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

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Objective:To explore the risk factors for lower extremity deep vein thrombosis (DVT) in patients with a spinal cord injury (SCI).Methods:The medical records of 276 hospitalized SCI patients were analyzed retrospectively. They were divided into a DVT group ( n=63) and a no-DVT group ( n=213). Gender, age, blood type, smoking history, surgical history, the time from SCI to admission, cause of SCI, fracture, SCI segments, American Spinal Cord Injury Association grade and complications were compared between the two groups. Binomial logistic regression was used to isolate the risk factors for lower extremity DVT among such patients. Results:Among 84% of the 63 with a lower extremity DVT, it was a calf muscle venous thrombosis. Anemia, hyponatremia and time from SCI to admission (which ranged from 74 to 195 days) were the most serious DVT risk factors.Conclusions:SCI patients are of high risk for DVT, with anemia and hyponatremia being independent risk factors.

Objective:To analyze the factors influencing the difference in location of cricothyroid membrane between traditional surface palpation and ultrasonic biplane.Methods:One hundred and seven subjects of both sexes, aged 18 yr, underwent neck ultrasound examination in our hospital from August 2021 to December 2021, were selected.The structure of cervical airway was observed by ultrasound.The subjects in whom the structure of cricothyroid membrane was clearly shown were selected.The middle point of cricothyroid membrane was located by otorhinolaryngologist using surface palpation method and by ultrasonic doctor using ultrasonic biplane method.The distance between two positioning points was measured by a ruler.The subjects were divided into accurate group (distance between two points≤3 mm) and difference group (distance between two points>3 mm). The distance between cricoid cartilage and thyroid cartilage (spacing of cricoid cartilage and thyroid cartilage) and distance between the midpoint of cricothyroid membrane and skin (spacing of cricothyroid membrane and skin) were measured by ultrasound.The neck length and the maximum submaxillary distance in head up were measured by a ruler.The factors influencing the difference in location between the two methods were analyzed by multivariate logistic regression.Results:One hundred and four subjects with clear cricoid cartilage and cricothyroid membrane under ultrasound were selected.There were significant differences in the ratio of gender, body mass index (BMI), cricothyroid membrane-skin distance, neck length, and maximum submandibular distance between the two groups ( P<0.05). Multivariate logistic analysis showed that female ( OR=9.091, P<0.001), BMI ( OR=11.214, P=0.001) and increased cricothyroid membrane-skin distance ( OR=5.649, P=0.015) were the factors influencing the difference in location between the two cricothyroid membrane localization methods. Conclusions:Female, obesity (BMI>28.0 kg/m 2) and increased distance between cricothyroid membrane and skin are the factors affecting the difference in location of cricothyroid membrane between ultrasonic biplane method and surface palpation method, and bedside ultrasound is recommended for location in those with the factors mentioned above.

The unique multi perspective and magni-fying effect of laparoscopic surgery make gastric surgery more precise and minimally invasive. The technical innovation of 4K laparoscopy enable surgeons to understand the finer submicrostructure-membrane anatomy. The advantages of perigastric lymph node dissection with less trauma and bleeding under the guidance of membrane anatomy theory are widely recognized. As a common metastatic site of advanced distal gastric cancer, lymph nodes in the infrapyloric region play an important role in radical gastrectomy. Blood vessels variation is common in the inferior pyloric region, and the layer between gastric and mesenteric membrane is complex. Complete resection of the right gastric omentum membrane can yield greater surgical benefits. In this article, the author discuss the key points of lymph node dissection in the subpyloric region based on their surgical experience, aiming to promote the standard surgical procedure of 4K laparoscopic lymph node dissection in the inferior pyloric region based on membrane anatomy.

Objective To investigate the clinical significance of nasointestinal tube placement in facilitating recovery after Roux-en-Y gastric bypass surgery.Methods The clinical data of patients with gastric neoplasms who underwent Roux-en-Y gastric bypass surgery were analyzed retrospectively.28 patients who had nasointestinal tube inserted were compared to 33 patients who didn't.Indicators for nutrition [body mass index (BMI),Nutrition Risk Screening 2002 (NRS 2002) score,serum total protein (TP),albumin (Alb) and prealbumin] and prognosis (bowel sound and anal exhaust or defecation time,anastomotic leakage rate,abdominal abscess or infection,incision infection or delayed healing,postoperative pulmonary infection rate,postoperative hospitalization time,unplanned reoperation or readmission rate) were analyzed.Results There was no statistically significant difference (all P＞0.05) between the two groups at baseline (sex,age,BMI,NRS 2002 score,operation time and blood loss during operation).The two groups had no statistically significant difference (all P＞0.05) in TP,Alb and prealbumin before the operation or at day 2 or day 6 after the operation.There were significant difference between the two groups in partial indicators for nutrition and prognosis:prealbumin at sixth days after operation (t =-2.05,P =0.045),bowel sound (t =7.71,P =0.000),anal exhaust or defecation time (t=4.52,P=0.000),postoperative hospitalization time (t=4.43,P=0.000),incision infection or delayed healing rate (x2 =4.78,P =0.029).No statistically significant difference (all P＞ 0.05) was found in anastomotic leakage rate,abdominal abscess or infection rate,postoperative pulmonary infection rate,and unplanned reoperation and readmission rate (x2=1.94,P=0.164).There was significant difference (Fisher,P =0.029) between patients aged 70 or above in the two groups in terms of postoperative pulmonary infection rate.Conclusions Enteral nutrition via nasointestinal tube after Roux-en-Y operation in patients with gastric neoplasms can promote protein synthesis,facilitate recovery of intestinal function,shorten hospitalization time and accelerate patient recovery.However,extra caution is needed in patients aged 70 or above,and early extubation should be considered based on the lung conditions of these patients.

