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Abstract The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.

Abstract Background There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases the susceptibility of individuals to ovarian cancer (OC). However, the relationship between DM and OC remains largely unexplored. The objective of this study is to provide preliminary insights into the shared molecular regulatory mechanisms and potential biomarkers between DM and OC. Methods Multiple datasets from the GEO database were utilized for bioinformatics analysis. Single cell datasets from the GEO database were analysed. Subsequently, immune cell infiltration analysis was performed on mRNA expression data. The intersection of these datasets yielded a set of common genes associated with both OC and DM. Using these overlapping genes and Cytoscape, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then conducted on these core targets. Additionally, advanced bioinformatics analyses were conducted to construct a TF-mRNA-miRNA coregulatory network based on identified core targets. Furthermore, immunohistochemistry staining (IHC) and real-time quantitative PCR (RT-qPCR) were employed for the validation of the expression and biological functions of core proteins, including HSPAA1, HSPA8, SOD1, and transcription factors SREBF2 and GTAT2, in ovarian tumors. Results The immune cell infiltration analysis based on mRNA expression data for both DM and OC, as well as analysis using single-cell datasets, reveals significant differences in mononuclear cell levels. By intersecting the single-cell datasets, a total of 119 targets related to mononuclear cells in both OC and DM were identified. PPI network analysis further identified 10 hub genesincludingHSP90AA1, HSPA8, SNRPD2, UBA52, SOD1, RPL13A, RPSA, ITGAM, PPP1CC, and PSMA5, as potential targets of OC and DM. Enrichment analysis indicated that these genes are primarily associated with neutrophil degranulation, GDP-dissociation inhibitor activity, and the IL-17 signaling pathway, suggesting their involvement in the regulation of the tumor microenvironment. Furthermore, the TF-gene and miRNA-gene regulatory networks were validated using NetworkAnalyst. The identified TFs included SREBF2, GATA2, and SRF, while the miRNAs included miR-320a, miR-378a-3p, and miR-26a-5p. Simultaneously, IHC and RT-qPCR reveal differential expression of core targets in ovarian tumors after the onset of diabetes. RT-qPCR further revealed that SREBF2 and GATA2 may influence the expression of core proteins, including HSP90AA1, HSPA8, and SOD1. Conclusion This study revealed the shared gene interaction network between OC and DM and predicted the TFs and miRNAs associated with core genes in monocytes. Our research findings contribute to identifying potential biological mechanisms underlying the relationship between OC and DM.

It is well known that fabric of sand may significantly affect mechanical behaviors and liquefaction resistance of sand. Various optical techniques are currently utilized to visualize the fabric, especially the distribution of the long axis of soil particles. However, none of these methods provides an ideal solution in laboratory tests and in situ observation. In this study, anisotropy of magnetic susceptibility (AMS) was first proposed as a convenient and efficient way to evaluate the liquefaction of clean sand. At first, investigations with scanning electron microscopy (SEM) and AMS were simultaneously conducted on two groups of soil specimens with different initial fabrics to verify the feasibility of the AMS technique. Then, 80 in situ samples were collected to analyze the feature of liquefied and non-liquefied sand layers through AMS tests. It is clearly known from the test results that the natural sedimentary fabric was destroyed during liquefaction and the fabric anisotropy was greatly changed after liquefaction. The feasibility of evaluating soil fabric using the AMS survey was verified by the laboratory tests. Furthermore, the applicability of AMS in detecting liquefied layer in situ was confirmed for the first time.

