Objective To explore the sex differences in drug metabolism of sufentanil in Chinese patients based on the mutation classification of cytochrome P450 3A(CYP3A)enzymes.Methods According to the possible effects of combined cytochrome P450 3A4 gene*1G locus(CYP3A4*1G)and cytochrome P450 3A5 gene*3 locus(CYP3A5*3)mutation groups on Chinese population,we added different weights to CYP3A4*1G and CYP3A5*3 polymorphisms and classified patients into 3 groups:GroupⅠ,patients carried either the CYP3A4*1G/*1G allele or both CYP3A4*1/*1G allele and CYP3A5*3/*3 allele;Group Ⅱ,patients with both CYP3A4*1/*1G allele and CYP3A5*1/*3 allele;Group Ⅲ,patients with either the CYP3A4*1/*1 allele or both CYP3A4*1/*1G allele and CYP3A5*1/*1 allele.A single-dose,double-blind,stratified random sampling was performed,and 255 patients undergoing endoscopic surgery in the First Affiliated Hospital of Army Medical University were finally subjected.According to the results of genetic testing,an independent statistician,before operation,randomly selected 30 patients from each stratified group to form a study cohort(male-female ratio of 1∶1)and named each group A,B or C.Clinical investigators and subjects kept double-blind to the results of grouping and genetic testing.After entering the operating room,the subjected 90 patients received a single dose of sufentanil followed by collection of blood samples at 10 time points including 2 min before and from 2 to 120 min after administration.After the surgery,we determined the plasma drug concentration,calculated the pharmacokinetic parameters,and compared the metabolic differences between different genders in each group and unblinded the study.Results The cohort best fitted the two-compartment pharmacokinetic model,and groups A,B and C corresponded to group Ⅰ,Ⅱand Ⅲ,respectively.In different patient groups based on mutatron types of CYP3A enzymes the females had lower plasma drug concentration-time curves at each time point,higher systemic clearance(P≤0.01)and smaller area under the plasma concentration-time curve from zero to infinity(P＜0.05)when compared with the males.In addition,in group Ⅰ,the elimination rate of central compartment and movement rate of drug from central compartment to peripheral compartment were obviously greater in the females than the males(P＜0.05),while the distribution half-life(P＜0.05)and elimination half-life(P＜0.01)were notably longer in the males than the females.In both group Ⅱ and group Ⅲ,the males obtained larger total area under the plasma concentration-time curve than the females(P＜0.05).Conclusion There are sex differences in the drug metabolism of sufentanil in Chinese patients.Women show faster distribution and higher clearance of sufentanil while men present greater drug exposure.Preoperative CYP3A genotyping and intraoperative personalized medication are of great significance to ensure the safety in clinical practice.

Helicobacter pylori(Hp)is a common Gram-negative bacillus causing gastrointestinal infec-tions.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bacteri-cidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other disea-ses by Hp.

Objective:To combine ultrasound and clinical characteristics for predicting the treatment time of strontium 90( 90Sr) radioisotope applicator therapy for pathological scars when the therapeutic effect meets the clinical effective criteria. Methods:From September 2022 to October 2023, 48 patients (90 lesions) with pathological scars who underwent 90Sr radioisotope applicator therapy at the Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University were prospectively collected. The clinically effective criteria of 90Sr radioisotope applicator therapy for pathological scars were defined as a reduction of the superficial height of the scar higher than 50%. All lesions were divided into short period treatment group (2 months, 38 lesions) and long period treatment group (>2 months, 52 lesions) according to the duration of treatment when the therapeutic effect met the clinical criteria. Univariate comparative analyses of ultrasound and clinical characteristics between the two groups were performed. The statistically significant variates were used to build a multivariate logistic regression model for analyzing the independent predictors of the treatment time of 90Sr radioisotope applicator therapy for pathological scars. Results:Family history, blood flow signal, disease duration, age, and scar Young′s modulus were independent predictors of the effective treatment time of 90Sr radioisotope applicator therapy for pathological scars (all P<0.05). By using the selected variables, a predictive model was developed, area under the ROC curve (AUC) were 0.886 (95% CI=0.817-0.955, P<0.001), and the calibration curve showed that the model was well calibrated(χ 2=5.668, P=0.684). Conclusions:The multivariate logistic regression model with family history, blood flow signal, disease duration, age, and scar Young′s modulus could be used to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars, which can help to guide the design of treatment plan, reduce unnecessary radiation damage, and improve patient compliance.

