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1.
Discov Med ; 36(187): 1672-1677, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39190382

ABSTRACT

BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage. METHODS: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities. RESULTS: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors. CONCLUSIONS: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.


Subject(s)
Evoked Potentials, Auditory, Brain Stem , Hyperbilirubinemia, Neonatal , Humans , Female , Infant, Newborn , Male , Retrospective Studies , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/physiopathology , Hyperbilirubinemia, Neonatal/complications , Hyperbilirubinemia, Neonatal/diagnosis , Risk Factors , Bilirubin/blood , Pregnancy , Diabetes, Gestational/physiopathology , Diabetes, Gestational/blood
2.
bioRxiv ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39026854

ABSTRACT

Brown adipose tissue (BAT) is mammals' primary non-shivering thermogenesis organ, and the molecular mechanisms regulating BAT growth and adipogenesis are largely unknown. The Hippo-YAP pathway has been well-known for controlling organ size, and Vestigial like 4 (VGLL4) is a transcriptional regulator that modulates the Hippo-YAP pathway by competing against YAP for binding to TEAD proteins. In this study, we dissected the function of VGLL4 in regulating BAT development. We generated a conventional Vgll4 mutant mouse line, in which the two Tondu (TDU) domains of VGLL4 were disrupted. We found that deletion of the TDU domains of VGLL4 resulted in perinatal lethality and paucity of the interscapular BAT. Histological and magnetic resonance imaging studies confirmed that the adipogenesis of BAT was impaired in Vgll4 mutants. Adeno-associated virus (AAV) mediated, brown adipocyte-specific overexpression of VGLL4 increased BAT volume and protected the adult male mice from acute cold stress. Genomic studies suggest that VGLL4/TEAD1 complex directly regulates the myogenic and adipogenic gene expression programs of BAT. In conclusion, our data identify VGLL4 as a previously unrecognized adipogenesis factor that regulates classical BAT development.

3.
Article in English | MEDLINE | ID: mdl-39074565

ABSTRACT

PURPOSE: To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiotherapy (PBMS-IMRT) in reducing bone density loss for patients with cervical cancer undergoing pelvic radiotherapy (RT). METHODS AND MATERIALS: Non-surgical cervical cancer patients with Stage Ib2-IIIc cancer were randomly allocated into the PBMS group or the control group. The PBMS group additionally received PBM dose constraint. Computed tomography (CT) imaging sets were acquired at baseline and at 1, 3, 6, 9, and 12 months after treatment. Radiation dose and Hounsfield unit (HU) were registered. Bone density loss rates and fracture events at different follow-up time points were recorded. RESULTS: Data from 90 patients in the PBMS group and 86 patients in the control group were used for statistical analysis, which included 30 and 26 patients with extended-field RT (EFR), respectively. The median follow-up for all patients was 12 months. Compared to baseline, the bone density of all bones at the last follow-up had decreased by 43% and 53% in the PBMS and control groups, respectively, with the most significant decline at 1 month after treatment. Although patients without extended-field radiation received minimal irradiation in the upper lumbar spine, a 22.33% decrease in bone density was detected. In the group of patients with EFR, the decrease was 51.18% (P < 0.01). Lumbar or pelvic fracture incidence rates of patients in the PBMS and control groups were 7.8% and 12.79%, respectively. Among the dosimetric parameters, mean dose had the strongest correlation with bone density loss. CONCLUSION: In patients undergoing pelvic RT, the loss of bone density can begin to appear early after RT, and it can occur either inside or outside of the irradiation field. Results of this study showed that PBMS-IMRT reduced bone mineral density loss compared with IMRT alone.

