methods: We used three objective indices, X, Y, and Z, to monitor platelet usage and compared it with other hospitals. Three indices were generated by dividing the annual total units of platelet usage by the total annual reimbursement, total number of admissions, and average total reimbursement per admission for each hospital. Results: The new indices X and Y alleviated hospital size-dependent differences. Index Y was preferred over X because its value fluctuated less during the COVID-19 pandemic. The Z index was adjusted for the average total reimbursement per admission, and the results showed that more patients with higher disease complexity did not have increased platelet usage during the COVID-19 pandemic. In our hospital (H1), index Z decreased from 2019 to 2021 due to a policy of issuing a single unit for each platelet transfusion. Conclusion: These three objective indices are suitable for peer comparison and monitoring platelet usage in hospitals, irrespective of their size. They could be applied to promote patient blood management and provide an early response to the gradual shortage of blood resources owing to the aging population and declining birth rate in Taiwan.

Rodent disturbance reduces ecosystem stability through regulating plant and soil functions in Hulun Buir steppe.

Brandt's vole (Lasiopodomys brandtii), a typical rodent in the eastern Eurasian Steppe, has unclear impacts on ecosystem stability. In our field study in the Hulun Buir steppe, a multifunctional grazing ecosystem in this region, we used burrow entrance area and burrow density as alternative disturbance indices to derive a Disturbance Index (DI) for quantifying disturbance levels from rodents, and employed generalized linear mixed-effects model and the N-dimensional hypervolume framework to assess the influence of Brandt's vole disturbance on plant and soil functions, and then on the ecosystem functional stability. Our findings unequivocally illustrate that various plant functions including vegetation cover (Cover), aboveground biomass (ABG) and shoot carbon (ShootC) significantly declined with increasing disturbance, while shoot nitrogen (ShootN) and root nitrogen (RootN) show significantly positive responses. Soil functions such as soil nitrogen (SoilN), soil phosphorus (SoilP) and soil organic carbon (SoilC) showed significantly negative responses. Notably, the burrow entrance area exerts a more pronounced impact on both plant and soil functions in comparison to burrow density. Additionally, both disturbance indicators have a more significant influence on plant functions than on soil functions. Overall, the ecosystem functional stability progressively decreases with intensified disturbance, with varying response patterns for plant and soil functions, the former exhibited heightened stability as disturbance intensified, while the latter proved more stable at moderate disturbance levels. Our findings suggest that plant functions were more susceptible to disturbance by Brandt's vole compared to soils. Additionally, an ecosystem destabilization was synchronized with increasing Brandt's vole disturbance, although alterations in the functional stability of plants and soil show a different pattern.

Predicted changes in distribution and grazing value of Stipa-based plant communities across the Eurasian steppe.

The Eurasian steppe is one of the world's largest continuous areas of grassland and has an important role in supporting livestock grazing, the most ubiquitous land use on Earth. However, the Eurasian steppe is under threat, from irrational grazing utilization, climate change, and resource exploitation. We used an ensemble modeling approach to predict the current and future distribution of Stipa-dominated plant communities in three important steppe subregions; the Tibetan Alpine, Central Asian, and Black Sea-Kazakhstan subregions. We combined this with an assessment of the grazing value of 22 Stipa species, the dominant grassland species in the area, to predict how grazing value might change under future climate change predictions. We found that the effects of changing climates on grazing values differed across the three subregions. Grazing values increased in the Tibetan alpine steppe and to a lesser extent in Central Asia, but there were few changes in the Black Sea-Kazakhstan subregion. The response of different species to changing climates varied with environmental variables. Finally, our trait-based assessment of Stipa species revealed variations in grazing value, and this had major effects on the overall grazing value of the region. Our results reinforce the importance of trait-based characteristics of steppe plant species, how these traits affect grazing value, and how grazing values will change across different areas of the Eurasian steppe. Our work provides valuable insights into how different species will respond to changing climates and grazing, with important implications for sustainable management of different areas of the vast Eurasian steppe ecosystem.

Overexpression of malic enzyme is involved in breast cancer growth and is correlated with poor prognosis.