AIM: To study the role of post-hemorrhagic shock mesenteric lymph (PHSML) drainage on the balance of angiotensin-converting enzyme ( ACE) and ACE2 in the kidney.METHODS:A hemorrhagic shock model was established and then fluid resuscitation was performed to the animals in shock and shock+drainage groups, and the PHMSL was drained in shock+drainage group after fluid resuscitation.After 6 h of resuscitation, the mRNA expression of ACE, ACE2, angiotensin II (Ang II) type 1 receptor (AT1R) and Mas-related G-protein-coupled receptor (MasR), and the levels of Ang II and Ang (1-7) in the renal tissues were observed.RESULTS:Hemorrhagic shock increased the levels of ACE mRNA, AT1R mRNA and Ang II, and decreased the levels of ACE2 mRNA, MasR mRNA and Ang(1-7) in the kid-ney.PHSML drainage abolished the effect of hemorrhagic shock on ACE2 and AT1R mRNA expression.Meanwhile, PHSML drainage reduced the hemorrhagic shock-induced increases in the ratios of ACE/ACE2, Ang II/Ang(1-7) and AT1R/MasR.CONCLUSION:The PHSML drainage restores the balance of ACE/ACE2, which is beneficial to alleviate acute kidney injury following hemorrhagic shock in the mice.

Objective To analysis effect of midazolam combined with etomidate on liver function, malondialdehyde(MDA) , superoxide dismutase (SOD) levels after laparoscopic cholecystectomy.Methods 80 patients who were undergoing laparoscopic cholecystectomy were collected,all patients were randomly divided into control group and experimental group, 40 cases in each group,who were given the appropriate anesthesia induction drugs before surgery.After operation,the serum levels of MDA, SOD, glutathione peroxidase(GSH-Px) and the liver function were detected in all patients. Results After operation, compared with control group, the serum alanine aminotransferase(ALT) , aspartate aminotransferase (AST) and total bilirubin (TBIL)levels were lower in the experimental group (P<0.05);the serum MDA level was lower in the experimental group (P<0.05);the serum SOD and GSH-PX levels were higher in the experimental group (P<0.05) .Conclusion Midazolam combined with etomidate can reduce oxidative stress reaction in patients after laparoscopic cholecystectomy, which is conducive to the recovery of liver function.

Objective To investigate the clinical effect of laparoscopic operation and laparotomy in the treat-ment of uterine fibroids.Methods A retrospective analysis of uterine fibroids and requests to retain the clinical data of 380 cases of uterine of patients,according to treatment methods,they were divided into laparoscopic myomectomy group (group A)and cesarean section uterine fibroids removed surgery group (B group),there were 190 cases,two groups of patients,surgery,clinical effect were analyzed.Results In group A,operation time,postoperative exhaust time,postoperative ambulation time,postoperative VAS score,duration of hospitalization,injection of analgesics appli-cation proportion were (96 ±35)min,(24 ±8.5)h,(12 ±4)h,(2.0 ±1.5),(4.0 ±1.2)d,17.8%,patients in the group B respectively (98 ±28)min,(40 ±12)h,(20 ±8)h,(6.0 ±1.3),(8 ±2)d,84.6% there was a significant differences between the two groups (t=-2.558,33.96,45.810,50.571,34.120,χ2 =169.89,all P<0.05);group A and group B,the amount of bleeding were (186 ±78)mL and (175 ±85)mL,with no significant difference between the two groups (t=1.911,P>0.05);group A,the complication rate was 7.34%,lower than the 12.6%in the group B,there was significant difference between the two groups (χ2 =3.923,P<0.05).Conclusion Laparoscopic myo-mectomy in treatment of uterine fibroids,good effect,less trauma,quicker recovery,shorter hospitalization time of patients,should be further popularized in clinic.

OBJECTIVETo observe dynamic changes of blood lead concentration in rats with long-term toxicity test with Goupi Gao by the flame atomic absorption spectrometry, in order to provide reference for safe administration of Goupi Gao.

METHODThe rats were administered with Goupi Gao by high-dose (7 g x kg(-1)), medium-dose (3.5 g x kg(-1)), low-dose (1.75 g x kg(-1)) by external use for consecutively 90 days. Then, the blood samples were collected from the rats before the administration and at 10, 30, 45, 52, 60, 90 d after the administration respectively, as well as 16 d and 28 d after the drug withdrawal. The samples were dispelled with microwave digestion system and then were determined by graphite furnace atomic absorption spectrometry for blood lead levels.

RESULTAccording to methodological study, the standard curve regression equation in this experiment was A = 0.004 9X + 0. 017, r = 0.999 5, with the detection limit up to 0. 380 microg x L(-1). The RSD was 1.4% by precision checks. Blood lead level of mixed blood samples was 175.77 microg x L(-1), whose RSD was 6. 0%. Blood lead concentration gradually increased after low-dose and medium-dose administration to rats and became stable at the 10th day and the 30th day by high-dose. Dose is directly related to blood lead concentration. Meanwhile, the blood lead concentration decreases after the drug withdrawal.

CONCLUSIONThe method of determination in this experiment is so accurate and reliable that it can be used for the determination of blood lead. Long-term and high-dose external use of Goupi Gao can increase blood lead.

Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Lead ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Atomic ; methods ; Time Factors ; Toxicity Tests