This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans ; Apoptosis/drug effects* ; Hep G2 Cells ; Glycyrrhetinic Acid/pharmacology* ; Doxorubicin/pharmacology* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/physiopathology* ; Mitochondria/metabolism* ; Endoplasmic Reticulum/metabolism* ; Cell Survival/drug effects* ; Membrane Proteins/genetics*

Objective To observe the clinical efficacy of joint needling method combined with ultrasound in the treatment of qi stagnation and blood stasis type of patellofemoral pain syndrome(PFPS).Methods Eighty-six patients with qi stagnation and blood stasis type of PFPS were randomly divided into observation group and control group,with 43 cases in each group.The control group was given western medicine conventional treatment combined with functional exercise,and the observation group was given joint needling method combined with ultrasound treatment on the basis of the control group.Both groups were treated for 2 consecutive weeks.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of knee pain and the Kujala scale scores of the two groups were observed before and after treatment.The changes in active range of motion(AROM)of the affected knee joint were compared before and after treatment between the two groups.Results(1)After treatment,the VAS scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of VAS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the Kujala scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of Kujala scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the AROM of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of AROM,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 95.35%(41/43)in the observation group and 81.40%(35/43)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The joint needling method combined with ultrasound can significantly relieve the pain symptoms of patients with PFPS and promote the recovery of knee joint function,and the clinical efficacy is remarkable.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G₀/G₁ phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Flavonoids/pharmacology* ; Colonic Neoplasms/prevention & control* ; Animals ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Mice ; Mice, Inbred BALB C ; Cell Movement/drug effects* ; Humans ; Gene Expression Regulation, Neoplastic/drug effects* ; Cell Cycle Checkpoints/drug effects*

As a single-center retrospective study, we analyzed the results of rotavirus and human adenovirus antigens in stool samples with colloidal gold immunochromatography method in children with acute gastroenteritis under the age of five who were treated in our hospital from 2019 to 2022. After excluding nonconforming cases and duplicate cases, 2 896 cases were included, of which 559 cases were detected with at least one viral antigen. According to the test results, they were divided into RV positive group, HAdV positive group and RV & HAdV double positive group. The gender, age, seasonal distribution, clinical symptoms and related laboratory tests were compared and analyzed with χ² test, analysis of variance and nonparametric test. Among the single samples from 2 896 children, the positive rate of RV antigen was 6.21% (180/2 896), the positive rate of HAdV antigen was 10.91% (316/2 896), and the double positive rate of RV & HAdV was 2.18% (63/2 896). The positive rate of HAdV antigen in 2021 was 16.11%, a significant increase compared with 6.20% in 2020. RV infection has obvious seasonality, and spring and winter are the seasons with high incidence of infection (χ²=74.018, P<0.001), while HAdV infection has no obvious seasonality (χ²=2.110, P=0.550), showing sporadic infection throughout the year. The proportions of fever and vomiting symptoms in children with RV infection were significantly higher than those in the HAdV infection group (χ²=40.401, P<0.001; χ²=32.593, P<0.001), but the positive rate of white blood cells in the stool was significantly lower than that in the HAdV infection group (χ²=13.741,P<0.01). In summary, paying attention to the epidemiological changes of RV and HAdV is of great significance for clinical diagnosis and treatment and disease prevention and control.
Child ; Humans ; Infant ; Rotavirus ; Retrospective Studies ; Gastroenteritis/epidemiology* ; Hospitals ; Feces ; Adenoviruses, Human ; Adenovirus Infections, Human/epidemiology*

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.
Female ; Male ; Child ; Humans ; Child, Preschool ; Multiple Organ Failure ; Retrospective Studies ; Bronchitis/etiology* ; Dyspnea ; Pleural Effusion ; Pulmonary Atelectasis ; Plastics ; Respiratory Insufficiency

Objective:To investigate the clinical significance of protein disulfide isomerase A3 (PDI) A3 (PDIA3) expression in hepatocellular carcinoma tissues and its effect of PDIA3 on the expression of IL6 and IL17 in hepatocellular carcinoma cells.Methods:Immunohistochemistry was used to detect the expression of PDIA3 in the tissues of 72 patients with liver cancer and their adjacent tissues. HepG2 cells were divided into experimental group and control group. The cells in the experimental group were transfected with PDIA3-siRNA plasmid, and the cells in the control group were transfected with MOCK-siRNA plasmid. Fluorescence quantitative PCR was used to detect the content of PDIA3 mRNA in each group of cells. The expressions of PDIA3, IL6 and IL17 in each group of cells were detected by Western blot. The proliferation ability of each group of cells was detected by CCK8.Results:The positive rate of PDIA3 in liver cancer tissues was 85.22% (75/88), and the expression rate in adjacent tissues was 6.81% (6/88). The expression rate of PDIA3 in liver cancer tissues was significantly higher than that in adjacent tissues. The difference was statistically significant ( P<0.001). After transfection of siRNA, the expression levels of PDIA3 mRNA in HepG2 cells in the experimental group and control group were 1.23±0.20 and 0.43±0.12, respectively, and the expression levels of PDIA3 protein were 1.19±0.11 and 0.23±0.08, respectively. The expression levels of IL6 were 1.11±0.15 and 0.57±0.09, respectively. The expression levels of IL17 were 1.19±0.14 and 0.45±0.08, respectively, and the expressions of IL6 and IL17 were significantly decreased (all P<0.05). The absorbance of HepG2 cells in the experimental group and the control group at 120 h was 2.28±0.10 and 1.11±0.09, respectively, and the cell proliferation ability of the experimental group was significantly decreased ( P<0.05) . Conclusions:The expression of PDIA3 is significantly increased in hepatocellular carcinoma, which may be related to the malignancy of hepatocellular carcinoma. PDIA3 affects the proliferation of hepatocellular carcinoma cells by regulating the expression of IL6 and IL17.