Malic enzyme (ME) genes are key functional metabolic enzymes playing a crucial role in carcinogenesis. However, the detailed effects of ME gene expression on breast cancer progression remain unclear. Here, our results revealed ME1 expression was significantly upregulated in breast cancer, especially in patients with oestrogen receptor/progesterone receptor-negative and human epidermal growth factor receptor 2-positive breast cancer. Furthermore, upregulation of ME1 was significantly associated with more advanced pathological stages (p < 0.001), pT stage (p < 0.001) and tumour grade (p < 0.001). Kaplan-Meier analysis revealed ME1 upregulation was associated with poor disease-specific survival (DSS: p = 0.002) and disease-free survival (DFS: p = 0.003). Multivariate Cox regression analysis revealed ME1 upregulation was significantly correlated with poor DSS (adjusted hazard ratio [AHR] = 1.65; 95% CI: 1.08-2.52; p = 0.021) and DFS (AHR, 1.57; 95% CI: 1.03-2.41; p = 0.038). Stratification analysis indicated ME1 upregulation was significantly associated with poor DSS (p = 0.039) and DFS (p = 0.038) in patients with non-triple-negative breast cancer (TNBC). However, ME1 expression did not affect the DSS of patients with TNBC. Biological function analysis revealed ME1 knockdown could significantly suppress the growth of breast cancer cells and influence its migration ability. Furthermore, the infiltration of immune cells was significantly reduced when they were co-cultured with breast cancer cells with ME1 knockdown. In summary, ME1 plays an oncogenic role in the growth of breast cancer; it may serve as a potential biomarker of progression and constitute a therapeutic target in patients with breast cancer.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor-α positive ovarian cancer: The antibody-drug conjugate, payload and metabolite.

AIMS: Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate recently approved for the treatment of folate receptor-α positive ovarian cancer. The aim of this study was to develop a population pharmacokinetic model to describe the concentration-time profiles of mirvetuximab soravtansine, the payload (DM4) and a metabolite (S-methyl-DM4). METHODS: Mirvetuximab soravtansine was administered intravenously from 0.15 to 7 mg/kg to 543 patients with predominantly platinum-resistant ovarian cancer in 3 clinical studies, and the plasma drug concentrations were analysed using a nonlinear mixed-effects modelling approach. Stepwise covariate modelling was performed to identify covariates. RESULTS: We developed a semi-mechanistic population pharmacokinetic model that included linear and nonlinear routes for the elimination of mirvetuximab soravtansine and a target compartment for the formation and disposition of the payload and metabolite in tumour cells. The clearance and volume of the central compartment were 0.0153 L/h and 2.63 L for mirvetuximab soravtansine, 8.83 L/h and 3.67 L for DM4, and 2.04 L/h and 6.3 L for S-methyl-DM4, respectively. Body weight, serum albumin and age were identified as statistically significant covariates. Exposures in patients with renal or hepatic impairment and who used concomitant cytochrome P450 (CYP) 3A4 inhibitors were estimated. CONCLUSION: There is no need for dose adjustment due to covariate effects for mirvetuximab soravtansine administered at the recommended dose of 6 mg/kg based on adjusted ideal body weight. Dose adjustment is not required for patients with mild or moderate renal impairment, mild hepatic impairment, or when concomitant weak and moderate CYP3A4 inhibitors are used.

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Digitally designed occlusion of an implant-supported crown considering physiological tooth displacement under occlusal loading.

Physiological natural tooth displacement under occlusal loading can influence intraoral occlusal contacts. However, gypsum casts and digital scans cannot simulate the physiological tooth displacement under occlusal loading. The occlusal design of the implant-supported crowns has been based mainly on the experience of dental laboratory technicians, lacking accuracy and individualization. Therefore, a digital technique that considers physiological tooth displacement is presented to design the occlusion of implant-supported single crowns.

The effect of secukinumab treatment for psoriasis on serum cytokines and correlation with disease severity.

OBJECTIVE: To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients' serum METHODS: Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-1ß and IL-1RA associated with intrinsic immunity; IL-6, IL-18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL-12, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ associated with Th1; IL-23, IL-17A, and IL-22 associated with Th17; Thymus activation regulated chemokine (TARC), IL-13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)-A and IL-10 associated with angiogenesis; and IFN-γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL-23, IL-17A, IL-22 associated with Th17; TARC, IL-13, DEFB2 associated with Th2; VEGF-A, IL-10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severityï¼»Psoriasis Area Severity Index(PASI) scoreï¼½, age, and disease duration were analyzed. RESULTS: The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL-6; IL-18, GROα, IFN-γ, TNF-α, VEGF-A, and IL-17A were significantly higher than normal. And IL-17A and IFN-γ were positively correlated with disease duration and age, and IL-18 was positively correlated with PASI score. The expression levels of IL-6, GROα, VEGF-A, IFN-γ, TNF-α, IL-17A and IL-23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN-γ, VEGF-A, TARC, IL-13, and DEFB2 were still significantly higher than those of normal subjects after treatment CONCLUSIONS: secukinumab clears skin lesions by antagonizing IL-17A and simultaneously decreasing the expression levels of IL-6, GRO α, VEGF-A, IFN-γ, TNF-α, IL-17A, and IL-23.

