Preoperative blood urea nitrogen-to-serum albumin ratio for prediction of in-hospital mortality in patients who underwent emergency surgery for acute type A aortic dissection.

The study aimed to assess the predictive value of blood urea nitrogen (BUN)-to-albumin ratio (BA-R) for in-hospital mortality in patients undergoing emergency surgery for acute type A aortic dissection (ATAAD). Patients who were diagnosed with ATAAD and underwent emergency surgery within 48 hours of onset at our hospital between January 2015 and December 2021 were included in this study. The primary endpoint of this study was postoperative in-hospital mortality (POIM). The data of the survivors and non-survivors were retrospectively compared analyses. A total of 557 ATAAD patients were included, with 505 survivors and 52 non-survivors. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (P < 0.001). Univariate regression analysis showed that preoperative BA-R, serum creatinine level, SA level, D-dimer level, age, myocardial ischemia, cerebral ischemia, and aortic clamp time were risk factors for POIM. In addition, multivariable regression analysis showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). Receiver operating characteristic curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (area under the curve =0.874). The sensitivity and specificity of preoperative BA-R in predicting the POIM of patients who underwent emergency surgery for ATAAD were 84.6% and 71.3%, respectively (95% confidence interval, 0.829-0.919; P < 0.001). In conclusion, Preoperative BA-R is a simple, rapid, and potentially useful prognostic indicator of POIM in patients with ATAAD. BAR: Blood urea nitrogen-to-albumin ratio, BUN: Blood urea nitrogen, SA: Serum albumin, REF: Reference. The aim of this study was to evaluate the prognostic value of BA-R for the prediction of postoperative in-hospital mortality in patients who underwent emergency surgery for ATAAD. A total of 557 patients with ATAAD were enrolled, and 505 survived while 52 did not. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (0.27 [0.18, 0.46] vs. 0.12 [0.10, 0.16]mmol/g; P < 0.001). The study showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). ROC curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (AUC = 0.874) and the sensitivity and specificity were 84.6% and 71.3%, respectively (95% CI, 0.829-0.919; P < 0.001). We believe that our study makes a significant contribution to the literature because we found preoperative BA-R to be a simple, rapid, and potentially useful prognostic indicator of postoperative in-hospital mortality in patients with ATAAD.

Insight into the probability of ethoxy(pentafluoro)cyclotriphosphazene (PFPN) as the functional electrolyte additive in lithium-sulfur batteries.

Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.

Physiologically based pharmacokinetic modeling to predict maternal pharmacokinetics and fetal carbamazepine exposure during pregnancy.

Carbamazepine is an antiepileptic drug commonly used in pregnant women, during which the physiological changes may affect its efficacy. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) model of carbamazepine and its active metabolite carbamazepine-10,11-epoxide, and simulate maternal and fetal pharmacokinetic changes of carbamazepine and carbamazepine-10,11-epoxide in different trimesters and propose dose adjustment. We established pregnancy PBPK models for carbamazepine and carbamazepine-10,11-epoxide in PK-Sim® and Mobi® and validated the models with observed data from clinical reports. The placental transfer parameters obtained using different methods were also imported into the model and compared with the observed data to establish and validate fetal pharmacokinetic curves. The simulated results showed that mean steady-state trough plasma concentration of carbamazepine decreased by 27, 43.1, and 52 % during the first, second, and third trimesters, respectively. Therefore, to achieve an optimum therapeutic concentration, administering at least 1.4, 1.8, and 2.1 times the baseline dose of carbamazepine in the first, second, and third trimesters, respectively can be used as a dose reference. In conclusion, this study established and validated a pregnancy PBPK model of carbamazepine and carbamazepine-10,11-epoxide to assess exposure in pregnant women and fetuses, which provided a reference for the dosage adjustment of carbamazepine during pregnancy.

Epigenetic regulation and epigenetic memory resetting during plant rejuvenation.