Element tests, such as water retention tests and triaxial tests, are efficient and widely used methods for investigating the elementary hydro-mechanical behavior of unsaturated soil. In recent research, discrepancies observed in unsaturated test results using axis-translation techniques (ATTs) with ceramic disks and microporous membrane filters (MM filters) have indicated that misunderstandings might be hiding behind the perceived elementary behavior seen in element tests. In this study, triaxial tests with ceramic disks and MM filters were firstly conducted on specimens of unsaturated completely decomposed granite sand, referred to as Masado in Japan, to compare the influence of different techniques on the test results. Then a soil–water-air coupled finite element-finite difference (FE-FD) method, based on a newly proposed unsaturated/saturated constitutive model coupled with a deformation-dependent water retention curve (WRC), was utilized to simulate triaxial tests as boundary value problems (BVPs) because of the non-uniform deformation of the specimens. Drained/vented triaxial tests showed that the stress–strain relation of Masado is basically the same regardless of the applied technique, while the amount of drainage discharge and degree of saturation during the shearing stage are quite different. The calculated average stress–strain relation basically reproduced a tendency similar to that of the tests. It was also shown from the calculation that the ATT with ceramic disks or MM filters significantly influences the distributions of saturation and stress within the specimens during shearing. It should be emphasized that unsaturated triaxial tests with the ATT are basically BVPs instead of so-called element tests.

ObjectiveAs one of the cancers that seriously threatens women’s health, ovarian cancer has a high morbidity and mortality rate. Surgery and chemotherapy are the basic treatment strategies for ovarian cancer, and chemotherapy resistance is a significant factor in affecting the prognosis, survival cycle, and recurrence of ovarian cancer. This article aims to analyze articles about ovarian cancer and drug resistance via bibliometric software, offering new ideas and directions for researchers in this field.MethodsBoth Citespace and Vosviewer are bibliometric software on the Java platform. Articles were collected on ovarian cancer and drug resistance in the Web of Science Core Collection database from 2013 to 2022. The countries, institutions, journals, authors, keywords, and references were analyzed, and the development status of this field was indicated from multiple perspectives.ResultsStudies on ovarian cancer and drug resistance generally showed an increasing trend from 2013 to 2022. The People’s Republic of China and Chinese institutions contributed more to this field. Gynecologic Oncology published the most articles, and the journal with the most citations was Cancer Research. Li Li was the author with the most publications, and Siegel RL was the author with the most citations. Through burst detection, it can be found that the research hotspots in this field mainly focused on the in-depth exploration of the drug resistance mechanism of ovarian cancer and the progress of PARP inhibitors and bevacizumab in the treatment of ovarian cancer.ConclusionsMany studies on the mechanism of drug resistance in ovarian cancer have been discovered; however, the deeper mechanism remains to be explored. Compared with traditional chemotherapy drugs, PARP inhibitors and bevacizumab have shown better efficacy, but PARP inhibitors have initially shown drug resistance. The future direction of this field should be to overcome the resistance of existing drugs and actively develop new ones.

Abstract Background We aimed to appraise the impact of the changing national childbirth policy since 2002, currently allowing two children per family, on obstetric workload in a regional referral center in China. Methods In a retrospective cohort study, temporal changes were examined in relation with maternal demographics, incidence of women with high risk pregnancies and resource statistics in our hospital in managing singleton viable pregnancies (birth from 28 weeks gestational age onwards) for the period 2005–2017. Results During this 13-year period, the number of singleton livebirths from 28 weeks gestational age onwards was 49,479. Annual numbers of births increased from 1,941 to 2005 to 5,777 in 2017. There were concomitant and significant increases in the incidence of multiparous women (10.6–50.8 %), of age ≥35 years (6.5–24.3 %), with prior caesarean Sec. (2.6–23.6 %), with ≥3 previous pregnancy terminations (1.0–4.9 %), with pre-gestational diabetes (0.2–0.9 %), and with chronic hypertension (0.2–1.2 %). There were associated increases in beds and staff complement and reduced average hospital stay. Nevertheless, while the workload of medical staff remained stable with increasing staff complement, that of midwives increased significantly as reflected by the total births: midwife ratio which increased from 194.1:1 to 320.9:1 (p

