Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Objective To explore the value of diffusion-weighted imaging(DWI),amide proton transfer-weighted imaging(APTWI)and glucose chemical exchange saturation transfer imaging(glucoCEST)for predicting lymph node metastasis of rectal cancer.Methods Sixty cases of rectal cancer confirmed by pathology were retrospectively enrolled and divided into metastasis group(n=36)and non-metastasis group(n=24)based on the presence or absence of lymph node metastasis.The apparent diffusion coefficient(ADC)value,as well as the values of magnetization transfer ratio asymmetry at 3.50 ppm and 1.20 ppm(MTRasym3.50 ppm and MTRasym1.20ppm)of the lesions were respectively obtained based on DWI,APTWI and glucoCEST and then compared between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of each parameter alone and their combination for predicting lymph node metastasis of rectal cancer.Results In metastasis group,ADC value of the lesions was lower,while MTRasym3.50 ppm and MTRasym1.20 ppm values were both higher than those in non-metastasis group(all P＜0.05).AUC of the combination of the above parameters for predicting lymph node metastasis of rectal cancer based on ADC,MTRasym3.50ppm and MTRasym1.20 ppm values was 0.970,significantly higher than that of each single parameter(0.858,0.804 and 0.755,respectively;Z=2.442-3.231,all P＜0.05).Conclusion DWI,APTWI and glucoCEST could all be used to predicte lymph node metastasis of rectal cancer.Combination of ADC,MTRasym3.50 ppm and MTRasym1.20 ppm had the highest predictive efficacy.

OBJECTIVE To explore the clinical characteristics of patients with hematologic tumors combined with Fusarium infection and analyze the prevention and control measures.METHODS Six patients with hematologic neo-plasms combined with Fusarium infection diagnosed at the First Medical Center of the People's Liberation Army General Hospital from Apr.2019 to Dec.2023 were selected as research objects.Through retrospective analysis of patients' clinical data,the clinical manifestations,diagnosis,treatment and prevention strategies of Fusarium in-fection in hematologic neoplasms were analyzed.RESULTS All six patients with hematologic neoplasms combined with Fusarium infection were neutropenic or deficient patients,with main symptoms including moderate fever,painful skin nodules,rash,skin broken and crusted,and scrotal swelling and pain.Patients with severe neutrophil deficiency were susceptible to blood-borne Fusobacterium infections.Four patients had a markedly elevated G-test and Fusorium was first detected by microbiome metagenomic next-generation sequencing(mNGS)in blood,earli-er than traditional pathogenic culture methods.Five patients had Fusarium detected in urine or stool cultures.All six patients received empirical antibacterial and antifungal treatments,but the fungal infection treatment effects were poor.Treatment was adjusted according to the pathogenetic findings,mainly using a combination regimen based on liposomal amphotericin B or posaconazole tablets,with three patients cured and three death.Two pa-tients were from the same ward with a sixteen-day interval.Although no evidence of infection transmission was found,there was still a risk of cross-infection in patients with hematological malignancies and severe immunodefi-ciency.Measures for the prevention and control of hospital-acquired infections were implemented for patients with Fusarium infection and the ward.CONCLUSIONS The clinical manifestations of patients with hematological tumors combined with Fusarium infection are complex and varied with high mortality rates.MNGS testing is valuable in the early diagnosis of Fusarium infection,and it is necessary to explore new treatment options and hospital-ac-quired infectious disease prevention and control measures to improve the prognosis.

Objective:To review the Minimal Clinically Important Difference(MCID)of EQ-5D-3L calculated by anchor-based method,evaluate the reliability of existing MCID,and provide reference thresholds for the interpretation of clinical research results.Methods:CNKI,PubMed,Embase and others were searched from inception to June 30,2023.The nonparametric tests were used to analyze the impact of statistical methods and sample size on MCID.Results:A total of 51 studies were eventually included.Studies were primarily prospective in design,32 studies focused on musculoskeletal disorders,37 studies used a single anchor,45 studies adopted patient-perspective anchor,and the Receiver Operating Characteristic(ROC)curve was the main statistical analysis method.A total of 160 MCID were obtained from 51 studies,ranging from 0.003 to 0.540,and only 3 MCID from 2 studies were rated as"high reliability"across all core items of the evaluation instrument.It is found that statistical analysis methods,sample size,and measurement time interval all significantly affect MCID.Conclusion:The disease type in EQ-5D-3L MCID studies were not abundant and unbalanced,and the heterogeneity of MCID measured in the included studies was high.The reliability evaluation results showed that the existing MCID has poor reliability in all items except the first and second items of the evaluation instrument.

