OBJECTIVE: To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis. METHODS: The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells. RESULTS: The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P<0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01). CONCLUSION GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.
Humans ; Cell Proliferation ; MicroRNAs/metabolism* ; Arthritis, Rheumatoid/genetics* ; Gentisates/pharmacology* ; Cell Movement/genetics*

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To investigate the application of 3D printing percutaneous surgical guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture. METHODS: The clinical data of 12 patients with femoral neck fracture from March 2019 to March 2022 were retrospectively analyzed. Patients were divided into observation group and control group according to different operation plans, with 6 cases in each group. The observation group received percutaneous operation guide plate assisted closed reduction and hollow screw internal fixation, while the control group received closed reduction and hollow compression screw internal fixation. The operation time, intraoperative blood loss, fluoroscopy times, and Kirschner needle puncture times were compared between two groups. The location of screws were recordedon postoperative X-ray films, follow-up time, time of complete fracture healing, Harris score of hip joint and the incidence of complications were recorded on postoperative X-ray films. RESULTS: The operation time of observation group (32.17±6.18) min was shorter than that of control group (53.83±7.31) min (P<0.05). The amount of intraoperative bleeding in the observation group (18.33±2.94) ml was less than that in the control group (38.17±5.56) ml(P<0.05). The times of fluoroscopy in the observation group (7.50±1.05) were less than those in the control group (21.00±4.82) (P<0.05). The number of Kirschner needle punctures (8.00±0.63) in observation group was less than that in control group (32.67±3.08) (P<0.05). The follow-up time was(12.88±0.74) months in observation group and (12.83±0.72) months in control group, there was no significant difference between two groups (P>0.05). One year after operation, Harris score of hip joint in the observation group was(82.00±4.52) points, while that in the control group was(81.00±3.41) points, there was no significant difference between two groups(P>0.05). The time of complete fracture healing in the observation group was (7.50±1.05) months, while that in the control group was (7.67±1.21) months, there was no significant difference between two groups(P>0.05). The parallelism of the screws in the observation group was (0.50±0.11) ° and (0.76±0.15) °, which were lower than that in the control group (1.57±0.31) ° and (1.87±0.21) ° (P<0.05). The screw distribution area ratio (0.13±0.02) cm2 in the observation group was higher than that in the control group (0.08±0.01) cm2 (P<0.05). No complications such as necrosis of femoral head, nonunion of fracture, shortening of femoral neck and withdrawal of internal fixation occurred in both groups. CONCLUSION The application of 3D printing percutaneous surgical guide plate improves the accuracy and safety of closed reduction and cannulated screw internal fixation for femoral neck fracture. It has the advantages of minimally invasive, reducing radiation exposure, fast and accurate, shortening the operation time and reducing intraoperative bleeding.
Humans ; Retrospective Studies ; Treatment Outcome ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Bone Screws ; Printing, Three-Dimensional

OBJECTIVES: To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). METHODS: A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. RESULTS: Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). CONCLUSIONS VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.
Child ; Infant ; Female ; Pregnancy ; Infant, Newborn ; Humans ; Infant, Premature ; Infant, Extremely Low Birth Weight ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing/etiology* ; Retrospective Studies ; Infant, Newborn, Diseases ; Infant, Premature, Diseases/etiology* ; Risk Factors

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To compare the detection rate of advanced neoplasia and the number of people needing endoscopy in colorectal cancer screening giving at different starting age in population at high risk. Methods: Based on the screening project of early diagnosis and treatment of colorectal cancer in Jiashan county, Zhejiang province, two rounds of colorectal cancer screening were conducted between January 2007 and December 2020. After excluding participants who were not at high risk or had incomplete information, 27 130 participants and 31 205 participants were finally enrolled in round one and in round two, respectively. The spline analysis based on the generalized additive model was used to describe the trend of detection rate of advanced neoplasia with age. The detection rate and number of people needing endoscopy for the groups with starting age at 50, 45 and 40 years were calculated, and the differences in the detection rate were tested by χ² goodness of fit test. Results: A total of 21 077 (77.69%) participants in round one and 25 249 (80.91%) participants in round two received endoscopy, in whom 1 097 (detection rate=52.05‰) and 1 151 (detection rate=45.59‰) had advanced neoplasia (cancers and advanced adenomas), respectively. The detection rate increased significantly with age, and the detection rate in round one were significantly higher than that in round two (P<0.05). The overall detection rates of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 61.11‰, 56.14‰ and 52.05‰ in round one, and 49.10‰, 46.75‰ and 45.59‰ in round two, respectively. The rates were significantly higher for the group with starting age at 50 years than that with starting age at 40 years in both round one and round two (P<0.05). The numbers of people needing endoscopy of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 17, 18, and 20 in round one, and 21, 22 and 22 in round two. Conclusions: The detection rate of advanced neoplasia increased with age. Starting screening at lower age might contribute to decreased detection rate and increased number of people needing endoscopy. However, the difference was limited.
Adult ; Colorectal Neoplasms/epidemiology* ; Early Detection of Cancer ; Humans ; Mass Screening ; Middle Aged ; Occult Blood