Abstract Background Chinese population has a high prevalence of chronic hepatitis B virus (HBV) infection, the impact of which on pregnancy outcome remains controversial. A single-center retrospective cohort study was performed in Kunming, a multi-ethnic city in south-western China to examine this issue. Methods The singleton pregnancies delivering at ≥28 weeks gestation under our care in 2005–2017 constituted the study cohort. Maternal characteristics and pregnancy outcome were compared between mothers with and without seropositivity for hepatitis B surface antigen (HBsAg) determined at routine antenatal screening. Results Among the 49,479 gravidae in the cohort, the 1624 (3.3%) HBsAg seropositive gravidae had a lower incidence of nulliparity (RR 0.963, 95% CI 0.935–0.992) and having received tertiary education (RR 0.829, 95% CI 0.784–0.827). There was no significant difference in the medical history, pregnancy complications, or labor or perinatal outcome, except that HBV carriers had significantly lower incidence of labor induction (RR 0.827, 95% CI 0.714–0.958) and of small-for-gestational age (SGA) infants (RR 0.854, 95% CI 0.734–0.994). On regression analysis, maternal HBV carriage was independently associated with spontaneous labor (aRR 1.231, 95% CI 1.044–1.451) and reduced SGA infants (aRR 0.842, 95% CI 0.712–0.997). Conclusions Our 3.3% prevalence of maternal HBV infection was around the lower range determined in the Chinese population. The association with spontaneous labor and reduced SGA infants could have helped to promote the perpetuation of the infection through enhanced survival of the offspring infected at birth, thus explaining the high prevalence in the Chinese population.

Abstract Background Jowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complications or diabetic nephropathy (DN) in traditional medicine clinics. However, the underlying therapeutic mechanisms of JSD are still unclear. Methods Streptozotocin (STZ)-induced DN mice were administered 100 and 500 mg/kg JSD for 4 weeks, and the therapeutic mechanisms and targets of JSD were analyzed by network pharmacology and gut microbiota analyses. Results JSD significantly decreased the increase in food and water intake, urine volume, fasting blood glucose, serum glucose and triglyceride levels, and urinary albumin excretion. JSD administration significantly increased the decrease in insulin secretion and creatinine clearance and reduced the structural damage to the kidney tissues. Moreover, JSD administration significantly inhibited the expression of protein kinase C-alpha (PKC-α), transforming growth factor beta-1 (TGF-β1), α-smooth muscle actin (α-SMA), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the kidney tissues of DN mice, while it significantly increased the phosphorylation of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). In the network pharmacological analysis, JSD obviously influenced phosphatase binding, protein serine/threonine kinase, and mitogen-activated protein kinase (MAPK)-related signaling pathways. Our data suggest that JSD can improve symptoms in STZ-induced DN mice through the inhibition of kidney dysfunction, in particular, by regulating the PKCα/PI3K/Akt and NF-κB/α-SMA signaling pathways. Gut microbiota analysis can help to discover the pharmaco-mechanisms of the influence of JSD on bacterial diversity and flora structures in DN. Conclusion JSD can improve the symptoms of DN, and the underlying mechanism of this effect is renal protection through the inhibition of fibrosis and inflammation. JSD can also change bacterial diversity and community structures in DN.

Energy is often dissipated and released in the process of rock deformation and failure. To study the energy evolution of rock discontinuities under cyclic loading and unloading, cement mortar was used as rock material and a CSS-1950 rock biaxial rheological testing machine was used to conduct graded cyclic loading and unloading tests on Barton’s standard profile line discontinuities with different joint roughness coefficients (JRCs). According to the deformation characteristics of the rock discontinuity sample, the change of internal energy is calculated and analyzed. The experimental results show that under the same cyclic stress, the samples harden with the increase in the number of cycles. With the increase of cyclic stress, the dissipated energy density of each stage gradually exceeds the elastic energy density and occupies a dominant position and increases rapidly as failure becomes imminent. In the process of increasing the shear stress step-by-step, the elastic energy ratio shows a downward trend, but the dissipated energy is contrary to it. The energy dissipation ratio can be used to characterize the internal damage of the sample under load. In the initial stage of fractional loading, the sample is in the extrusion compaction stage, and the energy dissipation ratio remains quasi-constant; then the fracture develops steadily, the damage inside the sample intensifies, and the energy dissipation ratio increases linearly (albeit at a low rate). When the energy storage limit is reached, the growth rate of energy dissipation ratio increases and changes when the stress level reaches a certain threshold. The increase of the roughness of rock discontinuity samples will improve their energy storage capacity to a certain extent.