Parkinson's disease(PD)is a degenera-tive disease of the central nervous system characterized by the loss of dopamine(DA)neurons in the dense sub-stantia nigra and the depletion of DA neurons.Clinically,the treatment of PD is mainly supplementing dopamine deficiency or using DA receptor agonists,but these drugs can only alleviate the symptoms of PD patients,but cannot prevent neuronal loss and delay disease progres-sion.Natural bioactive polysaccharides have the advan-tages of multi-target,low toxicity and synergistic effect,and have great potential in the prevention and treatment of PD.Numerous studies have shown that polysaccha-rides can be involved in neuronal protection and preven-tion of neurodegenerative diseases through mechanisms such as oxidative stress,reducing neuroinflammation,and inhibiting anti-apoptosis.①Anti-oxidative stress.Oxi-dative stress is caused by increased reactive oxygen spe-cies(ROS)products and weakened antioxidant capacity,resulting in destruction of lipids,proteins,and DNA.Oxi-dative stress-induced mitochondrial dysfunction is thought to be an important cause of DA neuronal loss in PD mice.Polysaccharides reduce the damage of DA neurons in the substantia nigra by increasing the activity of antioxidant enzymes and inhibiting the formation of reactive oxygen species.② Reduce neuroinflammation.Neuroinflamma-tory response is the main causative factor of neurodegener-ation,microglia are innate immune cells present in the central nervous system,and their continuous activation is a key link in central nervous system neuroinflammation.Polysaccharides can regulate the expression of inflamma-somes,reduce the levels of pro-inflammatory cytokines and cytotoxic factors,inhibit the excessive activation of microglia,reduce PD neuroinflammatory damage,and then exert neuroprotective effects.③ Inhibiting apopto-sis.Apoptosis(APO)is the process of cell death caused by the activation of cell death procedures by various fac-tors.During the pathogenesis of PD,due to changes in the internal and external environment of DA neurons,some apoptosis-related genes cause DA neuronal death by regulating cell death signaling pathways.Polysaccha-rides can reduce the Bax/Bcl2 ratio,weaken the activa-tion of caspase-related proteins,improve the viability of PC12 cells,reduce apoptosis,and protect the activity of dopamine neurons.In summary,traditional Chinese med-icine polysaccharides can effectively treat and improve PD,and its mechanism of action involves anti-oxidative stress,reducing neuroinflammation and apoptosis.There-fore,traditional Chinese medicine polysaccharides have great development potential in the field of medicine and health.

Areca nut is the dried and mature seed of Areca catechu L.in the palm family,which is a medicinal and food resource.It tastes bitter,spicy and warm.It has the functions of killing insects,eliminating accumulation,activating qi and nourishing water.It contains alkaloids,polyphenols,polysaccharides,fatty acids,amino acids,flavonoids,triterpenes and steroids and other chemical components.It has a certain protective effect on the ner-vous system,and mainly includes:① Arecoline con-tained in areca nut can stimulate the sympathetic nerve and simultaneously stimulate M receptor and N receptor,which can be used for the treatment of Alzheimer's dis-ease.② Antidepressant effect.Arecoline can easily pass through the blood-brain barrier and stimulate nerve cell receptors,thus promoting the body's excitement.Total phenols increase the content of monoamine transmitters in the brain by decreasing the content of monoamine oxi-dase,thus exerting therapeutic effect on depression.③ Antioxidant effect.Polyphenols and flavonoids can reduce oxidative damage of nervous system,and their antioxidant capacity is related to their content.④ Anti-inflammatory effect.Areca polysaccharides can exert anti-inflammatory activity by inhibiting the production of NO in macrophages induced by lipopolysaccharide.⑤Improved digestion.Areca nut water extract has a pro-moting effect on gastrointestinal motility,which is not only related to M choline receptor,but also probably related to α-adrenalin receptor.⑥Other effects.Such as anti-throm-bosis,anti-atherosclerosis,hypoglycemia,blood lipid reg-ulation,anti-tumor,anti-allergy,bacteriostasis,etc.This review summarized the chemical composition and phar-macological action of Areca catechu in recent years.It was found that the mechanism of action of Areca cate-chu L.is still unclear and further research is needed to provide basis for scientific utilization of Areca catechu.

