NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Purpose To observe the clinicopathological changes of gastric adenocarcinoma of fundic-gland mucosa type(GA-FGM).Methods The clinicopathological data of 4 cases of GA-FGM was analyzed retrospectively.The expression of MUC5AC and MUC6 was detected by immunohistochemical method,and review relevant literature.Results The tumor dif-ferentiated into gastric foveal epithelium and gastric fundus gland.The differentiated part of the pits consists of high colum-nar neoplastic epithelium with low atypia,which can be papilla-ry,villous or tubular morphology.Immunohistochemical staining showed MUC5AC expression.The gastric fundus gland differen-tiated into cervical mucous cells,main cells and parietal cells,and was positive for MUC6 immunohistochemistry.Conclusion Gastric adenocarcinoma of fundic-gland mucosa type has u-nique pathologic characteristics,which is very difficult to diag-nose in biopsy,and the morphology of GA-FGM overlaps with that of gastric fundus adenocarcinoma,so we need to strengthen our understanding.Immunohistochemistry plays an important role in differential diagnosis.

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

Objective:To investigate the effect and mechanism of Grifola frondosa extract on inflammatory response of colon tissue in rats with ulcerative colitis(UC)by regulating interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Forty SD rats were randomly divided into blank control group,UC model group,Grifola frondosa treatment group,western medicine treatment group and combined treatment group,with 8 rats in each group.After UC rats were established by free drinking 3%DSS for 7 days,the treatment group were given Grifola frondosa extract 10 mg/(kg·d),sulfasalazine 0.3 g/(kg·d),and the same amount of two drugs,for 14 consecutive days.During the experiment,general state of rats were observed,and the disease activity index(DAI)score was calculated;pathological changes of rats colon tissue were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue were detected by Western blot;content of IL-6 in rats serum was detected by ELISA;protein contents and expressions of IL-6R and MPO in rats colon tissue were determined by immunohistochemistry.Results:Compared with blank control group,general state of rats in UC model group was poor,DAI score was increased,obvious tissue mucosal defects and inflammatory cell infiltration were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue and contents of IL-6R and MPO were significantly increased(P<0.01);content of IL-6 in rats serum was significantly increased(P<0.01),the difference was statistically significant.Compared with UC model group,general condition of rats in each treatment group was improved,DAI score was decreased,HE staining showed that mucosal defects were improved to varying degrees,and occasionally inflammatory cell infiltration was observed;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in colon tissue were significantly decreased(P<0.01),contents of IL-6R and MPO in colon tissue and content of IL-6 in serum were significantly decreased(P<0.01 or P<0.05),the differences were statistically significant.Conclusion:Grifola frondosa extract can reduce the inflammatory response in colon tissue of UC rats by regulating expressions of IL-6/JAK2/STAT3 signaling pathway related factors.

As the foremost among the four examinations in traditional Chinese medicine （TCM）， inspection and related equipment research face challenges in landing and transformation due to variations in evidence quality， lack of standardization， insufficient algorithm transparency， and poor reliability and stability of decision-making. Against the backdrop of rapid development of emerging technologies such as big data， the internet of things， and artificial intelligence， coupled with macro policy support from the government， digital and intelligent generalized inspection in TCM has emerged， with the aim of utilizing digital technologies to overcome the limitations of naked-eye inspection and comprehensively perceive and analyze facial and bodily expressions. The research in this field intelligently correlates Zang-fu organ functions with health conditions and disease progression and establishes a technical system for digital and intelligent inspection， multi-dimensional and multimodal perception， fusion analysis， and decision-making. This system aims to enhance the accuracy of disease risk warning and diagnosis， bridging the gap between inspection equipment and assistance in clinical decision-making. From an evidence-based perspective， this paper systematically examines the research ideas of digital and intelligent inspection and the development of related equipment， deeply explores how to propose clinical practice-oriented key scientific issues， comprehensively acquire and co-apply multi-dimensional data， establish precise inspection models driven by digital intelligence， optimize standards to enhance equipment interoperability and reliability， construct post-effect evaluation mechanisms to promote improvement， and actively address potential risks such as the black box nature and information security in the application of intelligent technology. This paper not only demonstrates the tremendous potential of digital technologies in improving the accuracy and clinical application efficiency of inspection but also provides new perspectives and ideas for the modernization of inspection in TCM， paving the way for the application of inspection in the global medical and health field.