Bekhogainsam decoction (BHID), a representative prescription for the treatment of diabetes mellitus (DM) and diabetic complications in both traditional Korean and Chinese medicine, was examined for its ability to ameliorate diabetic nephropathy (DN), and its mechanism of action was evaluated by metabolomics, gut microbiota, and network pharmacology. In this study, male specific pathogen-free C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ, 100 mg/kg) once per day for 3 days consecutively, and were then orally administered BHID at 100 and 500 mg/kg, and metformin at 250 mg/kg once per day for 4 weeks. Our results showed that the administration of BHID to mice with STZ-induced DN prevented physiological and serological changes, structural damage, and kidney dysfunction. Based on a metabolomics test with serum, the profoundly altered metabolites in the BHID treatment group were identified. Thirty-six BHID-related proteins and four signaling pathways, including valine, leucine, and isoleucine biosynthesis, nicotinate and nicotinamide metabolism, tryptophan metabolism, and alanine, aspartate, and glutamate metabolism pathways, were explored. Principal coordinates analysis (PCoA) of the gut microbiota revealed that BHID treatment significantly affected the flora composition. In addition, the network pharmacology analysis revealed that BHID acted through phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and MAPK-related protein targets. Our findings on the anti-DN effects of BHID and its mechanism of action, from the perspective of systems biology, have provided scientific evidence to support the clinical treatment of patients with diabetes, and implied that BHID has the potential to prevent the progression of DN.

Our study was conducted to investigate the effects of the fruits of Lycium chinense Mill. (Lycii Fructus, LF) and its bioactive compound, betaine, on muscle differentiation and mitochondrial biogenesis in C2C12 cells. LF extract and betaine was analyzed by high-performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC-1α), sirtuin-1(Sirt-1), nuclear respiratory factor-1 (NRF-1), transcription factor A, mitochondrial (TFAM) and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), were determined in cellular or mitochondrial levels by quantitative polymerase chain reaction (qPCR) or Western blot, respectively. The glucose levels and total ATP contents were measured by the glucose consumption in a culture medium, cellular glucose uptake and ATP assays. LF extract at 4 mg/ml and betaine at 2 and 5 mM significantly increased the expression of MyHC in C2C12 myotubes, compared with non-treated cells. LF extract and betaine significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM mRNA and protein in the myotubes, as well as phosphorylation of AMPK and ACC. Furthermore, LF extract and betaine significantly increased the mitochondrial protein contents, as the TFAM and NRF-1 expressions were increased. LF extract and betaine also significantly increased the glucose uptake and ATP contents in the myotubes. The LF extract contained 3.18% betaine was quantitated by HPLC. LF extract and betaine enhanced muscle differentiation and energy metabolism through the up-regulation of mitochondrial biogenesis-regulating factors, suggesting that LF extract and betaine can help to prevent the dysfunction of skeletal muscle.

This study aimed to (1) investigate effects of reducing postpartum dietary energy level for cows after a 0-d dry period (DP) on resumption of ovarian cyclicity and reproductive performance, (2) relate days open with other reproductive measures, and (3) relate onset of luteal activity (OLA) and days open with metabolic status in early lactation. Holstein-Friesian dairy cows were randomly assigned to 1 of 3 transition treatments: no DP and low postpartum dietary energy level from 22 days in milk( DIM )onwards (0-d DP (LOW)) (n = 42), no DP and standard postpartum dietary energy level (0-d DP (STD)) (n = 43), and a short DP and standard postpartum dietary energy level (30-d DP (STD)) (n = 43). Milk progesterone concentration was determined three times per week until 100 DIM. Plasma metabolite and hormone concentrations were measured weekly until week 7 postpartum. Reducing postpartum dietary energy level in older cows (parity ≥ 3) after no DP and 22 DIM did not affect milk production but prevented a positive energy balance and shortened the interval from calving to OLA. In addition, services per pregnancy and days open were reduced in cows of parity ≥ 3 on 0-d DP (LOW), compared with cows of parity ≥ 3 with 0-d DP (STD), but not in cows of parity 2.