Assessment of physiological posterior-tooth displacement under habitual occlusal force by intraoral scanning using implant-supported crowns as the reference.

STATEMENT OF PROBLEM: Studies that have used digital methods to quantitatively evaluate physiological tooth displacement under occlusal force are sparse. PURPOSE: The purpose of this clinical study was to measure physiological posterior tooth displacement under occlusal force by intraoral scanning and reverse engineering technology by using implants as the reference. MATERIAL AND METHODS: A total of 14 participants received 15 implant-supported single mandibular first molar crowns. The surface data of maxillary and mandibular posterior teeth (U1 and L1) and the buccal occlusal data in the maximum intercuspal position (MIP) with habitual occlusal force were obtained by using an intraoral scanner (TRIOS 3, v20.1.2). The U1 and L1 data were segmented into single teeth, which were then aligned to the buccal occlusal data by using the "best-fit alignment" command to build the data under occlusal force (U2 and L2). U1 and L1 data were compared with U2 and L2 data to calculate the centroid and functional cusp vertex displacements and the long axis deflections of the second premolars and second molars, taking the first molar as the reference. The medians, and first quartile (Q1), third quartile (Q3) of the above data were reported, and the Shapiro-Wilk and Wilcoxon tests were used to analyze the differences (α=.05). RESULTS: Under occlusal force, the median (Q1, Q3) centroid displacements of posterior teeth ranged from 61 (52, 101) µm to 146 (80, 186) µm; the functional cusp vertex displacements ranged from 82 (62, 117) µm to 146 (98, 189) µm, and the long axis deflections ranged from 0.45 (0.25, 0.87) degrees to 1.03 (0.52, 1.41) degrees. Mandibular second premolars displaced lingually, mesially, and apically; mandibular second molars displaced distally and apically; and maxillary second premolars and second molars displaced lingually and apically. CONCLUSIONS: A digital method taking implant-supported single crowns as the reference was used to demonstrate physiological posterior-tooth displacement under habitual occlusal force.

[Effect of acupuncture on protein kinase R-like endoplasmic reticulum kinase/eukaryotic translation initiation factor 2α signaling pathway in hippocampus of rats with post-traumatic stress disorder].

OBJECTIVE: To observe the effect of acupuncture on the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α) signaling pathway in the hippocampus of rats with post-traumatic stress disorder (PTSD), so as to explore the underlying mechanism of acupuncture in treating PTSD. METHODS: Twenty-eight SD rats were randomly divided into normal, model, acupuncture and sertraline groups, with 7 rats in each group. The PTSD model was established by single prolonged stress method. The next day after modeling, acupuncture was applied to "Baihui" (GV20) and "Dazhui" (GV14) of rats in the acupuncture group for 10 min, once a day for 7 days. Sertraline (10 mg/kg) was given by gavage to rats of the sertraline group daily for 7 days. The behavioral changes of rats were detected by elevated cross maze experiment and new object recognition experiment. The expression levels of PERK,phosphorylated(p)-PERK, eIF2α, p-eIF2α and activating transcription factor 4 (ATF4) proteins in hippocampus were detected by Western blot. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. RESULTS: Compared with the normal group, the percentage of times and retention time of entering the open arm of the elevated cross maze experiment, and new object recognition index were significantly decreased (P<0.01); the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly increased (P<0.05) of rats in the model group. Compared with the model group, the percentage of times and retention time of entering the open arm, and new object recognition index were significantly increased (P<0.05，P<0.01), the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly decreased (P<0.05, P<0.01) of rats in the acupuncture and sertraline groups; the expression level of eIF2α protein was significantly decreased (P<0.05) in the sertraline group. Hippocampal neurons in the model group were damaged, the rough endoplasmic reticulum showed severe dilation, the mitochondrial cristae showed reduction or mild cavitation; compared with the model group, hippocampal neurons structural damage and the rough endoplasmic reticulum dilation were alleviated， and only some of the mitochondrial cristae decreased in the acupuncture and sertraline groups. CONCLUSION: Acupuncture can alleviate the anxiety behavior as well as the recognition and memory ability of PTSD rats, and its mechanism may be related to the inhibition of hippocampus PERK/eIF2α signaling pathway and the reduction of hippocampal neuron damage caused by endoplasmic reticulum stress.