Reversal of plant developmental status from the mature to the juvenile phase, thus leading to the restoration of the developmental potential, is referred to as plant rejuvenation. It involves multilayer regulation, including resetting gene expression patterns, chromatin remodeling, and histone modifications, eventually resulting in the restoration of juvenile characteristics. Although plants can be successfully rejuvenated using some forestry practices to restore juvenile morphology, physiology, and reproductive capabilities, studies on the epigenetic mechanisms underlying this process are in the nascent stage. This review provides an overview of the plant rejuvenation process and discusses the key epigenetic mechanisms involved in DNA methylation, histone modification, and chromatin remodeling in the process of rejuvenation, as well as the roles of small RNAs in this process. Additionally, we present new inquiries regarding the epigenetic regulation of plant rejuvenation, aiming to advance our understanding of rejuvenation in sexually and asexually propagated plants. Overall, we highlight the importance of epigenetic mechanisms in the regulation of plant rejuvenation, providing valuable insights into the complexity of this process.

Characterization of pollen tube development in distant hybridization of Chinese cork oak (Quercus variabilis L.).

MAIN CONCLUSION: This work mainly found that the stigma and style of Q. variabilis did not completely lose the specific recognition towards heterologous pollen, a fact which is different from previous studies. Quercus is the foundation species in the Northern Hemisphere, with extreme prevalence for interspecific hybridization. It is not yet entirely understood whether or how the pollen tube-female tissue interaction contributes to the "extensive hybridization" in oaks. Pollen storage conditions correlate with distant hybridization. We conducted hybridization experiments with Q. variabilis as female and Q. variabilis and Q. mongolica as male parents. And the differences in pollen tube (PT) development between intra- and distant interspecific hybridization were studied by fluorescence microscopy and scanning electron microscopy (SEM). Our results showed that -20 °C allowed pollen of both species to maintain some viability. Both Q. variabilis and Q. mongolica pollen germinated profusely on the stigmas. SEM results indicated that in the intraspecific hybridization, Q. variabilis pollen started to germinate at 6 h after pollination (hap), PTs elongated significantly at 12 hap, and entered the stigma at 24 hap. By contrast, Q. mongolica pollen germinated at 15 hap, and the PTs entered the stigma at 27 hap. By fluorescence microscopical studies it was observed that some PTs of Q. variabilis gathered at the style-joining at 96 hap, unlike the Q. mongolica which reached the style junction at 144 hap. The above results indicate that the abundant germination of heterologous pollen (HP) on the stigma and the "Feeble specificity recognition" of the stigma and transmitting tract to HP may create opportunities for the "extensive hybridization" of oaks. This work provides a sexual developmental reference for clarifying the causes of Quercus "extensive hybridization".

The m6A reader YTHDF1 attenuates fulminant hepatitis via MFG-E8 translation in an m6A dependent manner.

Background and Aims: N6-methyladenosine (m6A) is the most common post-transcriptional modification of RNA in eukaryotes, which has been demonstrated to play important roles in various biological processes. However, its roles in fulminant hepatitis remain largely unknown. In the current study, YTHDF1 expression was found to be significantly downregulated in the livers among patients, as well as murine models with fulminant hepatitis versus normal controls. Thus, we hypothesized that YTHDF1 protects against fulminant hepatitis and investigated the underlying molecular mechanisms. Methods: Fulminant hepatitis was induced by D-GalN/LPS in conventional YTHDF1 knockout (YTHDF1-/-) mice, hepatocyte-specific YTHDF1 overexpression (AAV8- YTHDF1) mice, and corresponding control mice. Primary hepatocytes were cultured and subjected to LPS insult in vitro. Hepatic histology, cell death, oxidative stress and mitochondrial function were examined to assess liver damage. The molecular mechanisms of YTHDF1 function were explored using multi-omics analysis. Results: Ablation of YTHDF1 exacerbated hepatic apoptosis and reactive oxygen species (ROS) production and increased the number of aberrant mitochondria, while YTHDF1 overexpression resulted in the opposite effects. Multiomics analysis identified MFG-E8 as the direct target of YTHDF1. YTHDF1 augmented the translation of MFG-E8 in an m6A-dependent manner without effect on its mRNA expression, thereby restoring mitochondrial function. Additionally, administration of MFG-E8 almost completely reversed the YTHDF1 deficiency-mediated exacerbation of liver injury. Conclusions: The current study suggested that the m6A reader YTHDF1 alleviates cell death, enhances antioxidant capacity and restores mitochondrial function in fulminant hepatitis by promoting MFG-E8 protein translation in an m6A-dependent manner.