Although flavonoids or yeast have been used as feed additives to improve the production efficiency and health of adult cattle, little information is available on their effects on rumen fermentation in calves. The objective of this study was to investigate the effects of feed supplementation with mulberry leaf flavonoids and Candida tropicalis on performance, blood parameters, and rumen fermentation characteristics during pre-weaning and post-weaning periods. Forty-eight Holstein calves were used in a four-groups trial and were supplemented with (1) no yeast or flavonoids (CON), (2) active dry yeast (ADY; C. tropicalis, 5.0 × 109 CFU/d), (3) flavonoids (FLA; 3 g/d), or (4) yeast and flavonoids (YF; C. tropicalis, 5.0 × 109 CFU/d; flavonoids, 3 g/d). The feeding strategy was as follows: milk replacer was offered at 12% of body weight in two meals per calf each day at age 21 d, and a gradual weaning process was adopted at age 50 to 56 days. Data of daily feed intake, body weight, and serum and rumen fermentation parameters were obtained at 28, 42, 56, and 80 d ages, respectively. A significant time effect and interaction between treatment and time was found for average daily gain, feed efficiency, total volatile fatty acid concentration, and proportion of propionate in calves (p < 0.05). Average daily gain and feed efficiency increased during post-weaning and overall periods for calves in FLA and YF groups compared with CON and ADY groups (p < 0.05). A reduction of fecal scores with supplementation was found in FLA and YF groups (p < 0.05). Rumen fluid pH and ammonia nitrogen concentration remained constant across the groups, whereas total volatile fatty acid concentration and molar proportion of propionate significantly increased during the pre-weaning and overall periods in FLA and YF groups (p < 0.05). Calves in YF group had the highest serum concentrations of IgG and IgA during the overall period (p < 0.05). Additionally, serum β-hydroxybutyric acid concentration was higher in ADY and FLA groups during the post-weaning period (p < 0.05). Supplementation with C. tropicalis showed little effect on increasing growth performance and health compared with flavonoids alone. Meanwhile, the combination of C. tropicalis and flavonoids was not synergistic with respect to improving health and rumen fermentation compared with use of flavonoids alone in pre- and post-weaning calves (p > 0.05).

Control of temperature and duration of partial carbonization for Chinese medicines have been mainly based on experience of the processors. No quantitative methods and parameters are available that can be used to precisely control the temperature and determine the energy changes during the process. In our research, with a simulated atmosphere air condition, the partial carbonization processes of three Chinese herb medicines rhubarb, moutan and burnet were simulated at different heating rates (5, 10 and 20°C • min-1) and analyzed by thermal gravimetric analysis (TGA) to quantify the upper limits of the temperature. The activation energy was calculated with Friedman, Kissinger-Akahira-Sunose (KAS) method and Ozawa-Flynn-Wall (OFW) methods in iso-conversional models and independent parallel reaction model (IPR). The upper temperatures were calculated to be 280, 184 and 246°C for rhubarb, moutan and burnet, respectively, at corresponding conversion rates of 0.4, 0.2 and 0.1. Calculation of the activation energy has been found impossible with the IPR model. Results obtained from the three iso-conversional methods were different. For rhubarb and burnet, the conversion rates at the upper temperature limits were at the highest or second highest activation energy, while for moutan, it was at the lowest value of activation energy. These results confirmed scientific rationales of traditional Chinese medicine theory that rhubarb and burnet be prepared at high temperature and moutan be prepared at medium temperature. Application of thermal analysis techniques would broaden and deepen traditional Chinese medicine research, and are applicable to the processing of medicinal materials including traditional Chinese medicines. Results obtained from the study could provide new ideas and methods for research to modernize the preparation of traditional Chinese medicines.

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.