ObjectiveThis study aimed to assess the circulating bilirubin profile ［total bilirubin （TBIL）， conjugated bilirubin （DBIL）， unconjugated bilirubin （IBIL）］ and their associations with nonproliferative diabetic retinopathy （NPDR）. MethodsA case-control study which enrolled 312 type 2 diabetic mellitus （T2DM） patients （78 newly diagnosed NPDR 1：3 matched with 234 T2DM without diabetic retinopathy） was conducted. Diabetic retinopathy was screened by artificial intelligence fundus camera and further confirmed by the ophthalmologist， and demographic and clinical information were collected. Serum bilirubin and related biochemical indicators were assessed. ResultsPatients with NPDR had significantly lower serum TBIL， DBIL and IBIL concentrations （P values were 0.003， 0.001 and 0.006）， which were not associated with glycated hemoglobin （HbA1c） concentration （all P values >0.05）. The association persisted after adjustment for traditional risk factors including gender， diabetes duration， HbA1c and systolic blood pressure. Moreover， low IBIL had a higher risk of NPDR with odds ratio （OR） 95%CI of 3.44 （1.04， 11.38） in well glycemic controlled T2DM patients （HbA1c ≤7%） or of 2.53 （1.10， 5.82） in T2DM patients without microalbuminuria ［urine albumin creatine ratio （UACR） ≤30mg/g］； low DBIL had a higher risk of NPDR with OR 95%CI of 2.05 （1.09， 3.86） in poor glycemic controlled T2DM patients （HbA1c>7%） or of 2.40 （1.14， 5.02） in T2DM patients with microalbuminuria （UACR >30mg/g）. ConclusionOur results suggested that circulating bilirubin level is inversely and independently associated with NPDR which might be an early clinical biomarker for predicting and preventing diabetic retinopathy.

Objective: To investigate the related factors associated with the structure of the gut microbial community in HIV infection/AIDS cases (HIV/AIDS) in Henan province. Methods: The convenience sampling method was used to select 122 cases who were receiving Antiviral Treatment (ART) or ART-naive in Henan. Whole blood and stool specimens were collected. Genomic DNA of stool samples was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq 6000 high-throughput sequencing system. The analysis was performed mainly at the genus level, and the 30 genera with the highest abundance were selected as a measure of the gut microbial community structure. The correlation between community structure and related factors was analyzed using redundancy analysis and Envfit function. Results: 122 cases were finally completed sequencing and analysis, the average BMI was (23.62±2.78) kg/m² and the average age was (47±13) years. Among them, male accounted for 66.39% (81/122), and heterosexual transmission route constituted the largest ratio, accounting for 51.64% (63/122). 36 cases were treatment naive (29.51%, 36/122). The top five dominant genera of the total population (122 cases) were Prevotella, Roseburia, Megamonas, Bacteroides and Faecalibacterium and the top five dominant genera of the ART population (86 cases) were Prevotella, Megamonas, Bacteroides, Roseburia and Faecalibacterium. The top five dominant genera of the ART-naive population (36 cases) appeared as Prevotella, Faecalibacterium, Roseburia, Bacteroides and Megamonas. In the total population, ART (P<0.001) was the most significant factors of community structure. Other significant factors were: duration of diagnosis (P=0.009), viral load (P=0.022) and anti-HCV (P=0.018). ART was positively correlated with Megamonas and negatively correlated with Prevotella, Roseburia and Faecalibacterium, while the other three factors of duration of diagnosis, viral load and anti-HCV were positively correlated with Prevotella, Roseburia and Faecalibacterium and negatively correlated with Megamonas. In the ART-naive population, duration of diagnosis (P=0.003) were the factors significantly associated with community structure. Duration of diagnosis was positively correlated with Roseburia, Faecalibacterium, Megamonas and Prevotella and negatively correlated with Bacteroides. Conclusion: ART and duration of diagnosis were factors significantly associated with gut microbial community structure and had a significant impact on multiple high-abundance genera.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adult ; Gastrointestinal Microbiome/genetics* ; HIV Infections/epidemiology* ; Humans ; Male ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics*