OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT

Objective To investigate the clinical efficacy of Bushen Jianpi Recipe(mainly composed of Astragali Radix,Epimedii Folium,Dioscoreae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Cervi Cornus Colla,Astragali Complanati Semen,Polygoni Multiflori Radix Preparata,Polygonati Rhizoma,Puerariae Lobatae Radix,and Rhei Radix et Rhizoma)on patients with type 2 diabetes mellitus(T2DM)complicated with dyslipidemia and differentiated as spleen-kidney deficiency type,and to observe its effect on the level of adiponectin(ADP).Methods Ninety patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type were randomly divided into western medicine group,Chinese medicine(CM)group,and combination of CM and western medicine group(hereinafter referred to as combination group),and each group had 30 patients.All of the 3 groups were given conventional hypoglycemic treatment.Moreover,the western medicine group was given oral use of Atorvastatin Calcium Tablets,CM group was given Bushen Jianpi Recipe,and the combination group was given Atorvastatin Calcium Tablets together with Bushen Jianpi Recipe orally.The course of treatment lasted for 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,glucose and lipid metabolism indexes,fasting insulin(FINS),insulin resistance index(HOMA-IR)and serum ADP levels of the three groups were observed before and after the treatment.After treatment,the efficacy of TCM syndrome of the three groups was evaluated.Results(1)After 8 weeks of treatment,the total effective rates for TCM syndrome efficacy in the western medicine group,CM group,and combination group were 66.67%(20/30),90.00%(27/30),and 93.33%(28/30),respectively.The intergroup comparison showed that the TCM syndrome efficacy of the CM group and the combination group was significantly superior to that of the western medicine group(P＜0.05).(2)After treatment,the TCM syndrome scores in all of the three groups were decreased compared with those before treatment(P＜0.01),and the decreases of the scores in both CM group and combination group was superior to that in the western medicine group(P＜0.05 or P＜0.01).(3)After treatment,the levels of lipid metabolism parameters of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)in the three groups were improved to various degrees compared with the pre-treatment levels,of which the levels of TC,TG,and LDL-C were significantly decreased,and the level of HDL-C was significantly increased in comparison with that before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The intergroup comparison showed that the decrease of TC and LDL-C and the increase of HDL-C in the CM group were inferior to those in the western medicine group and the combination group(P＜0.05 or P＜0.01).(4)After treatment,the levels of glucose metabolism parameters of fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),glycated hemoglobin(HbA1c),FINS,and HOMA-IR in the CM group and the combination group were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),while only the levels of FPG,2hPG,and HOMA-IR in the western medicine group were decreased compared with those before treatment(P＜0.05 or P＜0.01).The intergroup comparison showed that the patients in the decrease of FPG,2hPG,HbA1c,FINS,and HOMA-IR levels in the CM group and the combination group was significantly superior to that in the western medicine group(P＜0.05 or P＜0.01).(5)In terms of adipokines,the serum ADP level in the three groups after treatment was significantly increased compared with that before treatment(P＜0.05 or P＜0.01),and the increase of serum ADP level in both CM group and combination group was significantly superior to that in the western medicine group(P＜0.05).Conclusion Bushen Jianpi Recipe has certain effect on regulating lipid metabolism,and has obvious advantages in improving clinical symptoms and insulin resistance,lowering blood glucose,and increasing ADP level in patients with T2DM complicated with dyslipidemia and differentiated as spleen-kidney deficiency type.

Objective: To analyze the prevalence of comorbidity of spinal curvature abnormality and malnutrition among primary and secondary school students aged 10-18 years in Tianjin in 2023, so as to provide scientific basis for the combined prevention of common diseases and multiple diseases among students and the construction of school health system. Methods: In September to October 2023, 31 884 primary and secondary school students aged 10 to 18 years in Tianjin were selected using stratified cluster random sampling. Abnormal spinal curvature in children and adolescents was assessed by Sereening of Spinal Curvature Abnormality of Children and Adolescents, while stunting, wasting, overweight, and obesity were determined according to the Screening for Malnutrition among Schoolage Children and Adolescents and Screening for Overweight and Obesity among Schoolage Children and Adolescents. The χ2 test was used to compare betweengroup differences in coprevalence, and multiple Logistic regression models were used to analyze the risk of different comorbidity types in different clusters. Results: The coprevalence of spinal curvature abnormality and malnutrition among primary and secondary school students in Tianjin was 1.6%, which was higher for girls than boys (1.8%, 1.4%), higher (2.5%) for senior high schools than for junior high schools and elementary schools (2.0%, 0.5%), and higher in rural than in urban areas (2.1%, 1.1%) (χ2=9.45, 141.92, 46.94, P<0.05). Multiple Logistic regression models showed that junior high school girls had a higher risk of incorrect posture comorbid with stunting and wasting (OR=4.52, 95%CI=1.84-11.06) and incorrect posture comorbid with overweight and obesity (OR=2.67, 95%CI=1.74-4.10) than boys, and that scoliosis/sagittal spinal abnormality comorbid with stunting and wasting (OR=0.10, 95%CI=0.02-0.44) risk was lower than that of boys, senior high school girls had a lower risk of scoliosis/sagittal spinal abnormality comorbid with overweight and obesity (OR=0.27, 95%CI=0.11-0.66) (P<0.05). Conclusions The coprevalence of spinal curvature abnormality and malnutrition is specific among primary and secondary school students in Tianjin, and the comorbidity type varies by gender and education stage. There is a need to increase prevention and control of spinal curvature abnormalities in school health working, intensive screening of key populations, and timely intervention.

