Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective:To explore the clinical effect of composite skin transplantation combined with systemic rehabilitation in the treatment of extensive scar contracture deformity around the popliteal fossa in children after burns.Methods:A retrospective observational research method was adopted. Seventeen children with extensive scar contracture deformities around the popliteal fossa after burns who met the inclusion criteria and were admitted to the First Affiliated Hospital of Air Force Military Medical University from March 2018 to April 2022 were selected. Among them, there were 10 males and 7 females, aged 2-11 years, with scar contracture deformities lasting from 10 months to 9 years, all located around the popliteal fossa, 10 cases of right popliteal fossa, 5 cases of left popliteal fossa, 2 cases of bilateral popliteal fossa, scars around the popliteal fossa result in a knee joint extension angle of only 95° to 115°. The scar contracture during surgery was thoroughly released, joint mobility was restored, so as to form a secondary wound range of 10 cm×8 cm-20 cm×13 cm. In stage Ⅰ, after completely releasing the scar contracture, the wound was covered with negative pressure closure drainage (VSD) for 2-3 days. In stage Ⅱ, a large autologous blade thick scalp and allogeneic decellularized dermal matrix composite graft was performed to repair the wound around the popliteal fossa. After 8-10 days of surgery, the dressing was changed to check the survival of the skin graft. One week after the skin graft survived, a 12 month orderly knee joint function training was conducted under the guidance of a rehabilitation therapist. Postoperative sequential treatment with a combination of strong pulsed light and ultra pulsed carbon dioxide lattice laser for 5-7 courses of significant scar hyperplasia in the skin graft area and edges.Results:15 cases of pediatric patients had good skin graft survival; One patient developed a wound due to partial displacement of the transplanted autologous scalp, and one patient developed a plasma swelling under the limb graft, which was drained through an opening. Two patients underwent dressing changes for 3 weeks before the wound healed. After follow-up for 6 to 36 months, the elasticity and appearance of the skin graft were similar to those of a medium thickness skin graft. Children with knee joint contracture were able to fully extend to 180°, and knee joint function was significantly improved. There was no scar formation or hair loss in the donor skin area.Conclusions:The combination of composite skin transplantation and systematic rehabilitation has a good effect on the treatment of extensive scar contracture around the popliteal fossa in children after burns, avoiding the problem of scars left in the donor area due to autologous skin grafting.

As a potent narcotic opioid analgesic,fentanyl has been used as intravenous anesthesia for clinical procedures while also being abused by drug users,resulting in an increasing number of deaths year by year,and thus it is urgent to develop rapid screening methods for fentanyl.In this study,by using a binary metal-organic framework MIL-88B(Fe/Ni)as an electrocatalyst,an electrochemical sensor based on multi-walled carbon nanotubes(MWCNTs)modified glassy carbon electrode(GCE)was constructed for rapid detection of fentanyl.The morphology,crystal structure and elemental characteristics of the synthesized MIL-88B(Fe/Ni)/MWCNTs and MIL-88B(Fe/Ni)composites were confirmed by scanning electron microscopy(SEM),energy dispersive X-ray spectroscopy(EDS),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS).In addition,the electrochemical characterization also revealed that the synthesized MIL-88B(Fe/Ni)/MWCNTs composites modified GCE possessed low electrochemical impedance and large electrochemical surface area with ultra-high sensitivity to fentanyl.The experimental conditions for the electrochemical detection of fentanyl were optimized and the limit of detection(LOD,3Sb/M)for fentanyl was 0.015 μmol/L with a linear range of 0.04-10 μmol/L,and the reproducibility,selectivity and stability were all favorable.In addition,the developed sensor showed satisfactory performance in real samples,with recoveries ranging from 58.6%to 81.5%and from 82.7%to 97.5%in urine and blood,respectively,at concentration levels of 0.2-1.0 μmol/L.The proposed MIL-88B(Fe/Ni)/MWCNTs composite could be used as a novel electrode material for electrochemical detection of fentanyl,and had great potential for rapid detection of fentanyl in public security anti-drug or medical emergency.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To study the effects of different doses of vancomycin bone cement on serum inflammatory factors and joint function in patients undergoing total knee arthroplasty.Methods A total of 128 patients who underwent total knee arthroplasty admitted to Handan First Hospital from August 2021 to January 2023 were selected as the study subjects.They were divided into group A(acrylic bone cement without vancomycin),group B(0.5 g vancomycin per 40 g acrylic bone cement),group C(1.0 g vancomycin per 40 g acrylic bone cement)and group D(2.0 g vancomycin per 40 g acrylic bone cement)by random number table method,with 32 patients in each group.High performance liquid chromatography was used to detect the concentration of vancomycin in drainage fluid at different time points after operation of patients in group B,group C,and group D.Immune scattering turbidimetry and Westergren method were used to detect the levels of serum C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)of patients in the four groups before operation,7 days and 6 months after operation.Hospital for special surgery knee score(HSS)was used to evaluate the knee joint function of patients in the four groups before operation and 6 months after operation.Results The concentration of vancomycin in drainage fluid of patients in group B,group C,and group D increased with the increase of dose(P<0.05),and decreased with the extension of time(P<0.05).The postoperative serum CRP and ESR levels in the four groups increasing first and then decreased with time(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group B,group C,and group D were significantly lower than those in group A(P<0.05).The levels of serum CRP and ESR 7 days and 6 months after operation of patients in group C and group D were significantly lower than those in group B(P<0.05),while there was no significant difference in serum CRP and ESR levels between group C and group D(P>0.05).The HSS scores 6 months after operation of patients in the four groups obviously improved(P<0.05);the HSS scores 6 months after operation of patients in group B,group C and group D were higher than those in group A(P<0.05);the HSS scores 6 months after operation of patients in group C and group D were obviously higher than those in group B(P<0.05),while there was no obvious difference in the HSS scores 6 months after operation between group C and group D(P>0.05).Conclusion The use of bone cement containing vancomycin can obviously reduce the levels of serum inflammatory factors CRP and ESR in patients undergoing total knee arthroplasty,prevent postoperative infection,and improve joint function of patients.The degree of action of different doses of vancomycin also varies,and it is recommended to use 1.0 g of vancomycin in clinical practice.