Physiologically-Based Pharmacokinetic Modeling of Anti-Tumor Necrosis Factor Agents for Inflammatory Bowel Disease Patients to Predict the Withdrawal Time in Pregnancy and Vaccine Time in Infants.

Anti-tumor necrosis factor (anti-TNF) agents are widely applied for patients with inflammatory bowel disease (IBD); however, the timing of the last dosing for IBD pregnancy and time to elimination in anti-TNF agent-exposed infants is controversial. This study aimed to determine the optimal timing for the last dosing of anti-TNF agents (infliximab, adalimumab, and golimumab) in pregnant women with IBD, as well as to investigate the recommended vaccine schedules for infants exposed to these drugs. A physiologically-based pharmacokinetic (PBPK) model of anti-TNF agents was built for adults and extrapolated to pregnant patients, fetuses, and infants. The PBPK models successfully predicted and verified the pharmacokinetics (PKs) of infliximab, adalimumab, and golimumab in pregnancy, fetuses, and infants. The predicted PK data were within two-fold of the observed data. The simulated results were used as timing advice. According to the dose of administration, the suggested timing of the last dosing for infliximab, adalimumab, and golimumab is successfully provided based on PBPK predictions. PBPK models indicated that, for infants, the advocated timing of vaccination is 12, 8, and 5 months after birth for infliximab, adalimumab, and golimumab, respectively. Our study illustrated that PBPK models can provide a valuable tool to predict the PKs of large macromolecules in pregnant women, fetuses, and infants, ultimately informing drug-treatment decisions for pregnancy and vaccination regimens for infants.

Physiologically based pharmacokinetic model combined with reverse dose method to study the nephrotoxic tolerance dose of tacrolimus.

Nephrotoxicity is the most common side effect that severely limits the clinical application of tacrolimus (TAC), an immunosuppressive agent used in kidney transplant patients. This study aimed to explore the tolerated dose of nephrotoxicity of TAC in individuals with different CYP3A5 genotypes and liver conditions. We established a human whole-body physiological pharmacokinetic (WB-PBPK) model and validated it using data from previous clinical studies. Following the injection of 1 mg/kg TAC into the tail veins of male rats, we developed a rat PBPK model utilizing the drug concentration-time curve obtained by LC-MS/MS. Next, we converted the established rat PBPK model into the human kidney PBPK model. To establish renal concentrations, the BMCL5 of the in vitro CCK-8 toxicity response curve (drug concentration range: 2-80 mol/L) was extrapolated. To further investigate the acceptable levels of nephrotoxicity for several distinct CYP3A5 genotypes and varied hepatic function populations, oral dosing regimens were extrapolated utilizing in vitro-in vivo extrapolation (IVIVE). The PBPK model indicated the tolerated doses of nephrotoxicity were 0.14-0.185 mg/kg (CYP3A5 expressors) and 0.13-0.155 mg/kg (CYP3A5 non-expressors) in normal healthy subjects and 0.07-0.09 mg/kg (CYP3A5 expressors) and 0.06-0.08 mg/kg (CYP3A5 non-expressors) in patients with mild hepatic insufficiency. Further, patients with moderate hepatic insufficiency tolerated doses of 0.045-0.06 mg/kg (CYP3A5 expressors) and 0.04-0.05 mg/kg (CYP3A5 non-expressors), while in patients with moderate hepatic insufficiency, doses of 0.028-0.04 mg/kg (CYP3A5 expressors) and 0.022-0.03 mg/kg (CYP3A5 non-expressors) were tolerated. Overall, our study highlights the combined usage of the PBPK model and the IVIVE approach as a valuable tool for predicting toxicity tolerated doses of a drug in a specific group.