Phosphofructokinase Platelet Overexpression Accelerated Colorectal Cancer Cell Growth and Motility.

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC.

Effect of a novel interocclusal recording method on occlusal accuracy of implant-supported fixed prostheses: A randomized clinical trial.

OBJECTIVES: To investigate the effect of a novel interocclusal recording method on the occlusal accuracy of implant-supported fixed prostheses for partially dentate patients with distal extension. MATERIALS AND METHODS: Twenty patients with two or more adjacent teeth missing in the distal extension and scheduled to receive implant-supported fixed prostheses were enrolled. Two interocclusal recording methods were used: placing polyvinyl siloxane (PVS) on the interocclusal recording caps (test), and placing PVS on healing abutments (control). The intraoral occlusal contacts in maximal intercuspal position (MIP) were compared with those in the mounted casts to calculate sensitivity and positive predictive value (PPV). Then, patients were randomly allocated into two groups to determine which interocclusal record would be used. The implant prostheses' evaluations mainly included occlusal adjustment height, volume, and time, occlusal contact score based on articulating paper examination. Paired-samples t-test, Mann-Whitney U test, and least squares regression analyzed the statistic differences. RESULTS: The test method had higher sensitivity to detect intraoral occlusal contacts than the control method (p = .002), but similar PPV (p = .10). During the prostheses' evaluations, the occlusal adjustment height in the test group was significantly lower than that in the control group [99.4 (53.2, 134.2) vs. 159.0 (82.3, 247.8) µm, p = .03], while the occlusal contact score before adjustment was higher (p = .006). The groups had similar occlusal adjustment volume and time. CONCLUSIONS: The novel interocclusal recording method for implant-supported fixed prostheses was more accurate and could reduce the occlusal adjustment.

[Research progress on Piperis Longi Fructus and predictive analysis of its quality markers].

Piperis Longi Fructus, made from the mature and immature fruit spikes of Piper longum, is a commonly used Mongolian medicine. In recent years, researchers have gradually deepened the research on ethnic medicines and found that Piperis Longi Fructus has significant effects in adjusting blood lipids and anti-cancer. Its new chemical components and pharmacological activities are also constantly updated. Subsequently, the development and application of Piperis Longi Fructus have attracted extensive attention. Thus, it is quite urgent to establish and improve a quality evaluation system for the medicine. On the basis of summarizing the chemical components and pharmacological effects of Piperis Longi Fructus and understanding the new concept of quality marker(Q-marker), the components which can be used as its Q-markers were analyzed from the aspects of the genetic relationship, traditional medicinal effects and properties, rules of compounding and compatibility, absorbed components and testability. The research can provide reference for the establishment of a quality evaluation system for Piperis Longi Fructus.

Complete Mitochondrial Genome of Contracaecum Sp. (Nematoda: Ascarididae) from Night Herons in China.

Contracaecum species are zooparasitic anisakid nematodes and occur in gastrointestinal tracts of vertebrate/invertebrate animals, including humans, causing gastrointestinal pain, diarrhea, and increasingly severe vomiting. Although the complete mitochondrial (mt) genome (mitogenome) of Contracaecum sp. isolated from night herons in Beijing has been reported, the detailed information about this mt sequence is still puzzling. In the present study, we described the detailed characteristics across the complete mt DNA of Contracaecum sp., which includes 36 genes consisting of 12 protein genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and 2 noncoding regions (NCRs), and all genes have the same orientation of transcription. The AT content in the complete mitogenome of Contracaecum sp. was 72.2%, and it was the least value (66.7%) in the cox1 gene but was the highest rate (84.1%) in NCRs. The highest nucleotide diversity (Pi) among the genus Contracaecum was nad4 (0.190) and the least was cox1 (0.125), which indicates that nad4 might have the potential ability as useful markers to detect cryptic species in the genus Contracaecum or subspecies. Based on the maximum likelihood (ML) and Bayesian inference (BI) computational algorithms within subfamilies Ascaridoidea and Heterakoidea, the results supported that Contracaecum sp. was a new species and the family Ascaridiidae was paraphyletic. The complete mitogenome sequence of Contracaecum sp. supported a clear recognition of Contracaecum species and provided the potential existence of cryptic species in the genus Contracaecum. Our findings would better contribute to the surveillance, molecular epidemiology, and control of Contracaecum.

Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming.

Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography−mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p < 0.05) and 4 exhibited decreased levels (<0.75-fold change and p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer.

The clinical characteristic of alcohol-hyperlipidemia etiologically complex type of acute pancreatitis.

