This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Hydrogen sulfide(H2 S),an endogenous gas trans-mitter involved in the regulation of vascular tone,has a variety of physiological properties,such as antihypertensive,vascular re-laxation,anti-inflammatory and antioxidant potential,and plays an important role in cardiovascular regulation.Chinese scholars call essential hypertension combined with hyperhomocysteinemia(HCY≥10 μmol·L-1)as H-type hypertension.Studies have shown that H2S can antagonized hypertension and hyperhomocys-teinemia,suggesting that H2S may be a potential therapeutic tar-get for H-type hypertension.Therefore,this article briefly sum-marizes the mechanism of H2S on hypertension and homocys-teine.Homocysteine(HCY)is closely related to the occurrence and development of cardiovascular diseases.Hyperhomocysteine-mia(HCY ≥ 10 μmol·L-1)is a risk factor for coronary ath-erosclerotic heart disease,stroke,and other cardiovascular dis-eases,and Chinese scholars define primary hypertension accom-panied by hyperhomocysteinemia as H-type hypertension,which accounts for about 75％of the adult hypertensive patients in Chi-na.The treatment of H-type hypertension should simultaneously reduce blood pressure and plasma HCY levels.Studies have shown that hydrogen sulfide(H2 S)can antagonise hypertension and high HCY,suggesting that H2S may be a potential therapeu-tic target for H-type hypertension.Therefore,this paper summa-rizes the mechanism of action of H2S on hypertension and HCY.

Objective To analyze the disease burden and change trend of breast cancer mortality among Chinese women from 2013 to 2021.Methods The indicators of breast cancer-related mortality (MR),age-standardized mortality rate (ASMR),deaths,and urban-rural deaths in the Chinese Cause of Death Surveil-lance Dataset from 2013 to 2021 were collected and collated,and the trend changes of MR,ASMR,and years lost in life of premature death (YLL) were analyzed,annual percentage change (APC) was used for trend a-nalysis,and Fisher substitution test was used to compare APC in different regions.Results From 2013 to 2021,a total of 88112 cases of breast cancer died,with an average annual MR of 7.56/100000 and an ASMR of 6.34/100000.From 2013 to 2021,the MR rate of breast cancer (APC=2.12%,t=5.414,P<0.001),MR in rural areas (APC=2.84%,t=7.581,P<0.001),and YLL in rural areas (APC=1.61%,t=3.588,P=0.009) showed an upward trend in China.MR at 40-<45 years old showed a downward trend (APC=-2.76%,t=-4.689,P=0.002),and at 70-<75 years old (APC=1.41%,t=2.494,P=0.041),75-<80 years old (APC=3.05%,t=3.690,P=0.008),and 80-<85 years old (APC=1.82%,t=2.909,P=0.023).There was a statistically significant difference in APC between MR and ASMR in urban and rural areas (P<0.001).There was no significant difference in the trend of other indicators (P>0.05).Conclusion From 2013 to 2021,the disease burden of breast cancer mortality in Chinese women showed an upward trend,and the comprehensive prevention and treatment of breast cancer should be strengthened to reduce the risk of breast cancer death.

By using thioflavin T(ThT)as displacement-based fluorescent probes,three kinds of aptasensors were constructed for rapid detection of three kinds of small molecules such as ochratoxin A(OTA),aflatoxin B1(AFB1)and adenosine.In the absence of target molecule,ThT bound with the aptamer to form an aptamer-ThT complex and exhibited a significant fluorescence response.Upon the addition of target molecule,because of the higher affinity between target and aptamer than that between ThT and the aptamer,ThT was displaced by the target molecule from the aptamer-ThT complex,resulting in weakened fluorescence signal.Based on this principle,the target molecule could be detected quantitatively.Further study through circular dichroism spectra showed that there was no significant change in the conformation of the aptamer after addition of ThT or target molecules.The stoichiometric ratios of ThT to OTAapt,AFB1apt and Adeapt measured through the method of equimolar continuous variation was 1∶1,1∶1 and 2∶1,respectively,and their dissociation constants were all larger than those between the target molecule and its aptamer.Therefore,the principle of this detection method was the displacement of fluorescent probe(ThT)in aptamer-ThT complex by target molecule,resulting in decrease of fluorescence intensity.Under optimal experimental conditions,the limits of detection(LODs)were 0.8 nmol/L for OTA,1.3 nmol/L for AFB1,and 0.10 μmol/L for adenosine,respectively.This method was label-free,simple to operate,with low cost,good selectivity and high sensitivity.The developed assay kit based on this method could be used for actual sample detection.