Physiologically Based Pharmacokinetic Modeling Characterizes the Drug-Drug Interaction Between Saxagliptin and Rifampicin in Patients With Renal Impairment.

The aim of the present study is to develop physiologically based pharmacokinetic (PBPK) models for saxagliptin and its active metabolite, 5-hydroxy saxagliptin, and to predict the effect of coadministration of rifampicin, a strong inducer of cytochrome P450 3A4 enzymes, on the pharmacokinetics of saxagliptin and 5-hydroxy saxagliptin in patients with renal impairment. The PBPK models of saxagliptin and 5-hydroxy saxagliptin were developed and validated in GastroPlus for healthy adults with or without rifampicin and adults with varying renal functions. Then, the effect of renal impairment combined with drug-drug interaction on saxagliptin and 5-hydroxy saxagliptin pharmacokinetics was investigated. The PBPK models successfully predicted the pharmacokinetics. For saxagliptin, the prediction suggests that rifampin greatly weakened the effect of renal impairment on reducing clearance, and the inductive effect of rifampin on parent drug metabolism seems to be increased with an increase in the degree of renal impairment severity. For patients with the same degree of renal impairment, rifampicin would have a slightly synergistic effect on the increase of 5-hydroxy saxagliptin exposure compared with dosed alone. There is an unsignificant decline for the saxagliptin total active moiety exposure values in patients with the same degree of renal impairment. It seems that patients with renal impairment are unlikely to require additional dose adjustments when coadministered with rifampicin, compared with saxagliptin alone. Our study provides a reasonable approach to explore unknown DDI potential in renal impairment.

Arthroscopic Autologous Coracoacromial Ligament Augment Technique for Particle Thickness of Rotator Cuff with at Least Two Years Follow-Up.

OBJECTIVE: Patch technology has been the new technique in the treatment of partial thickness of the rotator cuff tear (PTRCTs) to address the limitation of traditional techniques. Compared with allogeneic patches and artificial materials, coracoacromial ligament is obviously closer to their own biology. The purpose of the study was to evaluate the functional and radiographic outcomes following arthroscopic autologous coracoacromial ligament augment technique for treatment of PTRCTs. METHOD: This study included three female patients with PTRCTs who underwent arthroscopy operation in 2017 with an average age of 51 years (range from 50 to 52 years). The coracoacromial ligament implant was attached to the bursal side surface of the tendon. The clinical results were evaluated by American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST), acromiohumeral distance (AHD) and muscle strength before and 12 months after operation. Magnetic resonance imaging (MRI) was performed 24 months after operation to assess the integrity of the anatomical structure of the original tear site. RESULT: The average ASES score improved significantly from 57.3 preoperatively to 95.0 at 1-year follow-up. The strength improved significantly from grade 3 preoperatively to grade 5 at 1 year. Two of three patients underwent the MRI at 2-year follow-up. Radiographic released the complete healing of rotator cuff tear. No implant-related serious adverse events were reported. CONCLUSION: The new technique of using autogenous coracoacromial ligament patch augment provides good clinical results on patients with PTRCTs.

Establishment and validation of a predictive nomogram for the risk of premalignant lesions in children with choledochal cyst.