4.
J Med Virol ; 96(6): e29762, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923563

ABSTRACT

Functional cure of hepatitis B virus (HBV) is an optimal treatment goal for chronic hepatitis B, with the loss of hepatitis B surface antigen (HBsAg) being a crucial indicator. However, the adequacy of HBsAg loss for evaluating functional cure of HBV in patients co-infected with HBV/human immunodeficiency virus (HIV) remains controversial. In this study, we measured HBV pregenomic RNA (pgRNA), a potential biomarker that correlates with covalently closed circular DNA, in the frozen plasma of 98 patients with HBsAg loss from a large HIV/HBV co-infection cohort in Guangzhou, China. HBV pgRNA was still detected in 43.9% (44/98) of the patients, suggesting active HBV replication in individuals with HBsAg loss. Our observations imply that HBsAg loss may not be a reliable predictor of HBV functional cure in cases of HIV/HBV co-infection.


Subject(s)
Biomarkers , Coinfection , HIV Infections , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B, Chronic , RNA, Viral , Humans , HIV Infections/virology , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B Surface Antigens/blood , Coinfection/virology , Male , Hepatitis B virus/genetics , Female , Adult , RNA, Viral/blood , RNA, Viral/genetics , Biomarkers/blood , Middle Aged , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/complications , China , DNA, Viral/blood , Virus Replication , Cohort Studies , RNA
5.
PLoS One ; 19(4): e0301703, 2024.
Article in English | MEDLINE | ID: mdl-38574094

ABSTRACT

BACKGROUND AND OBJECTIVES: The potential association between rosacea and a heightened prevalence of Helicobacter pylori (HP) infection has been previously suggested. However, existing studies offer inconsistent results. This systematic review and meta-analysis aimed to elucidate the relationship between rosacea and HP infection. METHODS: We conducted comprehensive searches of PubMed, Embase, and Web of Science databases to identify relevant observational studies for our investigation. We utilized the random-effects model to aggregate the data to address the potential influence of heterogeneity among the studies on the outcome. RESULTS: Our analysis incorporated twenty-five datasets from 23 case-control and cross-sectional studies, encompassing 51,054 rosacea patients and 4,709,074 controls without skin disease. The pooled results revealed a significantly higher prevalence of HP infection in individuals with rosacea compared to controls (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.17-1.95, p<0.001; I2 = 79%). Subgroup analysis indicated an increased prevalence of HP infection in rosacea studies that utilized one (OR: 1.72, 95% CI: 1.11-2.66, p = 0.02; I2 = 76%) or more tests for HP infection (OR: 2.26, 95% CI: 1.29-3.98, p = 0.005; I2 = 56%). However, this association was not observed in population-based studies that determined HP infection based on prescription records for HP eradication drugs (OR: 0.90, 95% CI: 0.76-1.07, p = 0.024; I2 = 54%). CONCLUSION: Rosacea may be significantly associated with a higher prevalence of HP infection. High-quality prospective studies with delicately controlled confounding factors are needed to determine if HP infection is a risk factor for rosacea.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Rosacea , Rosacea/microbiology , Rosacea/epidemiology , Rosacea/complications , Humans , Helicobacter Infections/complications , Helicobacter Infections/epidemiology , Prevalence , Case-Control Studies , Odds Ratio , Cross-Sectional Studies
7.
iScience ; 27(2): 109019, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38352222

ABSTRACT

Dexamethasone is commonly used as an adjuvant to prolong peripheral nerve block analgesia, but the optimal timing is unclear. This randomized equivalence trial tested whether preoperative versus postoperative intravenous dexamethasone have equivalent analgesic effects when combined with interscalene brachial plexus block for shoulder surgery. 168 patients were randomized to receive 5 mg dexamethasone either preoperatively or postoperatively. The primary outcome was duration of analgesia, analyzed for equivalence with a 2-h margin. The mean durations were equivalent between groups (11.5 h preoperative versus 10.7 h postoperative). The confidence intervals fell within the equivalence margin. There were no other clinically significant differences in secondary outcomes like time to first analgesia, motor recovery, opioid consumption, blood glucose, or complications. In conclusion, as an adjuvant for nerve block, preoperative and postoperative intravenous dexamethasone provide equivalent analgesic duration, allowing for flexibility in clinical use. This addresses previous uncertainty about timing while demonstrating equivalent efficacy.