Objective To explore the effect of muscle energy technique(MET)on dynamic posture control and lumbar neuromuscu-lar function in patients with non-specific low back pain. Methods From March to June,2022,30 college students with non-specific low back pain from Shandong Sport Universi-ty were randomly divided into control group(n=15)and intervention group(n=15).The control group received health education,and the intervention group received MET,for four weeks.They were assessed with Visual Ana-logue Scale(VAS)of pain,Oswestry Disability Index(ODI),Y-balance test and trunk flexion-relaxation test be-fore and after intervention. Results VAS scores decreased in both groups after intervention(|t|>2.449,P<0.05),and it was less in the intervention group than in the control group(t=-5.068,P<0.001);while ODI score decreased in the intervention group(t=4.785,P<0.001),and it was less in the intervention group than in the control group(t=-2.895,P=0.007);the performance of Y-balance test increased(t=-3.662,P=0.003)in the intervention group,as well as flexion-re-laxation ratio of multifidus(t=-2.460,P=0.029). Conclusion MET is effective on alleviating pain and lumbar dysfunction,improving dynamic posture control and en-hancing the function of the multifidus during flexion in patients with non-specific low back pain.

Human genetic resources are an indispensable part of national natural science and technology resources,as well as an important strategic resource for safeguarding national security,public health,and social public interests.To promote the effective protection and rational utilization of human genetic resources,as well as improve and optimize the local human genetic resources management system in China,this paper summarized the current situation of administrative approval and supervision of national human genetic resources from 2004 to 2021 by sorting out the national human genetic resources management policies and regulations.Furthermore,the current situation and progress of local human genetic resources management in China were understood from three aspects,including development planning and programs of human genetic resources,administrative licensing and penalties,and the construction of management expert committees.The main problems of local human genetic resources management in China were discussed and analyzed,such as unclear supervision,difficulty in supervision and inspection,and capacity for services.Based on the causes of the problems and the local management work,specific countermeasures and suggestions were put forward from the perspective of clarifying the regulatory policies and procedures for human genetic resources,improving the supervision and inspection mechanisms,and improving the management and service capabilities.

[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.