Background: Choledochal cyst (CDC) increases the risk (2.5%-30%) of malignancy. Metaplasia and dysplasia have been recognized as premalignant lesions among CDCs. This study aimed to evaluate the risk factors of metaplasia and dysplasia in CDC children. Methods: Two hundred and ten CDC children who underwent cyst excision and Roux-en-Y hepaticojejunostomy at our institution between July 2020 and November 2021 were included and randomly divided into the training set and validation set. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of premalignant lesions in the training set and build a predictive nomogram. The performance and discriminatory abilities of the nomogram were further assessed and validated in the validation set. Results: Of the 210 CDC children, 78 (37.1%) patients developed premalignant lesions. Age (OR, 1.011, 95%CI, 1.000-1.022, P = 0.046), symptoms duration (OR, 1.021, 95%CI, 1.001-1.042, P = 0.036), cyst diameter (OR, 1.737, 95%CI, 1.328-2.273, P < 0.001), recurrent attacks of biliary pancreatitis (OR, 3.653, 95%CI, 1.205-11.076, P = 0.022), and biliary operation history (OR, 5.860, 95%CI, 1.268-27.084, P = 0.024) were identified as independent risk factors. Based on these predictors, a predictive nomogram was generated. The AUC of the nomogram was 0.873 in the training set and 0.793 in the validation set, indicating that it was robust and well calibrated. Conclusions: A novel nomogram to the individualized risk of premalignant lesions in CDC children was successfully built, on the basis of age, symptoms duration, cyst diameter, recurrent attacks of biliary pancreatitis, and biliary operation history. This nomogram, combined with the final pathological results, can help clinicians to develop more efficient follow-up strategies for the high-risk children with CDC.

Physiologically-Based Pharmacokinetic Modeling of Omalizumab to Predict the Pharmacokinetics and Pharmacodynamics in Pediatric Patients.

Omalizumab is widely used in clinical practice; however, knowledge gaps in the dosage of omalizumab for children aged 2-6 years with moderate-to-severe persistent allergic asthma have been identified. The aim of this study was to explore dosing regimens for moderately-to-severely allergic pediatric patients aged 2-6 years. The physiologically-based pharmacokinetic (PBPK) model of omalizumab was developed and verified in adult patients, extrapolated to pediatric patients, and simulated for omalizumab by adding two observation chambers (free IgE and total IgE). The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (Cmax ) were between 0.5 and 2.0, and the average folding error and the absolute average folding error values for all concentration-time data points were 1.09 and 1.48, respectively. The PBPK model combined with pharmacokinetic/pharmacodynamic analysis of omalizumab demonstrated that both the model-derived dose and the original dose could control the average free IgE of 2-6-year-old children with moderate-to-severe allergic asthma below 25 ng/mL, and some of the model-derived doses were lower. This conclusion provides a basis for the selection of dosage in clinical practice reference.

Application of PBPK modeling in predicting maternal and fetal pharmacokinetics of levetiracetam during pregnancy.

Levetiracetam is currently being used to treat epilepsy in pregnant women. The plasma concentration of levetiracetam drops sharply during pregnancy, and the inability of pregnant women to maintain therapeutic concentrations can lead to seizures. This study aimed to predict the changes in fetal and maternal plasma exposure to levetiracetam during pregnancy and provide advice on dose adjustment. The physiology-based pharmacokinetics (PBPK) model was developed using PK-Sim and Mobi software, and validated following comparison of the observed plasma concentration and pharmacokinetic parameters. The levetiracetam PBPK model for mother and the fetus at various stages of pregnancy was successfully established and verified. Predictions indicated that the area under the steady-state concentration-time curve for levetiracetam decreased to 83, 62, and 67% of baseline values in the first, second, and third trimesters, respectively. Based on PBPK predictions, the recommended dose of levetiracetam is 1.2, 1.6, and 1.5 times the baseline dose in the first, second, and third trimesters, respectively, not exceeding 4000 mg/day in the third trimester due to fetal safety. The levetiracetam PBPK model for pregnancy was successfully developed and validated, and could provide alternative levetiracetam dosing regimens across the stages of pregnancy.

Coexistence of Non-Hodgkin's Lymphoma and Acute Myeloid Leukemia at Initial Diagnosis: A Case Report.