8.
Bioinformatics ; 40(1)2024 01 02.
Article in English | MEDLINE | ID: mdl-38216534

ABSTRACT

MOTIVATION: Transcription factor binding sites (TFBS) are regulatory elements that have significant impact on transcription regulation and cell fate determination. Canonical motifs, biological experiments, and computational methods have made it possible to discover TFBS. However, most existing in silico TFBS prediction models are solely DNA-based, and are trained and utilized within the same biosample, which fail to infer TFBS in experimentally unexplored biosamples. RESULTS: Here, we propose TFBS prediction by modified TransFormer (TFTF), a multimodal deep language architecture which integrates multiomics information in epigenetic studies. In comparison to existing computational techniques, TFTF has state-of-the-art accuracy, and is also the first approach to accurately perform genome-wide detection for cell-type and species-specific TFBS in experimentally unexplored biosamples. Compared to peak calling methods, TFTF consistently discovers true TFBS in threshold tuning-free way, with higher recalled rates. The underlying mechanism of TFTF reveals greater attention to the targeted TF's motif region in TFBS, and general attention to the entire peak region in non-TFBS. TFTF can benefit from the integration of broader and more diverse data for improvement and can be applied to multiple epigenetic scenarios. AVAILABILITY AND IMPLEMENTATION: We provide a web server (https://tftf.ibreed.cn/) for users to utilize TFTF model. Users can train TFTF model and discover TFBS with their own data.


Subject(s)
Genome , Multiomics , Binding Sites , Protein Binding , Transcription Factors/metabolism , Computational Biology/methods
9.
Int J Antimicrob Agents ; 63(3): 107080, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38163551

ABSTRACT

OBJECTIVE: To explore the effect of three-dimensional (3D) printing to create personalized antibiotic-loaded bone cement (ALBC) spacers to assist in treatment of periprosthetic infection after total hip arthroplasty (THA). METHODS: The data of 40 patients with postoperative infection after THA were analysed retrospectively. The patients were divided into two groups: the 3D-printing group (age 47-78 years, n = 20) and the conventional group (age 57-78 years, n = 20). In stage I surgery, 3D-printed silicone moulds were used to create ALBC spacers for the 3D-printing group, while traditional manual methods were used to create spacers for the conventional group. After the infection was controlled, both groups underwent conventional hip revision surgery (stage II surgery). All patients were evaluated using the Harris Hip Score (HHS) (primary outcome) for hip function. RESULTS: All 40 patients had follow-up data from 3 months after stage I surgery and 12 months after stage II surgery. The intergroup difference in HHS was 11.25 points [97.5% confidence interval (CI) 7.92-14.58; P < 0.01] at 3 months after stage I surgery, and 9.15 points (97.5% CI 4.82-13.48; P < 0.01) at 12 months after stage II surgery. The overall difference between the two groups was 9.55 points (97.5% CI 5.83-13.27; P < 0.01), which was significant (P < 0.05). CONCLUSION: During the follow-up period, the hip function of the 3D-printing group was superior to that of the conventional group following the treatment of infections after THA.


Subject(s)
Arthroplasty , Bone Cements , Humans , Middle Aged , Aged , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Printing, Three-Dimensional
10.
Cell Oncol (Dordr) ; 47(1): 157-174, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37632669

ABSTRACT

PURPOSE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. CONCLUSION: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.


Subject(s)
Ovarian Neoplasms , Oxidative Phosphorylation , Female , Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Up-Regulation
11.
Article in English | MEDLINE | ID: mdl-38082923

ABSTRACT

Grip strength measurement is one of the most accessible methods for measuring overall muscle strength, and many studies have shown a link between low grip strength and future diseases. In recent years, devices for grip strength measurements that can connect to digital devices for automatic data recording have been developed. However, such devices have high development costs and require daily maintenance. Therefore, this we propose a grip strength measurement method using the capacitance sensor of a smartphone and no electronic parts on the measurement device side.