OBJECTIVE: The aim of our study was to elucidate the clinical characteristics of alcoholic-hyperlipidemic etiologically complex acute pancreatitis. PATIENTS AND METHODS: We reviewed complete data from 233 patients with acute pancreatitis treated in our hospital during the period January 2017-January 2022. They were divided into three groups according to etiology: alcoholic acute pancreatitis (AAP), hyperlipidemic acute pancreatitis (HLAP), and alcoholic-hyperlipidemic acute pancreatitis (AHAP). General clinical data, co-morbidities, laboratory results, imaging data, and disease severity were analyzed and compared between groups. RESULTS: The proportion of male individuals in the AHAP group was significantly higher than that in the HLAP group (p<0.001). Age of onset was lower and the number of cases with antibiotic use was higher in the AHAP group than in the AAP group (p<0.05). Additionally, the average alcohol intake each time and weekly alcohol intake were also higher in the AHAP group than in the AAP group (p<0.05). Comparison of disease severity (moderate and severe acute pancreatitis, severe acute pancreatitis, and modified computed tomography severity index score) revealed the disease condition to be more severe in the AHAP group than in the AAP and HLAP groups (p<0.05). Accordingly, patients in the AHAP group had longer hospital stays than those in the other two groups (p<0.05). There were no significant differences in alcohol consumption, severity, or length of hospital stay in the AHAP group (p>0.05). CONCLUSIONS: The clinical characteristics of patients in the AHAP, AAP and HLAP groups were different, and the patients in the AHAP group were more likely to have a moderate to severe disease course, with longer hospital stay. As a new AP classification concept, AHAP would offer high significance for diagnosis, treatment, and prognosis.

Protocol for renal ischemia-reperfusion injury by flank incisions in mice.

Ischemia-reperfusion injury (IRI) contributes to acute kidney injury (AKI) and development of chronic kidney disease. We describe an IRI protocol for mice via flank incisions approach, using a pedicle clamp to cause ischemic injury. Compared with trans-abdominal approach, it is technically easier with lesser fluid loss and organ injury. Technical challenges during the dissection of renal pedicles are highlighted. For complete details on the execution of this protocol, please refer to Lai et al. (2014).

TARS2 variants causes combination oxidative phosphorylation deficiency-21: a case report and literature review.

OBJECTIVE: To explore the clinical characteristics and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous varians, and to improve clinicians' awareness of the disease. METHODS: The clinical performance, diagnosis and treatment process and gene characteristics of COXPD21 caused by TARS2 were reviewed and analyzed and reviewed combined with the literature. RESULTS: The proband was a girl, the first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay and intellectual disability，development backwardness after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. Two heterozygous varians in the TARS2 gene were detected by whole exome sequencing, one of which was c.1679(exon14) A > C (p.Asp560Ala) missense , which was derived from the mother, and the other was c.1036(exon10)C >T (p.Arg346Cys) missense variant, derived from the father, the child was diagnosed with COXPD21. The literature collected from the CNKI, Wanfang data and biomedical literature database (PubMed) until November 2021 were searched and reviewed with the key words "mitochondrial encephalomyopathy", "TARS2" and "combined oxidative phosphorylation deficiency type 21". A total of four complete domestic and foreign cases were collected from the literature search. CONCLUSION: COXPD21 onset by complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported at home and abroad.

Characterization of the complete mitochondrial genome of the fluke of turdus, Plagiorchis elegans, and phylogenetic implications.

Plagiorchis elegans (Trematoda: Digenea) is mainly parasitic in the intestines of vertebrate animals, including humans, causing irreversible pathological damage and herd-spherical influences. However, little information is available about its molecular epidemiology, population genetics, and phylogeny. In the present study, we sequenced, assembled, and annotated the complete mitochondrial (mt) genome of P. elegans. Combining with the available mitochondrial data of subclass Digenea, phylogenetic analysis was performed based on Bayesian inference (BI). These results showed that the complete length of P. elegans is 13,862 bp, including 12 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and one non-coding region (NCR). There was an obvious A + T content from 61.0% to 71.3% and the values of the Ka/Ks ratio ranged from 0.119 (cox1) to 1.053 (nad6). In the BI analysis, different from previous studies, phylogenetic analysis showed genus Glypthelmins was paraphyletic rather than monophyletic and had a closer relationship with Plagiorchis and Orientocreadium. Additionally, the BI tree also presented that the genus Echinostoma was monophyletic. Our results provided molecular data in the family Plagiorchiidae proposing new insight within Xiphidiata and Echinostomata.