OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

Objective:To investigate the effect of flow cytometric minimal residual disease(MRD)detection at different time points during AML chemotherapy on prognosis.Methods:130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed,MRD was detected by flow cytometry,Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis,and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis.Cumulative incidence rate(CIR)analysis with competing risk model and variance analysis using Fine-Gray.Results:There were 81 CR1,26 CR2,14 PR,and 9 NR patients in 130 patients.OS of the CR1 group was higher than that in the CR2,PR,and NR groups.OS of the CR2 group was higher than that in the PR group,but there was no statistically difference compared to the NR group.There was no statistically difference in OS between the PR and NR groups.107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry,and after the first induction chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 65.3％and 27.9％respectively,the 4-year expected OS rates were 58.7％and41.4％respectively,and the 4-year expected CIR were 34.7％and 69.7％respectively,with statistically significant differences between 2 groups(x2=6.639,P=0.010;x2=6.131,P=0.013 and x2=6.637,P=0.010).After the second chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 50.8％and 37.9％respectively,the 4-year expected OS rates were 49.2％and 44.5％respectively,and the 4-year expected CIR were 49.2％and 59.5％respectively,with no statistically significant differences between 2 groups(x2=1.475,P=0.225;x2=2.432,P=0.119 and x2=1.416,P=0.234).During consolidation therapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 51.9％and 29.6％respectively,the 4-year expected OS rates were 67.5％and 24.6％respectively,and the 4-year expected CIR were 48.1％and 70.4％respectively,with statistically significant differences between 2 groups(x2=20.982,P＜0.001;x2=17.794,P＜0.001 and x2=19.879,P＜0.001).For patients with MRD-at all three time points and positive at either time point,the 4-year expected RFS rates were 69.9％and 33.3％respectively,the 4-year expected OS rates were 59.1％and 44.7％respectively,and the 4-year expected CIR were 30.1％and 65.1％respectively,with statistically significant differences between 2 groups(x2=7.367,P=0.007;x2=6.042,P=0.014 and x2=7.662,P=0.006).Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients'RFS and OS,while 2 cycles of induction chemotherapy achieved CR,MRD-after the first induction chemotherapy and MRD-after the second induction chemotherapy was a protective factor affecting patients'RFS and OS.MRD-during consolidation therapy and MRD-at all three time points were all protective factors affecting patients'RFS,OS and CIR.Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients'RFS and CIR,and MRD-during consolidation therapy was a protective factor affecting patients'RFS,OS and CIR.Conclusion:Early achievement of CR and MRD-in adult AML patients,especially MRD-during consolidation therapy,is a marker of good prognosis,and flow cytometry is the most commonly used method for MRD detection in AML patients.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T₂ fracture, 1 case of T₃ fracture, 3 cases of T₄ fracture, 3 cases of T₅ fracture, and 7 cases of T₆ fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T₁ fracture, 5 cases of T₄ fracture, 2 cases of T₅ fracture and 9 cases of T₆ fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.
Female ; Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Robotics ; Blood Loss, Surgical ; Bone Cements ; Retrospective Studies ; Thoracic Vertebrae/surgery*