Subject(s)
Hand Strength , Hand , Muscle Strength Dynamometer , Hand Strength/physiology , Costs and Cost Analysis , Electric Capacitance
12.
ACS Appl Mater Interfaces ; 15(51): 59643-59654, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38090754

ABSTRACT

The development of efficient blue thermally activated delayed fluorescence (TADF) emitters with an aggregation-induced emission (AIE) nature, for the construction of organic light-emitting diodes (OLEDs), is still insufficient. This can be attributed to the challenges encountered in molecular design, including the inherent trade-off between radiative decay and reverse intersystem crossing (RISC), as well as small singlet-triplet energy splitting (ΔEST) and the requirement for high photoluminescence quantum yields (ΦPL). Herein, we present the design of three highly efficient blue TADF molecules with AIE characteristics by combining π-extended donors with different acceptors to modulate the differences in the electron-donating and electron-withdrawing abilities. This approach not only ensures high emission efficiency by suppressing close π-π stacking, weakening nonradiative relaxation, and enhancing radiative transition but also maintains the equilibrium ratio between the triplet and singlet excitons by facilitating the process of RISC. These emitters exhibit AIE and TADF properties, featuring quick radiative rates and low nonradiative rates. The ΦPL of these emitters reached an impressive 88%. Based on their excellent comprehensive performance, nondoped PICzPMO and PICzPMO OLEDs achieved excellent electroluminescence performance, exhibiting maximum external quantum efficiency (EQEmax) of up to 19.5%, while the doped device achieved a higher EQEmax of 20.8%. This work demonstrated that by fusing π-extended large rigid donors with different acceptors, it is possible to regulate the difference in electron-donating and electron-withdrawing abilities, resulting in a small ΔEST, high ΦPL, and fast RISC process, which is a highly feasible strategy for designing efficient TADF molecules.

13.
Chin Med J (Engl) ; 136(22): 2686-2693, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37881959

ABSTRACT

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS: Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.


Subject(s)
Coinfection , HIV Infections , Hepatitis B, Chronic , Male , Humans , Adult , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , HIV Infections/drug therapy , HIV , DNA, Viral , Incidence , Coinfection/drug therapy , Retrospective Studies , Tenofovir/therapeutic use , Lamivudine/therapeutic use , Hepatitis B, Chronic/drug therapy
14.
Adv Sci (Weinh) ; 10(31): e2302417, 2023 11.
Article in English | MEDLINE | ID: mdl-37749873

ABSTRACT

Prokaryotic genomes are generally organized in haploid. In synthetic biological research, efficient chassis cells must be constructed to produce bio-based products. Here, the essential division of the ftsZ gene to create functional polyploid E. coli is regulated. The artificial polyploid E. coli containing 2-4 chromosomes is confirmed through PCR amplification, terminator localization, and flow cytometry. The polyploid E. coli exhibits a larger cell size, and its low pH tolerance and acetate resistance are stronger than those of haploid E. coli. Transcriptome analysis shows that the genes of the cell's main functional pathways are significantly upregulated in the polyploid E. coli. These advantages of the polyploid E. coli results in the highest reported L-threonine yield (160.3 g L-1 ) in fed-batch fermentation to date. In summary, an easy and convenient method for constructing polyploid E. coli and demonstrated its application in L-threonine production is developed. This work provides a new approach for creating an excellent host strain for biochemical production and studying the evolution of prokaryotes and their chromosome functions.


Subject(s)
Escherichia coli , Metabolic Engineering , Escherichia coli/genetics , Escherichia coli/metabolism , Metabolic Engineering/methods , Threonine/genetics , Threonine/metabolism , Fermentation
15.
Ann Med ; 55(2): 2249936, 2023.
Article in English | MEDLINE | ID: mdl-37683195