OBJECTIVE: A dynamic gel loaded with lyophilized platelet-rich plasma-chitosan/difunctionalized polyethylene glycol (LPRP-CP) was prepared to investigate its hemostatic antibacterial and promoting wound healing of scald wounds through in vitro and in vivo experiments. METHODS: In this study, normal gauze/blank tablet (Ctrl), LPRP-CP, Chitosan HUCHUANG Powder(Chito P)and ChitoGauze XP PRO group (Chito G group) were set. The hemostatic effect and promoting healing effect of the four groups of materials were evaluated by establishing rabbit ear artery hemorrhage model and superficial Ⅱ° scalded model of skin on the back. The hemostatic time and bleeding amount were calculated and the gross and histological results of scald healing were observed. The antibacterial effect of the four groups of materials was evaluated by antibacterial test in vitro. RESULTS: In the rabbit ear arterial hemorrhage model, the hemostasis of all materials was successful. The hemostatic time of Ctrl, Chito P, LPRP-CP and Chito G groups was 213.33±38.30, 118.33±24.01, 115.00±8.37 and 111.67±11.69 s, respectively. The blood loss was 1233.83±992.27, 346.67±176.00, 193.33±121.47 and 147.50±80.66 mg, respectively. Compared with Ctrl, the hemostasis time of LPRP-CP, Chito P and Chito G group was significantly shorter (P<0.001), and the amount of blood loss of LPRP-CP and Chito G group was decreased (P<0.05). Compared with LPRP-CP, there were no significant differences in hemostatic time and blood loss between Chito P and Chito G group (P>0.05). In the model of superficial Ⅱ° scalded on the back of rabbit, the wound healing rate of LPRP-CP was faster than that of the other three groups at the same time, and the healing effect was perfect. In the antibacterial test in vitro, only LPRP-CP had better anti-S. aureus effect, and all groups had no anti-E. coli effect. CONCLUSION LPRP-CP is an excellent hemostatic material for superficial wounds, and has certain antibacterial and wound healing effects, which has a wide academic value and research prospects.
Animals ; Anti-Bacterial Agents/pharmacology* ; Chitosan/pharmacology* ; Hemorrhage ; Hemostasis ; Hemostatics ; Humans ; Platelet-Rich Plasma ; Rabbits

ObjectiveTo study the inhibitory effect of Banxia Houputang （BHT） on lipopolysaccharide （LPS）-induced inflammation of microglia （BV2） cells and the neuroprotective effect on human neuroblastoma （SH-SY5Y） cells. MethodAfter the neuroinflammatory model was constructed by LPS inducing BV2 cells， model group （LPS 100 µg·L^-1）， administration groups （LPS+1 g·L^-1 BHT， LPS+2 g·L^-1 BHT， LPS+5 g·L^-1 BHT， LPS+10 g·L^-1 BHT）， and blank group were given DEME medium at the same volume. In addition， neuronal apoptosis model was established by co-culture of LPS-induced BV2 cell inflammation medium and SH-SY5Y cells （LPS-DMEM） and was administrated according to the above grouping. Cell viability was detected by Cell Counting Kit-8 （CCK-8） assay. The content of nitric oxide （NO） and that of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by Griess aasay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA levels of TNF-α， IL-1β， interleukin-4 （IL-4）， nitric oxide synthase （iNOS）， and interleukin-10 （IL-10） were measured by real-time polymerase chain reaction （Real-rime PCR）. Western blot was used to detect the expression levels of signal transducer and activator of transcription 3 （STAT3）， Janus kinase 2 （JAK2） and nuclear factor kappa-B （NF-κB p65）， protein kinase B （Akt）， inhibitor of nuclear factor κB α （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax）. ResultCompared with blank group， LPS increased the NO release， levels of TNF-α， IL-1β， IL-6， and iNOS and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3， decreased the content of IL-4 and IL-10 in BV2 cells， and induced apoptosis of co-cultured SH-SY5Y cells （P<0.01）. Compared with model group， BHT reduced the content of NO， TNF-α， IL-1β， and iNOS （P<0.01） and protein expression of Akt， NF-κB p65， IκBα， JAK2 and STAT3 （P<0.01）， elevated the content of IL-4 and IL-10 （P<0.01）， and inhibited the apoptosis of SH-SY5Y cells induced by LPS-DMEM （P<0.01）. ConclusionThis experiment reveals that BHT inhibited LPS-induced inflammation in BV2 cells by regulating Akt/NF-κB/JAK2/STAT3 signaling pathway and showed neuroprotective effects on SH-SY5Y cells.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l^-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml^-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.
Abiraterone Acetate/therapeutic use* ; Adrenal Cortex Hormones/therapeutic use* ; Androstenes ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Dexamethasone/therapeutic use* ; Disease-Free Survival ; Humans ; Male ; Prednisone/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Retrospective Studies ; Treatment Outcome

Objective To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019 (COVID-19) at 6 and 10 months after disease onset. Methods Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed. Results The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1–2 months post polymerase chain reaction confirmation, respectively. However, neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation. Conclusion Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.