Non-Hodgkin's lymphoma and acute myeloid leukemia are both hematological malignancies that rarely coexist at the time of initial diagnosis. We present a case of non-Hodgkin lymphoma and acute myeloid leukemia diagnosed on the first admission. BACKGROUND: Lymphoma and leukemia, both malignant hematological cancers, are primarily different diseases, with a majority of cases originating independently. The co-occurrence of lymphoma and leukemia at the time of the first diagnosis is extremely rare, and few relevant reports exist in the medical literature. We describe a case of a patient with non-Hodgkin's lymphoma and acute myeloid leukemia, a very rare occurrence. CASE REPORT: A 57-year-old man complained of fatigue and neck tumors. A physical examination revealed several enlarged superficial lymph nodes throughout the body. On admission, routine blood tests revealed anemia, thrombocytopenia, and normal counts of white blood cells. Cytology of two cervical lymph nodes indicated non- Hodgkin's lymphoma, 18F-PET/CT: multiple enlarged lymph nodes with hypermetabolism, diffuse hypermetabolism of the bone marrow, suggesting lymphoma infiltration in the bone marrow, and a bone marrow biopsy revealed acute myeloid leukemia. Ultimately, the patient was diagnosed with non-Hodgkin's lymphoma and acute myeloid leukemia. CONCLUSION: Primary bilineage hematological malignancies are rare, and the mechanism underlying their incidence is unknown. Infiltration of the bone marrow by lymphoma or leukemia can result in diffuse hypermetabolism, mostly diagnosed via bone marrow biopsy.

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus-infected patients.

BACKGROUND: Following initiation of combined antiretroviral therapy, the majority of human immunodeficiency virus-infected patients experience immune reconstitution indicated by virologic suppression and an increase in peripheral CD4+ T-cell counts. Some patients may suffer from low-level viremia, which was reported to be significantly associated with acquired immunodeficiency syndrome cases, virologic failure, and death. We aimed to further investigate the influence of low-level viremia on CD4+ T-cell count. METHODS: In our study, we included human immunodeficiency virus-seropositive patients on combined antiretroviral therapy, for at least 6 months, who received at least one assessment of human immunodeficiency virus plasma viral load and CD4+ cell count every 6 months, from January 2009 to January 2019. The copy-year viremia was determined by calculating the area under the curve of the plasma human immunodeficiency virus viral load. RESULTS: When comparing patients with a mean CD4+ cell count <200 cells/µL, there was no significant difference between patients with a mean viral load <1000 copies/mL and patients with a mean viral load ≥1000 copies/mL (p = 0.219). Among those with a mean viral load <1000 copies/mL, a higher proportion of patients had a mean CD4+ cell count ≥500 cells/µL (p < 0.001). The mean CD4+ cell count of patients with copy-years viremia (log10) <4 (577.7, interquartile range 429.2-736.7) was significantly higher than that of patients with copy-years viremia (log10) ≥4 (443.3, interquartile range 319.0-558.4) (p < 0.001). In multivariate logistic regression analysis, we observed that malignancy without history, lower copy-years viremia, and high nadir CD4+ cell count were independent predictors of mean CD4+ cell count ≥500 cells/µL. CONCLUSION: Human immunodeficiency virus-infected patients with a history of malignancy, high copy-year viremia, and lower nadir CD4+ cell counts should be monitored carefully in clinical settings.

Efficacy and safety of Chinese herbal medicine Danggui Sini decoction for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) often causes joint pain, weakness and mobility disorders, which seriously affects people's daily life and makes them unable to work and study normally. Traditional Chinese medicine (TCM) prescription Danggui Sini Decoction (DGSND) has been widely used in clinical practice and achieved good results. But there is no high-level evidence to support this result. The aim of this study is to evaluate DGSND's efficacy and safety in the management of KOA. METHODS: We will search 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to September 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. RESULTS: This study will compare the effects of DGSND and any other different methods on patients with KOA to provide high-quality, evidence-based clinical recommendations. CONCLUSION: The study provides a trustable clinical foundation for DGSND in the treatment of KOA.