ABSTRACT

Objective: To investigate the effect of different bladder filling states on positioning errors in radiotherapy for cervical cancer and obtain the reference range of bladder filling consistency during radiotherapy.Methods: Patients who underwent postoperative radiotherapy for cervical cancer in Nantong Tumor Hospital from October 2018 to December 2019 were selected. According to the bladder filling deviation, they were divided into group A1 (deviation < 20%) and group B1 (deviation ≥ 20%). The bladder filling variations of the two groups were compared with different positioning errors. Group A2 has a positioning error of <0.4 cm, and group B2 has a positioning error of ≥0.4 cm. The reference range of bladder filling consistency during radiotherapy is obtained by analyzing the composition ratio of different positioning errors of bladder filling deviation.Results: This study included 195 patients with cervical cancer. The error of longitudinal and vertical position in group B1 was significantly higher than that in group A1 (0.50 ± 0.34 vs. 0.26 ± 0.22 cm, p < 0.001, and 0.22 ± 0.17 vs. 0.16 ± 0.12 cm, p < 0.001). Compared with group B2, the absolute deviation of bladder filling in group A2 (54.1% ± 54.4% vs. 25.6% ± 22.7%, p < 0.001) was slight. The chi-square test showed significant differences in the proportion of the positioning state of different bladder filling forms (χ2 = 31.006, p < 0.001). In addition, there was a significant difference in the proportion of stability errors in patients with poor stability in different directions (χ2 = 118.551, p < 0.001).Conclusion: In patients with cervical cancer fixed in the supine position, a bladder capacity deviation <20% is easier to achieve excellent positioning with, and it can better control the positioning error of radiotherapy and ensure the positioning accuracy of dose distribution to the target area. It can also achieve good tumor treatment effects. This range can be used as a reference for bladder filling consistency in patients with cervical cancer undergoing radiotherapy.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Urinary Bladder/surgery , Hysterectomy , Reference Values
16.
Br J Clin Pharmacol ; 89(12): 3659-3668, 2023 12.
Article in English | MEDLINE | ID: mdl-37464978

ABSTRACT

AIMS: This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates. METHODS: We performed a single-centre, open-label, three-period drug-drug interaction (DDI) study in 24 healthy subjects (NCT05392127). Subjects received a single oral dose of 5 mg warfarin (CYP2C9), 20 mg omeprazole (CYP2C19) and 15 mg midazolam (CYP3A4) on Days 1, 8 and 22, and received 0.5 mg repaglinide (CYP2C8) on Days 7, 14 and 28. Multiple oral doses of 8 mg SHR0302 were administered once daily from Day 8 to Day 28. RESULTS: The exposure of S-warfarin and repaglinide were comparable before and after SHR0302 administration. AUC of midazolam was not affected by SHR0302, whereas the administration of SHR0302 slightly decreased the Cmax of midazolam by 7.6% (single dose) and 15.7% (once daily for 14 days). The AUC0-t , AUC0-inf , and Cmax of omeprazole were slightly decreased after a single dose of SHR0302 by 19.2%, 21.8% and 23.5%, respectively. In the presence of SHR0302 for 14 days, the AUC0-t , AUC0-inf , and Cmax of omeprazole were marginally reduced by 3.0%, 16.4% and 8.3%, respectively. According to the induction mechanism of the CYP enzyme, for the investigation of the induction effect, the results of multiple administrations of the perpetrator were more reliable than those of the single dose. CONCLUSIONS: The results demonstrated that co-administration of SHR0302 8 mg once daily is unlikely to have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.


Subject(s)
Cytochrome P-450 CYP3A , Midazolam , Humans , Cytochrome P-450 CYP3A/metabolism , Midazolam/pharmacokinetics , Cytochrome P-450 CYP2C8/metabolism , Cytochrome P-450 CYP2C9 , Warfarin , Cytochrome P-450 CYP2C19/genetics , Drug Interactions , Cytochrome P-450 Enzyme System/metabolism , Omeprazole/pharmacokinetics , Healthy Volunteers
17.
Commun Biol ; 6(1): 515, 2023 05 13.
Article in English | MEDLINE | ID: mdl-37179427

ABSTRACT

Synthetic oscillators have become a research hotspot because of their complexity and importance. The construction and stable operation of oscillators in large-scale environments are important and challenging. Here, we introduce a synthetic population-level oscillator in Escherichia coli that operates stably during continuous culture in non-microfluidic environments without the addition of inducers or frequent dilution. Specifically, quorum-sensing components and protease regulating elements are employed, which form delayed negative feedback to trigger oscillation and accomplish the reset of signals through transcriptional and post-translational regulation. We test the circuit in devices with 1 mL, 50 mL, 400 mL of medium, and demonstrate that the circuit could maintain stable population-level oscillations. Finally, we explore potential applications of the circuit in regulating cellular morphology and metabolism. Our work contributes to the design and testing of synthetic biological clocks that function in large populations.


