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.

ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

AIM To investigate the influencing factors in scale-up of extraction process for Yunpi Xiaoshi Prescription.METHODS HPLC was adopted in the content determination of catechin,ferulic acid,taxifolin,isovitexin,narirutin,atractylenolideⅡ,naringin,morin,hesperidin,luteolin,hederagenin,atractylenolideⅠ,naringenin and hesperetin,the fingerprints were established,after which the effects of container volume,optimal fire and feeding quantity on the contents of various constituents were evaluated.RESULTS Fifteen batches of samples demonstrated the similarities of more than 0.995.Fourteen constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 96.4%-103.3%with the RSDs of 0.5%-2.7%.The influencing degree of optimal fire was greater than that of container volume and feeding quantity.CONCLUSION The combination of multi-component content determination and fingerprints can provide data basis and theoretical reference for the technology of consistency evaluation in scale-up of extraction process for Yunpi Xiaoshi Prescription.

Objective To establish a rapid high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the determination of linezolid and vancomycin in trace plasma/serum from pediatric patients with severe infection.Methods The plasma/serum specimens(10 μL)were precipitated by methanol,then the supernatant was injected for detection directly.The internal standards were linezolid-D3 and norvancomycin.The chromatographic separation was performed with gradient elution on a Kinetex? EVO C18 column(30.0 mm × 2.1 mm,2.6 μm)using water and acetonitrile,each containing 0.1％formic acid,as mobile phase.The flow rate was 0.5 mL·min-1 and column temperature was 40 ℃.The injection volume was 2 μL and the total run time was 2 min.For mass spectrometry,electrospray ionization source was chosen,positive ion monitoring was used with multi-reaction monitoring(MRM)mode.The selectivity,lower limit of quantification(LLOQ)& calibration curve,accuracy & precision,recovery,matrix effect,stability,cross detection of plasma and serum samples,evaluation of hemolytic and hyperlipidemic effect were investigated.Results The retention times of linezolid,vancomycin,internal standard linezolid-D3 and norvancomycin were 1.18,1.03,1.17 and 1.01 min,respectively.The calibration curves of linezolid and vancomycin were y=8.95 × 10-1x+3.49 × 10-3(r=0.997 1)and y=3.13 × 10-1x+6.93 × 10-2(r=0.997 4),with the linear ranges of 0.2-25.6 μg·mL-1 and 1-128 μg·mL-1,and the lower limits of quantification were 0.2 μg·mL-1 and 1 μg·mL-1,respectively.The intra-run and inter-run precisions relative standard deviation(RSD)were both less than 9.55％.The average extraction recoveries of the two drugs were 96.24％-104.57％.The RSDs of internal standards-normalized matrix effect were no more than 7.58％.Plasma and serum matrix samples could be cross-detected.The maximum tolerable hemolysis degree of linezolid and vancomycin were 2％and 5％,respectively,and the hyperlipidemic effect did not affect the quantitation.The stability of the samples was good under test conditions.This method was successfully applied to the analysis of plasma samples from 28 pediatric patients with severe infection in our hospital.Conclusion This assay is sample-saving,simple,rapid,accurate and robust,widely used,which can be applied to combination medication studies of linezolid and vancomycin and their therapeutic drug monitoring in pediatric patients.

In the process of seeking new strategies to improve the efficacy of antidepressants,traditional Chinese medicine inter-vention has gradually revealed its unique prevention and treat-ment advantages.The dopamine reward system is closely in-volved in the pathological occurrence and development of depres-sion.Currently,research has mostly focused on the functional mechanism of a specific nucleus in the dopamine reward system,and there is less research focused on the functional mechanism of the neural circuit.In the current micro research on reward cir-cuits,the association between abnormal reward circuits and neg-ative emotions such as anxiety and depression has been widely recognized.Traditional Chinese medicine intervention can exert antidepressant effects by influencing reward circuits.This article provides a review on the loop mechanism of dopamine reward system involvement in depression and research on traditional Chinese medicine intervention.

AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P＜0.05);no significantly changed AI score(P＞0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P＜0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P＜0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.

Abstract: Objective　To analyze the laboratory indexes of patients infected with malaria patients and COVID-19, so as to provide reliable evidence for the diagnosis of mixed infection of both. Methods　The routine clinical laboratory items such as routine blood, biochemistry and lymphocyte subsets were tested in three cases of COVID-19 complicated with falciparum malaria who admitted to Guangzhou Eighth People's Hospital Affiliated to Guangzhou Medical University from July to December 2020 were tested. Laboratory data were stage-wise analyzed in conjunction with changes in the course of disease. Results　Three patients confirmed COVID-19 infection recruited all had malaria infection history. Fever, headache, and other symptoms emerged on the 4rd to 11th day after admission. Malaria parasite was detected by malaria parasite antigen testing and blood smear testing, and all three patients had re-ignition of malaria after being confirmed COVID-19 infection. In the early stage of malaria relapse, lymphocytes decreased, CRP and SAA increased, and gradually returned to normal level after antimalarial treatment. Interestingly, we only found one patient at the initial stage of malaria detection showed PLT decreased, no other unnormal changes in other routine blood results (WBC, ESO) and liver function results (ALT, AST, GGT, TBIL, DBIL, CG) were found from the beginning to end course of the disease. Conclusion　COVID-19 infection may promote the resurgence of malaria, so the relapse of malaria should be monitored especially for the patient with malaria infection history who begin to develop fever and other symptoms a few days after the diagnosis of COVID-19. The inflammatory indicators would be worth able as an auxiliary judgment basis for the effective treatment of the two combined infection.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Aim To explore the mechanism of process¬ing and increasing efficiency of Arisaematis rhizomz preparatum. Methods UPLC-Q-TOF-MS/MS tech¬nology was used to detect the chemical components be¬fore and after processing of Arisaematis rhizomz prepara¬tum, and its mechanism of action was analysed in the treatment of 44 asthma and phlegm " by using network pharmacology. A rat model of allergic asthma was es- tablished to compare the efficacy of Arisaematis rliizoma before and after processing. Results A total of 27 chemical components were identified, among which cur- cumin ,6-gingerol and other components increased after processing. Combined with the database prediction, the action mechanism of the 36 chemical components in the treatment of 44 asthma and phlegm" diseases was dis¬cussed and predicted through network pharmacology. The results of animal experiments showed that the effect of processed Arisaematis rhizoma on allergic asth¬ma was better than that of Arisaematis rhizoma, but there was no significant difference. Conclusions The addition of curcumin, 6-gingerol, camphor, demethyl- curcumin and other components after the processed Ari¬saematis rhizomz preparatum may be the reason for the synergistic effect of Arisaematis rhizomz preparatum in the treatment of allergic asthma.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.