Aim To investigate the effect of nitidine chloride (NC) on the apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer cell lines HeLa and SiHa were selected as subjects. The cytotoxicity of NC and its inhibitory effect on cell growth were detected by CCK-8 assay and clone formation assay. The effect of NC on the apoptosis of cervical cancer cells was detected by TUNEL assay, and the expression of apoptosis-related proteins was detected by Western blot. The effects of NC on the interaction between p53 and E6AP protein, the level of p53 ubiquitination modification and the stability of p53 protein in cervical cancer cells were analyzed by immunoprecipi-tation assay, ubiquitination assay and Western blot assay. Results NC could significantly inhibit the proliferation and induce apoptosis of cervical cancer cells. NC could inhibit the interaction between tumor suppressor protein p53 and E6AP in cervical cancer cells, reduce the level of p53 ubiquitination modification, delay the degradation of p53 and increase the expression level of p53 protein. Conclusions NC can inhibit the ubiquitination and degradation of p53, improve the expression level of p53 protein, restore its tumor suppressor function, and thus play an anti -cervical cancer role.

ObjectiveTo understand the situation of nosocomial infection in cancer hospitals and its changing trend， so as to provide a basis for adjusting the focus of nosocomial infection prevention and control in cancer hospitals. MethodsData of nosocomial infection quality control indices of Sun Yat-sen University Cancer Center from 2019 to 2021 were obtained through the nosocomial infection monitoring system， and the changes of these indices across the three years were analyzed by Chi-square test and Cochran-Armitage trend test. ResultsFrom 2019 to 2021， the incidence rates of nosocomial infection in this hospital were 0.80%， 0.78% and 0.57%， which decreased significantly year by year （P<0.001）. Among them， surgical site and respiratory system infection were more common， accounting for 35.75% and 31.08%， respectively. Gram-negative bacteria and fungi were the main pathogens. The incidence rate of multidrug-resistant bacteria in hospital increased year by year， from 0.08‰ to 0.14‰ （P<0.001）， among which methicillin-resistant staphylococcus aureus， carbapenem-resistant Enterobacter and bacteria producing ultra-broad spectrum β-lactamase （ESBLs） bacteria increased significantly. The incidence rates of three-tube associated infections were no different across 3 years （P>0.05）， which were still at high levels. ConclusionFrom 2019 to 2021， the prevention and control of nonsocomial infection in the cancer hospital has been improved overall. Meanwhile， the infections of respiratory system and surgical sites， ESBLs related multidrug-resistant bacteria and three-tube are weak links in cancer specialized hospitals， which need to be emphasized and improved.

OBJECTIVE: This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020. RESULTS: After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs. CONCLUSIONS In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
Adult ; Cytochrome P-450 Enzyme System/genetics* ; Female ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant, Newborn ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications/drug therapy*

Aim To study the role of Cx43 hemichannel in rats with acute incision pain. Methods Adult male rats were randomly divided into normal saline group(C group), incision pain group(I group), Gap19 group. Western blot was used to determine the expression of Cx43 and GFAP at 6 h, 3 d and 7 d after paw incision surgery of rats. The rats were intrathecal injected with Gap19 30 min before incision surgery, followed by the measurement of the paw withdrawal threshold to mechanical stimuli at several time points. Immunofluorescence was used to detect the expression of Cx43 and GFAP. ELISA was performed to detect the different inflammatory cytokine levels in rats after surgery. Results Compared with group C, the expression of Cx43 and GFAP of rats increased significantly 6 h after incision surgery in group I, while their expression at postoperative 3 d and 7 d showed no obvious alteration. Compared with the preoperative baseline, the mechanical paw withdrawal threshold in I group and Gap19 group rats was significantly reduced at 2 h, 6 h, 24 h and 3 d post-incision(P<0.01), but it had no obvious change on postoperative 7 d. Compared with group I, the mechanical paw withdrawal threshold in rats of Gap19 group increased 2 h, 6 h, 24 h post-incision, while it showed no statistical difference on 3 d and 7 d post-incision. Compared with group C, immunofluorescence results showed that the expression of GFAP and Cx43 in spinal cord dorsal horn astrocytes also increased significantly in Group I 6 h after incision surgery. Compared with group I, GFAP and the expression of Cx43 were markedly reduced in Gap19 group. There was no statistical difference on 7 d post-incision. Compared with those in group C, the inflammation factors including IL-1β, IL-6 and TNF-αobviously increased in group I. However, in contrary to the rats in group I, the rats pretreated with gap19 showed increased expression of Cx43 and GFAP in spinal cord dorsal horn. Conclusions Specific inhibition of Cx43 hemichannel significantly suppresses astrocyte activation and alters the inflammatory microenvironment in the spinal cord dorsal horn and reduces postoperative hyperalgesia in rats with acute incision pain.