Objective:To investigate the efficacy of cytoreductive radical prostatectomy (CRP) in patients with oligometastatic prostate cancer, and to assess its impact on progression-free survival (PFS), overall survival (OS), as well as the incidence and severity of complications.Methods:A prospective, monocentric non-randomized controlled trial including 80 cases of oligometastatic prostate cancer admitted to the Second Affiliated Hospital of Air Force Military Medical University from January 2020 to June 2024 was conducted. There were 40 patients each assigned to CRP group and no local treatment (NLT) group. The study used multivariate analysis to account for potential biases, analyzed the effects of CRP on PFS, OS as well as circulating tumor cell (CTC) and DNA methylation status. Meanwhile, the incidence and severity of complications were recorded. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for inter-group comparison. Count data and rank data were expressed as number of cases and percentage, and Chi-test was used for comparison between groups. Kaplan-Meier method was used to calculate PFS and OS, and Log-rank test was used to compare differences between groups. Multivariate analysis was performed using Cox proportional hazard regression model. A time-dependent Cox regression model was used to consider the effect of follow-up time on the results. Results:The PFS and OS in the CRP group were significantly better than those in the NLT group. The PFS rates in CRP group and NLT group at 12 months were 60% and 35% ( P=0.030). The OS rates at 12 months in the CRP group reached 80%, compared to 50% in the NLT group ( P=0.040). The level of CTC in the CRP group decreased from 50 cells/mL at first month to 5 cells/mL at 12th month, and the DNA methylation status decreased from 0.75 at first month to 0.30 at 12th month, which were significantly better than those in the NLT group ( P<0.05). The incidence of complications decreased gradually from first month to 12th month, with the CRP group from 30% to 10%, and the NLT group from 25% to 12% ( P=0.080). Although the severity of complications was slightly higher in the CRP group than in the NLT group at the early stage, the difference in severity gradually narrowed and eventually became similar between the two groups by the 12th month of follow-up. Conclusion:CRP significantly prolonged PFS and OS in patients with oligometastatic prostate cancer, reduced tumor burden, and despite a higher incidence of early complications, overall safety was good.

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

Objective To evaluate the clinical characteristics of human immunodeficiency virus (HIV) infected patients with peripheral lung masses (PLMs), and to assess the diagnostic utility of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant PLMs. Methods A retrospective analysis was performed on the clinical data of 69 patients with PLM treated in Shanghai Public Health Clinical Center from January 2020 to December 2023. All patients underwent percutaneous biopsy, and were categorized into benign group (n＝36) and malignant group (n＝33). 25 patients were HIV-positive and 44 patients were HIV-negative. The clinical features and CEUS parameters in patients were compared across these groups. Results Patients with malignant masses were significantly older than those with benign masses (P＜0.05). In the malignant group, HIV-negative patients exhibited significantly larger tumor diameters compared to HIV-positive patients (P＜0.05); in the HIV-positive patients, no significant difference in tumor size was observed between benign and malignant masses. 19 patients underwent CEUS. 10 malignant masses, irrespective of HIV status (10 positive and 9 negative), commonly presented with indistinct margins, delayed enhancement, heterogeneous perfusion, and delayed peak enhancement on CEUS. 9 benign masses showed earlier peak enhancement compared to 10 malignant masses (P＜0.05); no significant differences were observed in the initiation and washout time of enhancement between benign and malignant masses. In HIV-positive patients, 5 benign masses frequently demonstrated discrepancies between CEUS findings and pathological results. Conclusions The clinical and CEUS characteristics were different between benign and malignant PLMs. However, CEUS shows limited accuracy in distinguishing benign and malignant PLMs, underscoring the need for pathological confirmation.

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

Objective: To investigate the timing of puberty onset among primary school students, so as to provide the reference data for early identification of children with suspected precocious puberty. Methods: A study was conducted from October 23 to November 7, 2023, involving 10 225 students(5 412 boys, 4 813 girls) from grade 1 to 6 of four campuses in Meiling Primary School in Yangzhou. Breast development in girls and external genitalia in boys was assessed via visual inspection and palpation, with pubertal stages classified using the Tanner staging method. Puberty onset timing was determined based on age/sex reference values from Chinese Han children s pubertal milestone indicators. Descriptive analysis was performed using SPSS 26.0. Results: The median age for testicular volume reaching 4 mL in boys was 10.49 years, while the median age for breast development onset in girls was 9.70 years. Among boys with testicular volume ≥4 mL, 16.6%( n =217) were identified as suspected early puberty cases; among girls with Tanner stage Ⅱ and Ⅲ, 123(9.4%) and 165(18.5%) showed earlier breast development than the reference range. Overall, 14.4% of students exhibited suspected precocious puberty. Conclusion The onset age of puberty for girls in primary schools of Yangzhou aligns with findings from other regions, while boys show earlier pubertal initiation.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*