Objective To explore the protective mechanism of RNA binding protein LIN28 on diabetic nephropathy(DN).Methods LIN28 was overexpressed or knocked down by adenovirus in HEK 293T cells.The gene and functional signaling pathway significantly changed after overexpression of LIN28 were obtained through RNA Seq transcriptome sequencing and bioinformatics analysis.HEK 293T cells were divided into the Control group,the Treatment group,the Adv-LIN28-OE+D-ribose group and the Adv-LIN28-NC+D-ribose group in in vitro LIN28 overexpression studies.And HEK 293T cells were divided into the Control group,the Treatment group,the Adv-shRNA LIN28+D-ribose group and the Adv-shRNA NT+D-ribose group in in vitro LIN28 knockdown studies.ELISA was used to detect the levels of human advanced glycation end products(AGEs)of cells supernatants in the above groups.Western blot was used to detect the expression levels of RAGE,NF-κB and MMP-2 of cells in the above groups.Results The results of RNA-Seq transcriptome sequencing,GO analysis and KEGG analysis showed that overexpression of LIN28 resulted in a significant down-regulation of AGE-RAGE signaling pathway in HEK 293T cells(P<0.05).The results of ELISA showed that compared with the Control group,the cell in the Treatment group produced a large amount of AGEs(P<0.05);compared with the Treatment group,the AGEs level of cells in the Adv-LIN28-OE+D-ribose group was significantly decreased(P<0.05),while the AGEs level of cells in the Adv-shRNA LIN28+D-ribose group was increased(P>0.05).The results of Western blot showed that compared with the Control group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Treatment group were significantly increased(P<0.05);compared with the Treatment group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-LIN28-OE+D-ribose group were significantly decreased(P<0.05),while the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-shRNA LIN28+D-ribose group were significantly increased(P>0.05).Conclusion Overexpression of LIN28 by adenovirus at the cellular level in vitro can lead to significant differential expression of thousands of genes.In particular,it can inhibit the diabetes and complications-related AGE-RAGE signaling pathway,which is critical in the progression of DN disease,and play a role in protecting DN.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4⁺T lymphocytes (CD4) counts >500 cells/μl (compared with having recent CD4 counts <200 cells/μl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adolescent ; Adult ; Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; HIV Infections/epidemiology* ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Marriage ; Young Adult

ObjectiveTo explore the value of plasma free metanephrines， including metanephrine（MN） and normetanephrine（NMN）， collectively referred to as MNs in the diagnosis of pheochromocytoma and paraganglioma （PPGL）. MethodsThe study included 1 631 patients suspected of PPGL from December 2014 to December 2020 in SunYat-sen Memorial Hospital. In these subjects， Plasma free MNs were measured by liquid chromatography-tandem mass spectrometry（LC-MS/MS） before surgery. Receiver operating characteristic （ROC） curves were used to determine the sensitivity and specificity of plasma NMN and MN in the diagnosis of PPGL. ResultsOf the screened patients， 108 patients had pathologically confirmed PPGL and 1 523 patients had definitive diagnoses other than PPGL as a control group. The median value of plasma MN ［0.54（0.17~4.48） nmol/L vs. 0.15（0.11~0.21） nmol/L， P<0.001］ and NMN ［7.48（2.12~15.01） nmol/L vs. 0.32（0.22~0.46） nmol/L， P<0.001］ were significant higher in the PPGL group than in the control group. Using an upper cut-off of 0.395 nmol/L for MN， the sensitivity was 60.2% and the specificity was 97.8%； when using a cut-off of 1.105 nmol/L for NMN， the diagnostic sensitivity was 87.0%， and the specificity was 98.7%. The area under the ROC curve and 95% confidence interval of plasma MN and NMN combined were 0.800（0.743， 0.858）， 0.959（0.932， 0.98） and 0.970（0.944， 0.996）， respectively. Analyzing the false-positive results， it was found that in the control group， 3% of the false-positive cases appeared. The estimated glomerular filtration rate（eGFR） were significantly lower in the false-positive group than in the true-negative group ［74.42（51.04~96.96） mL/min vs. 88.51（72.80~101.83） mL/min， P=0.001］. In 212 patients with eGFR lower than 60 mL/min， the false positive rate was increased to 8%. If the upper limit of the reference interval was increased by 25%， the specificity was increased to 96.7%； when the upper limit of the reference interval was increased by 50%， the specificity was 98.6 %. ConclusionsPlasma free MNs has a great reliability in the diagnosis of PPGL. The negative predictive value is extremely high and close to 100%. Combination analysis of plasma MN and NMN can further improve diagnostic performance. However， a few false positive cases may appear and might be influenced by impaired renal function. In patients with eGFR lower than 60 mL/min， the false positive rate is significantly increasing， which need a 25%-50% increase in the expected upper limit of a reference range to guarantee high specificity.