OBJECTIVE: To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia. METHODS: By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed. RESULTS: There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (α CONCLUSION The hematological phenotype changes caused by α
Genotype ; Humans ; Mutation ; Phenotype ; Retrospective Studies ; alpha-Thalassemia/genetics*

ObjectiveTo assess the diagnostic efficiency of different diffusion models （DTI， DKI and NODDI） in grading glioma and predicting IDH-1 mutation status， and to further build logistic regression prediction models. MethodsTotally 66 patients （22 females； mean age： 47.8） with pathologically proved gliomas were retrospectively included. All cases underwent bipolar spin echo diffusion examination. Parameters of DKI （MK； Ka； Kr）， DTI （MD and FA） and NODDI （intracellular volume fraction： icvf， orientation dispersion index： odi） were derived. ROIs were manually drawn and corresponding average values were calculated. Logistic regression was performed to build a predictive model. ROC curve was obtained， and Hosmer-lemeshow test was carried out to test the goodness of fit. ResultsDKI， DTI and NODDI parameters were significantly different between HGGs and LGGs （P < 0.01）. And among all diffusion parameters， a further logistic regression model for grading glioma only included age and MK， which showed the highest diagnostic value ［AUC=0.88， AUC 95%CI （0.79， 0.96）］. Hosmer-lemeshow Test present excellent of goodness of fit. With IDH-1 mutation status， NODDI showed no significant value for distinction， whereas DKI and DTI can significantly differentiate IDH-1 mutated and non-mutated glioma （P < 0.05）. Further logistic regression only selected Kr （P <0.01） in the model， which demonstrated the highest diagnostic value ［AUC=0.72， AUC 95%CI （0.59， 0.85）］. ConclusionsDKI is superior to DTI and NODDI in grading gliomas and identifying IDH-1 mutation status. The model of MK value and age variables present the best discriminatory capacity for grading glioma and Kr value may serve as a potential predictive index for identify IDH-1 mutation.

The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (P<0.05), and IMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (P<0.05). Above all, IMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.
Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Expression ; drug effects ; Hepatocytes ; drug effects ; metabolism ; Humans ; Liver ; drug effects ; injuries ; metabolism ; Liver Diseases ; drug therapy ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Pharmacology

OBJECTIVE: To analyze the effect of dexmedetomidine on the inflammatory factors level and cognitive function after femoral head replacement in elderly patients. METHODS: From January 2016 to December 2017, 60 elderly patients(more than 60 years old, and Grade I to II of ASA) treated with femoral head replacement were divided into three groups, and 20 in each group. All patients received midazolam, fentanyl, etomidate, cisatracurium anesthesia induction and sevoflurane inhalation anesthesia maintenance. The patients in group B and group C were first given 1.0 μg·kg⁻¹ of dexmedetomidine 10 minutes during the operation. The maintenance volume was 0.3 μg·kg⁻¹·h⁻¹ of dexmedetomidine(in group B) and 0.6 μg·kg⁻¹·h⁻¹ of dexmedetomidine(in group C) by pumping. The same amount of saline was given to the patients in group A in the same way. The time of extubation, wakefulness and recovery, the simple intelligent mental state score (MMSE), the incidence of postoperative cognitive dysfunction (POCD) and the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and S100β protein expression in the 3 groups were compared. RESULTS: There were significant differences in the time of spontaneous breathing recovery, eye opening tome and the time of extubation, as well as the dosage of propofol among the three groups(<0.05). On the 1st, 3rd and 7th day after operation, there was a significant difference in MMSE score of group B and group C compared with that of group A(<0.05), and MMSE score in group C was significantly higher than that of group B(<0.05). The incidence of POCD was 0.0% (0/20) and the incidence of adverse reactions was 30%(6/20) in group C, but those were 25% (5/20) and 0.0% (0/20) in group A and 5% (1/20) and 10% (2/20) respectively in group B. The difference was statistically significant (<0.05). Before induction of anesthesia, there was no significant difference in the levels of IL-6, IL-10 and S100β protein among the three groups(>0.05); but one hour after the operation, the levels of IL-6 IL-10 and S100β protein in group B and group C was statistically different from those in group A(<0.05). The IL-6 and S100β protein in group C were significantly lower than those in group B (<0.05), and IL-10 was significantly higher than that in group B (<0.05). CONCLUSIONS For elderly patients operated for femoral head replacement, dexmedetomidine can reduce the level of inflammatory factors level and propofol consumption, and the incidence of postoperative POCD is low, indicating a dose dependence of dexmedetomidine. But it is necessary to choose the right dose according to the patient's condition.
Aged ; Cognition ; Delirium ; Dexmedetomidine ; Humans ; Interleukin-6 ; Middle Aged ; Sevoflurane

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.
Aged ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Methylation ; Middle Aged ; Muscle Proteins/metabolism* ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Progression-Free Survival ; Prostatectomy ; Prostatic Neoplasms/metabolism* ; Retrospective Studies ; Risk Assessment ; Treatment Outcome