Objective To establish the HPLC fingerprints for the different extracts from Coptidis Rhizoma，and investigate the spectrum-effect relationship between HPLC fingerprints and anti-Staphylococcus aureus activity in vitro to analyze the pharmacodynamic material basis. Methods Nine kinds of Coptidis Rhizoma extracts were prepared, and establish the HPLC fingerprints for them. The antibacterial rate of each extract was determined by the broth microdilution method with Staphylococcus aureus as the test bacteria. The grey relational analysis （GRA） method was used to analyze the correlation between the fingerprint data and the in vitro antibacterial test data. Results The HPLC fingerprints of nine kinds of Coptidis Rhizoma extracts were established, nine common characteristic fingerprint peaks were calibrated, and 5 peaks were identified by the reference substance comparison method. GRA analysis experiments showed that the correlation between nine peaks and antibacterial effect was 0.559 1~0.803 3; and the peak 3, peak 8 （palmatine hydrochloride）, peak 9 （berberine hydrochloride） were positively correlated with the inhibition of Staphylococcus aureus,while the peak 9 （berberine hydrochloride） had the strongest effect, and its correlation degree was 0.803 3. Conclusion The effective substance of antibacterial was preliminarily determined through the study of spectrum-effect relationship for Coptidis Rhizoma extracts,which may be the alkaloids, mostly containing hydrochloride, which provided a reference for further research on the pharmacodynamic material basis of Coptidis Rhizoma.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.

Objective To investigate the effect and mechanism of circular RNA nuclear receptor interacting protein 1(circNRIP1)expression on exhaustion of CD8+T cells in cervical cancer cells.Methods Real-time quantitative PCR was used to detect the expression of circNRIP1 in cervical epithelial cells HCerEpic and cer-vical cancer cells C-33A,Hela,SiHa,and CS121.C-33A cells were divided into Vector group,circNRIP1 group,and circNRIP1+miR-138-5p group,while CS121 cells were divided into sh-NC group,sh-circNRIP1 group,and sh-circNRIP1+miR-138-5p inhibitor.Human peripheral blood CD8+T cells were extracted,and C-33A cells in Vector group and circNRIP1 group were co-incubated with CD8+T cells for 24 hours(CD8+T/Vector group and CD8+T/Vector group).CS121 cells in sh-NC group and sh-circNRIP1 group were co-incu-bated with CD8+T cells for 24 hours(CD8+T/sh NC group and CD8+T/sh-circNRIP1 group).Cytotoxicity experiments were conducted to detect the killing ability of CD8+T cells,ELISA was used to detect the levels of interleukin(IL)-2,interferon(IFN)-γ,and tumor necrosis factor(TNF)-α in the cell supernatant.Flow cy-tometry was used to detect the expression of programmed death receptor-1(PD-1),T cell Immunoglobulin domain and Mucin domain protein-3(TIM3),and lymphocyte activation gene 3(LAG3)in CD8+T cells.Dual luciferase reporter gene experiments were conducted to verify the targeting relationship between circNRIP1 and miR-138-5p,as well as the targeting relationship between miR-138-5p and PD-L1.Results The expres-sions of circNRIP1 in C-33A,Hela,SiHa,and CS121 cells were significantly higher than those in HCerEpic(P＜0.05).The killing ability of CD8+T cells against C-33A cells in the circNRIP1 group was lower than their killing ability against Vector group cells.The levels of IL-2,IFN-γ,and TNF-α secreted by CD8+T cells in the CD8+T/circNRIP1 group were significantly lower than those in the CD8+T/Vector group(P＜0.05),and the levels of PD-1,LAG-3,and TIM-3 expressed by CD8+T cells in the CD8+T/circNRIP1 group were al-so significantly higher than those in the CD8+T/Vector group(P＜0.05).The killing ability of CD8+T cells against sh-circNRIP1 group CS121 cells was higher than their killing ability against sh-NC group cells(P＜0.05).The levels of IL-2,IFN-γ,and TNF-α secreted by CD8+T cells in the CD8+T/sh-circNRIP1 group were significantly higher than those in the CD8+T/sh-NC group(P＜0.05).The PD-1,LAG-3,and TIM-3 levels of CD8+T cells in the CD8+T/sh-circNRIP1 group were also significantly lower than those in the CD8+T/sh-NC group(P＜0.05).The results of the dual-luciferase reporter gene experiment showed that miR-138-5p was the target gene of circNRIP1,and PD-L1 was the target gene of miR-138-5p.Conclusion circNRIP1 can in-duce the exhaustion of CD8+T cells by upregulating the expression of PD-L1.