Pain is one of the most serious problems plaguing human health today.Drug therapy is one of the main ways to treat pain in clinic.The analgesic drugs commonly used in clinical treatment of pain are often accompanied by many side effects,the analgesic effect is still not ideal.Salvia miltiorrhiza is a traditional medici-nal material with the same origin as food and medicine.It has the functions of promoting blood circulation and removing blood stasis,relieving pain through menstrual circulation,and contains many effective ingredients such as tanshinone and salvianolic acid.Tanshinone is a kind of rosin diterpenoid compound,which mainly consists of o-quinone type and p-quinone type parent nucleus,and tanshinone Ⅱ A is the representative compound.The pharmacological mechanism of tanshinone ⅡA in labor pain mainly includes:① Regulate inflammatory factors.Inflammatory cytokines played an important role in the occurrence and progression of pain.It was found that the analgesic effect of tanshinone ⅡA was related to the anti-inflammatory effect.Tanshinone ⅡA showed anti-injuri-ous activity in various pain models,such as bone cancer pain and sciatic nerve ligation,and related studies found that tanshinone ⅡA could inhibit the expression of inflammatory factors TNF-α,IL-1β and IL-6 in the spinal cord of model rats.In the spinal nerve ligation model,tanshinone ⅡA also promoted the release of anti-inflam-matory cytokine IL-10 in the spinal cord of rats.② Regu-late signal pathways related to regulating spinal cord oxi-dation and apoptosis.Apoptosis and oxidation played an important role in the process of pain.When nerve injury was caused by stimulation,oxidative stress and apopto-sis of nerve cells were involved in the mechanism of hyperalgesia.Tanshinone ⅡA sodium sulfonate could relieve pain by regulating apoptosis-related pathways.In neuralgia model,tanshinone ⅡA could reduce the apop-tosis of spinal cord neurons by inhibiting oxidative stress response in rat spinal cord tissue.In addition,tanshinone ⅡA also decreased the expression of pro-apoptotic protein in spinal dorsal horn of CCI rats.They included caspase-3,Bcl-2,Bax protein,and enhancer binding protein homologous protein,Increased the expres-sion of anti-apoptosis protein Bcl-2.③ Inhibit the activa-tion of spinal cord glial cells.tanshinone ⅡA could exert its labor pain effect by inhibiting the activation of astro-cytes,including inhibiting the expression of chemo-therapy-induced neuralgia,inflammatory pain and inflam-matory cytokines IL-6,IL-1β and TNF-α,and inhibiting the activation of inflammatory signaling pathways related to astrocyte activation.Such as NF-κB signaling path-way,c-Jun N-terminal kinase signaling pathway,etc.In addition,tanshinone ⅡA also inhibited the activation of microglia by inhibiting the expression of CX3CR1 receptor on the surface of microglia and inhibiting the phosphoryla-tion of ERK,JNK and p38 signaling pathways.④ Decr-ease the expression of glutamate receptors in spinal cord.NMDA is an ionic glutamate receptor in the central nervous system,and its subunit NR2B is closely related to pain.The overexpression of NR2B in spinal cord could lead to the decrease of pain threshold,which was an important mechanism of pain generation.The mechani-cal threshold and thermal threshold of CCI rats were increased by tanshinone ⅡA,and the expression of spi-nal dorsal horn 2B subunit was significantly decreased after tanshinone ⅡA treatment in CCI rats.Therefore,it was concluded that the analgesic effect of tanshinone ⅡA on CCI model may be related to the decreased expres-sion of NR2B in spinal dorsal horn.In conclusion,tanshi-none ⅡA can effectively play the role of labor pain,and has great potential for development in the field of medi-cine and health products.

Cervical spondylotic radiculopathy is a common and frequently-occurring disease in the clinical department of orthopedics.It has the highest incidence of cervical spondylosis and has been classified as a difficult disease by the World Health Organization.Cervical spondylotic radiculopathy mainly manifests as root symptoms and signs consistent with the diseased segment,and the symptoms of stiffness,pain and numbness,which seriously affect the physical and mental health and life quality of patients.In clinical practice,the symptoms of cervical spondylotic radiculopathy can be alleviated by physical therapy,acupuncture,etc.Therefore,searching for more effective treatments has become a hot topic of current researches.Manipulations have the advantages of simple operation,quickness,quick effect and high recognition degree,and can achieve therapeutic purpose by improving the dynamic and static balance of cervical spines,correcting joint dislocation and improving blood circulation.Among them,the curative effect of rotational manipulations is more remarkable.The researches on rotational manipulations by domestic and foreign scholars mainly focus on the in vitro and in vivo biomechanics of cervical spines,and the biomechanical researches on the rotational manipulation itself were different.At present,the mechanical research on the rotational manipulation is still in the development stage,and there is no clear conclusion on the similarities and differences of the mechanical parameters and their influence on the mechanical environment of the cervical spine.In this paper,the research progress of biomechanical properties of cervical spine rotational manipulation was summarized to provide a theoretical basis for the mechanism of the rotational manipulation treatment of cervical spondylotic radiculopathy.