Application of Physiologically Based Pharmacokinetic Modeling to Predict Maternal Pharmacokinetics and Fetal Exposure to Oxcarbazepine.

Pregnancy is associated with physiological changes that may affect drug pharmacokinetics (PKs). The aim of this study was to establish a maternal-fetal physiologically based pharmacokinetic (PBPK) model of oxcarbazepine (OXC) and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (MHD), to (1) assess differences in pregnancy, (2) predict changes in PK target parameters of these molecules following the current dosing regimen, (3) assess predicted concentrations of these molecules in the umbilical vein at delivery, and (4) compare different methods for estimating drug placental penetration. Predictions using the pregnancy PBPK model of OXC resulted in maternal concentrations within a 2-fold error, and extrapolation of the model to early-stage pregnancies indicated that changes in median PK parameters remained above target thresholds, requiring increased frequency of monitoring. The dosing simulation results suggested dose adjustment in the last two trimesters. We generally recommend that women administer ≥ 1.5× their baseline dose of OXC during their second and third trimesters. Test methods for predicting placental transfer showed varying performance, with the in vitro method showing the highest predictive accuracy. Exposure to MHD in maternal and fetal venous blood was similar. Overall, the above-mentioned models can enhance understanding of the maternal-fetal PK behavior of drugs, ultimately informing drug-treatment decisions for pregnant women and their fetuses.

Effects of postoperative adjuvant steroid therapy on the outcomes of biliary atresia: A systematic review and updated meta-analysis.

Background: Postoperative adjuvant steroid therapy is regarded as the conventional treatment for patients with biliary atresia (BA) who have undergone Kasai portoenterostomy (KP). However, whether the steroid therapy can improve BA outcomes is controversial. This meta-analysis aimed to evaluate the effects of adjuvant steroid therapy on the surgical prognosis of BA. Methods: We searched related studies published in PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database up to May 2022. Data on the effect of steroid use on the clinical prognosis of the patients, including the jaundice clearance rate (JCR), native liver survival rate (NLSR) at 6, 12, and 24 months after KP, and the incidence of cholangitis, were extracted. Subgroup analyses based on age at KP, administration method, initial dosage, and steroid type were conducted. Statistical analysis was conducted using Stata/SE 12.0. Results: Eleven articles (a total of 1,032 patients) were included in the present meta-analysis. The results demonstrated that postoperative adjuvant steroid therapy improved JCR at the 6/12/24-month follow-up (RR: 1.35, 95% CI: 1.18-1.55, p < 0.001; RR:1.49, 95% CI, 1.12-1.99, p = 0.006; RR: 1.41, 95% CI: 1.14-1.75, p = 0.002) and improved NLSR at the 24-month follow-up (RR: 1.31, 95% CI: 1.03-1.68, p = 0.028). However, steroids could not significantly improve NLSR at the 6/12-month follow-up (RR: 1.06; 95% CI: 0.98-1.15; p = 0.17; RR: 1.22; 95% CI: 0.97-1.54; p = 0.095), and might not decrease the incidence of postoperative cholangitis (RR: 0.78, 95% CI: 0.60-1.01, p = 0.058). Furthermore, subgroup analyses confirmed that three variables (age at KP, administration method, and initial dosage) could affect the efficacy of steroids in BA patients. Conclusion: Postoperative adjuvant steroid therapy can significantly improve bile flow. The superiority of steroid therapy was more remarkable in patients aged ≤70 days at KP than in those aged >70 days. Additionally, intravenous followed by oral steroid administration method and medium initial dosage seemed to have the more reliable efficiency on bile flow. And patients treated by steroid had better long-term (24-month) native liver survival, but there is no significant effect on short-term native liver survival and postoperative cholangitis. Further studies are warranted.