Objective To investigate the expression of circular RNA ubiquitin-associated protein 2(circ-UBAP2)and RAS-related C3 botulinum toxin substrate 1(Rac1)in cervical cancer tissues and their relation-ship with radiotherapy efficacy and prognosis.Methods A total of 96 patients with cervical cancer admitted to the hospital from January 2019 to May 2021 were selected as the research subjects.Detect the expression of circ-UBAP2 and Rac1 in the cancer tissues and adjacent tissues of the patients.The clinical data of the patients were recorded.According to the radiotherapy efficacy,they were divided into patients with effective radiother-apy(n=62)and patients with ineffective radiotherapy(n=34),and the relationship between the expressions of circ-UBAP2 and Rac1 and the radiotherapy efficacy was analyzed.The survival conditions of the patients were followed up for 3 years and they were divided into the survival group(n=81)and the death group(n=15),and the clinical data of the two groups were compared.The relationship between the expressions of circ-UBAP2 and Rac1 and the survival prognosis of patients was analyzed by Kaplan-Meier.The risk factors influ-encing the prognosis of patients were analyzed by Cox regression.Results The circ-UBAP2 expression and the positive rates of Rac1 expression in cancer tissues were both higher than those in adjacent tissues,and the difference was statistically significant(P＜0.05).The effective rate of radiotherapy in patients with high ex-pression of circ-UBAP2 and Rac1 in cancer tissues was lower than that in patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).The 3-year overall survival rate and average survival duration of patients with high expression of circ-UBAP2 and Rac1 in cancer tissues were lower than those of patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).There were statistically significant differences in clinical stage,tumor differentiation degree,expressions of circ-UBAP2 and Rac1,and the proportion of lymph node metastasis between the two groups(P＜0.05).The results of Cox regression analysis showed that clinical stage Ⅱ B-Ⅲ,poorly differen-tiated tumor degree,high expression of circ-UBAP2 and Rac1,and lymph node metastasis were risk factors af-fecting the prognosis of patients(P＜0.05).Conclusion circ-UBAP2 and Rac1 are abnormally highly ex-pressed in cervical cancer tissues and are related to the radiotherapy efficacy and prognosis.

Background With the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. Objective To establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. Methods A certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L⁻¹ and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. Result After the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L⁻¹ (R>0.999), with 0.3 ng·L⁻¹ limit of detection and 1.0 ng·L⁻¹ limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. Conclusion Combined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

Objective:To explore the effect of multidisciplinary management combined with 60-second high-risk diabetic foot screening in diabetic foot.Methods:From January to December 2022, 138 patients with diabetic foot were selected from Xinxiang Central Hospital by convenience sampling. The patients were randomly divided into a control group and an observation group, with 69 cases in each group. Control group implemented routine follow-up management of diabetic foot, and observation group carried out multidisciplinary management combined with 60-second high-risk diabetic foot screening on the basis of control group, and the intervention lasted for six months. The progress of Wagner grading of diabetic foot and foot self-care were compared between the two groups.Results:After intervention, the number of Wagner grading progression patients in observation group and control group was four cases (5.80%) and 10 cases (14.49%), respectively. The number of progression patients in observation group was less than that in control group, and the difference was statistically significant (χ 2=4.161, P=0.041). The total score and dimension scores of diabetic foot self-management in the two groups after the intervention were higher than those before the intervention, but only the scores of observation group before and after the intervention were statistically significant ( P<0.05). After intervention, the total score and dimension scores of diabetic foot self-management in observation group were higher than those in control group, with a statistically significant difference ( P<0.05) . Conclusions:Multidisciplinary management combined with 60-second high-risk diabetic foot screening can effectively delay the progress of diabetic foot and improve patients' foot self-care.

Cancers are significant diseases that seriously threaten human health.Accurate diagnosis and efficacy assessment are the keys to improving clinical treatment and reducing cancer-related mortality.With the further development of artificial intelligence in medical imaging,radiomics and pathomics have emerged and shown great potential in diagnosing and treating cancers.However,at the same time,radiomics and pathomics have also shown their limitations of lacking biological validation and macroscopic properties of cancers,respectively.Combining them across modalities and scales is necessary to complement each other's strengths.This paper reviewed the progress,limitations,and future perspectives of radiomics and pathomics workflows and their combined application in cancers.

Objective:To evaluate pulmonary hypertension (PH) in Chinese people living with human immunodeficiency virus (HIV) receiving long-term anti-retroviral therapy (ART) and those who had not received ART for HIV infection, and to analyze the risk factors for PH in HIV infected individuals, so as to provide evidence for the monitoring and management of cardiovascular diseases in people living with HIV in China.Methods:HIV infected individuals who received long-term ART were from the NCT04463810 study cohort. In addition, using propensity score matching method, gender matched HIV infected individuals who had not received ART were selected as controls from the NCT00872417 and NCT01844297 studies. This study was a retrospective and observational clinical study. Basic data, clinical visit and cardiac Doppler ultrasonography data were collected to analyze the prevalence of PH and risk factors for PH in people living with HIV. Chi-square test and multivariate logistic regression were used for statistical analysis.Results:Among the 318 HIV infected individuals, 159 underwent long-term ART and 159 did not receive ART, which were divided into long-term ART group and ART-na?ve group, respectively. Among 318 HIV infected individuals, 30 cases (9.4%) experienced PH, including 23 cases (7.2%) with critical PH, six cases (1.9%) with mild PH, one case (0.3%) with moderate PH, and there was no severe PH. The prevalence of PH in the long-term ART group was 5.0%(8/159), which was lower than that in the ART-na?ve group (13.8%, 22/159). The difference was statistically significant ( χ2=7.21, P=0.012). Multivariate analysis showed that older age (odds ratio ( OR)=1.064, 95% confidence interval ( CI) 1.019 to 1.111, P=0.016) and unsuppressed HIV status ( OR=2.660, 95% CI 1.041 to 6.797, P=0.041) were independent risk factors for PH of people living with HIV. Conclusions:The prevalence of PH in people living with HIV with long-term ART is lower than that of ART-na?ve people living with HIV. Older age and unsuppressed HIV status are independent risk factors for PH in people living with HIV. Cardiac Doppler ultrasonography is helpful for the early screening of PH in people living with HIV. ART should be actively performed to reduce the incidence of PH in people living with HIV.