Subject(s)
Biological Clocks , Escherichia coli Proteins , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Feedback , Feedback, Physiological
18.
JMIR Res Protoc ; 12: e46054, 2023 May 29.
Article in English | MEDLINE | ID: mdl-37247222

ABSTRACT

BACKGROUND: Clinical rehabilitation for brachial plexus injury is difficult in terms of chronic pain and dysfunction. Physiotherapy is considered a routine intervention for rehabilitation. Common physical therapy may require a variety of instruments. One approach that does not need instruments, but belongs to the field of complementary and alternative medicine, is naprapathy. Naprapathy, also called Tuina in China, has been applied in rehabilitation after brachial plexus injury for a long time. Naprapathy can relieve chronic neuropathic pain, promote local blood circulation, and improve body edema. Naprapathy can passively help improve motor functions in patients with peripheral nerve injury. However, the efficacy of naprapathy in improving rehabilitation after brachial plexus injury is unclear. OBJECTIVE: This study aims to evaluate the additional value of naprapathy when combined with conventional physical therapy for the treatment of brachial plexus injury. METHODS: This will be a single-center randomized controlled trial. A total of 116 eligible patients with brachial plexus injury will be randomly divided into an experimental group (naprapathy plus physical therapy group) or a control group (physical therapy group). The participants will be followed up for 4 weeks of treatment. Observation outcomes will include the visual analog scale score, upper limb index, electromyography findings, and adverse reactions, among others. The measuring points for outcomes will be the baseline and the completion of treatment. In addition, a quality control group independent from the research team will be set up to control the quality of the trial. Finally, the data will be analyzed using SPSS software (version 21.0; IBM Corp). RESULTS: The study is recruiting participants. The first participant was enrolled in September 2021. As of January 2023, a total of 100 participants have been enrolled. The trial is expected to be completed by September 2023. The study protocol was approved by the Ethics Review Committee of Yue Yang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine (2021-012). CONCLUSIONS: One limitation of this trial is that we will be unable to achieve strict double-blinding because of the features of naprapathy. The trial aims to contribute reliable evidence for decision-making in naprapathy for treating brachial plexus injury. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043515; http://www.chictr.org.cn/showproj.aspx?proj=122154. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46054.

20.
Heliyon ; 9(4): e14962, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37025799

ABSTRACT

Background: We describe a case of severe cardiac insufficiency in an older adult undergoing open complex inguinal hernia repair. We present paravertebral injection technique at lower vertebral level without additional needle entry. The feasibility of this technique was verified by observing its intraoperative and postoperative analgesic effects. Case presentation: A 91-year-old male patient was admitted to the hospital with a very large mass in the right lower abdomen. Diagnostic ultrasonography revealed right inguinal irreducible hernia. The patient had severe cardiac insufficiency with a high risk of general and spinal anaesthesia. After adequate preoperative evaluation and cardiac therapy, the anesthesiologist determined to perform paravertebral block at T11 level using 20 mL of ropivacaine (0.5%) as a single anaesthetic technique to complete the operation. The surgery went uneventfully without using any auxiliary analgesics or sedative drugs. The first reported pain was 19 h after surgery. On the 11-point numeric rating scale, the highest and lowest pain scores within the first 24 h were 3 and 0, respectively. On postoperative day three, the patient was discharged and recovered without complications in 7 days and underwent one-month follow-up. Conclusions: Single paravertebral block at T11 level with 20 mL of ropivacaine (0.5%) may be an effective intraoperative anaesthetic technique in older adults with severe cardiac decompensation undergoing complex open inguinal hernia repair. The advantage of this technique was that the ipsilateral somatic and sympathetic nerves above and below the injection site could be blocked without additional needle insertion.

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