Objective:To investigate the prognostic value of the combined preoperative albumin-globulin score (AGS) and skeletal muscle index (SMI), referred to as the CAS classification, in predicting postoperative outcomes in patients with pancreatic cancer.Methods:The clinical data from 265 patients who underwent surgical treatment and were pathologically confirmed to have pancreatic cancer at the Affiliated Hospital of Qingdao University between January 2012 and December 2022 were retrospectively analyzed. Patients were randomly divided into a training group ( n=184) and a validation group ( n=81) in a 7∶3 ratio. Patients' age, gender, body mass index (BMI), smoking history, alcohol consumption history, previous history of metabolic diseases, AGS, SMI, and CAS classifications within 7 days before surgery, preoperative upper abdominal CT imaging features, presence of vascular and neural invasion, and lymph node metastasis were recorded. Patients with AGS grade 0 were classified into the low AGS group ( n=48), while those with AGS grades 1 and 2 were classified into the high AGS group ( n=136). The optimal cutoff value for SMI was determined using X-tile software: male patients with SMI>42.6 cm 2/m 2 or female patients with SMI>37.8 cm 2/m 2 were categorized into the high SMI group ( n=125), while those below these thresholds were categorized into the low SMI group ( n=59). Patients with AGS grade 0 and SMI>42.6 cm 2/m 2 for males or >37.8 cm 2/m 2 for females were classified into the CAS grade 1 group (n=32). Patients with AGS grades 1 or 2 and SMI ≤42.6 cm 2/m 2 for males or ≤37.8 cm 2/m 2 for females were classified into the CAS grade 3 group ( n=43). The remaining patients were classified into the CAS grade 2 group ( n=109). Clinical characteristics were compared across these groups. Cumulative survival rates were estimated using the Kaplan-Meier method, and survival curves were plotted to analyze the relationship between AGS, SMI, and CAS classifications and overall survival after pancreatic cancer surgery. Differences among groups were assessed using the Log-Rank test. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of AGS, SMI, and CAS on postoperative survival. Results:Compared to the high AGS group, the low AGS group exhibited higher SMI values [(46.17±9.63) cm 2/m 2vs (44.11±7.43) cm 2/m 2], and a lower incidence of lymph node metastasis (16 vs 66, 33.3% vs 48.5%). The mortality rate in the low AGS group was 50.0%(24/48), significantly lower than the 70.6% (96/136) observed in the high AGS group, with a median overall survival of 22.08 months (95% CI 16.87-29.62) longer than 13.1 months (95% CI 8.84-18.82) in high AGS group. Compared to the low SMI group, the high SMI group had a lower prevalence of metabolic diseases (26.4% vs 44.1%). The mortality rate in the low SMI group was 78.0% (46/59), higher than the 58.4% (73/125) in the high SMI group, with a median overall survival of 12.97 months (95% CI 9.37-18.20) obviously shorter than 16.20 months (95% CI 10.7-24.12) in high SMI group. Lymph node metastasis rate for CAS grade 1, 2, and 3 was 34.4% ( n=11), 44.0% ( n=48), and 62.8% ( n=27), respectively, with corresponding mortality rate of 34.3% (11/32), 67.9% (74/109), and 79.1% (34/43), and median overall survival time of 25.55 months (95% CI 19.49-30.07), 14.10 months (95% CI 10.22-19.14), and 12.5 months (95% CI 8.53-18.00), respectively. All the differences were statistically significant (all P value <0.05). Kaplan-Meier survival analyses demonstrated that patients in the low AGS group had significantly longer overall survival than those in the high AGS group in both the training and validation cohorts. Similarly, patients in the high SMI group had longer overall survival compared to those in the low SMI group. Notably, patients in CAS grade 1 exhibited the longest overall survival, whereas those in CAS grade 3 had the shortest. ROC curve analysis revealed that the AUC for CAS classification was superior in the training cohort (0.649) compared to AGS (0.588) and SMI (0.593), and in the validation cohort (0.644) compared to AGS (0.587) and SMI (0.577). Conclusions:CAS classification could effectively predict postoperative prognosis in pancreatic cancer patients, with higher CAS grades correlating with poorer outcomes.

Objective:By summarizing and analyzing the results of the inter-laboratory quality evaluation of hematoxylin-eosin(HE)staining organized by the Pathological Equipment Branch of Chinese Medical Equipment Association,to timely identify problems and summarize experience,and to improve the level of HE staining and the ability of inter-laboratory quality control management in medical institutions.Methods:The results of the national routine pathology HE staining inter-laboratory quality evaluation sponsored by the Pathology Equipment Branch of the China Medical Equipment Association in 2022 and 2023 were collected,and the grades,tissue types and evaluation results of the evaluation units participating in the inter-laboratory quality evaluation of HE staining were statistically analyzed.Results:In 2022,a total of 165 evaluation units participated in the inter-laboratory quality evaluation of HE staining with valid results,and 156 in 2023.HE stained tissue types included uterine tissue,gastrointestinal tissue,lung tissue,and breast tissue.The qualified rates of HE staining of the participating units in 2023 were 82.42％(136/165),which was higher than that of 90.38％(141/156)in 2022,the difference was statistically significant(x2=4.30,P＜0.05).There was no statistically significant difference in the staining pass rate of the tertiary hospitals participating in the evaluation in 2023 compared with that in 2022(P＞0.05).The qualified rates of secondary hospitals and non-public medical institutions were 100％and 92.37％,respectively,which were higher than those in 2022,the difference was statistically significant(x2=3.91,5.93,P＜0.05).The qualified rates of inter-laboratory quality evaluation of uterine tissue,gastrointestinal tissue,lung tissue and breast tissue evaluated in 2023 were 92.31％(144/156),91.03％(142/156),91.03％(142/156)and 91.67％(143/156),respectively,which were higher than those in 2022,the differences between uterine tissue and gastrointestinal tissue in two-year evaluation were statistically significant(x2=6.33,5.93,P＜0.05).There was no statistically significant difference in the two-year evaluation between lung tissue and breast tissue(P＞0.05).Conclusion:The continuous participation of medical institutions in the inter-laboratory quality evaluation activities of HE staining can improve the quality of routine pathological HE staining,improve the level of pathological technicians,and reduce the staining differences caused by different unit properties and specimen types.