Objective To investigate the effect and safety of common electric knife clamp coagulation technique in rabbit thyroidectomy.Methods According to the random number table method,12 New Zealand rabbits were divided into the clamp coagulation group and the ultrasonic scalpel group,with 6 rabbits in each group.The middle part of the thyroid gland in the clamp coagulation group was severed by common electric knife clamp coagulation,while that in the ultrasonic scalpel group was severed by ultrasonic scalpel electrocoagulation.The postoperative conditions of rabbits in the two groups were observ.The severed thyroid tissue was stained with hematoxylin-eosin(HE),and its histopathology after thermal damage was observed under the light microscope.The scope of thermal damage was determined.On the 1st,3rd and 7th day after operation,the auricular venous blood of all rabbits was collected to assess the serum interleukin-6(IL-6)and C-reactive protein(CRP)levels by enzyme-linked immunosorbent assay.The rabbits were killed on the 7th day after operation,and the residual thyroid glands were removed and stained by HE.The pathological changes and inflammatory cell infiltration were observed under the light microscope.Results The rabbits in the 2 groups survived well after operation,and the operative area healed well.No obvious effusion,blood clot,bleeding,incision infection or other complications were found in the residual cavity.Under the light microscope,the surface of the incisal margin of the thyroid gland showed obvious lesions.In the injured area,some cell structures were damaged with coagulated necrosis,some follicles were ruptured,and the contents inside were solidly concentrated and deeply stained.The cytoplasmic eosinophils in parafollicular cells increased,and nuclear pyknosis,fragmentation,and even dissolution occurred.The thermal damage ranges of thyroid tissues in the ultrasonic scalpel and clamp coagulation groups were(0.72± 0.10)mm and(0.88±0.11)mm,respectively.The range of thermal damage in the clamp coagulation group was significantly greater than that in the ultrasonic scalpel group(t=-2.740,P＜0.05).On the 1st,3rd and 7th day after surgery,there was no significant difference in the levels of serum CRP and IL-6 between the two groups(P＞0.05).The serum IL-6 levels in both groups on the 3rd and 7th day after surgery were significantly higher than those on the 1st day after surgery(P＜0.05).There was no significant difference in serum IL-6 level on the 3rd and 7rd day after surgery in the two groups(P＞0.05).Thyroid follicular atrophy,glia reduction,follicular epithelial hyperplasia,collagenization and hyperplasia of interstitial fibers were observed in the residual thyroid sections of both groups.No obvious inflammatory cell infiltration was observed.Conclusion In rabbit thyroidectomy,it is safe to remove the thyroid gland using the common electric knife clamp coagulation technique.In terms of preventing thermal damage,the ultrasonic scalpel is better than the common electric knife clamp coagulation technique,but the thermal damage to thyroid tissues caused by the common electric knife clamp coagulation technique is within the safe operating range.

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.

Carbapenem-resistant Enterobacteriaceae bacteria are widespread worldwide,with carbapenem-resistant Klebsiella pneumoniae being the most obvious,and these bacteria are usually resistant to clinically used antibiotics.In the context of the limited development and application of new drugs,and the unclear effica-cy of combination therapy,this article analyzes the relevant literature on the prevention,single and combina-tion therapy of carbapenem-resistant Klebsiella pneumoniae infection,and delays the occurrence of drug resist-ance through the linkage of prevention and anti-infective therapy in the case of carbapenemase epidemic and increasing antibiotic resistance,so as to provide a new strategy for preventing the spread of drug-resistant bac-teria and anti-infective therapy.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To investigate the effect of epidermal growth factor tyrosine kinase inhibitor AG1478 combined with oxaliplatin(OXA)on non-small cell lung cancer cells H1299.Methods H1299 cells were divided into control group(conventional culture,without drug),OXA-25,-50,-100 groups(25,50 and 100 μmol·L-1 OXA),AG-20 group(20 μmol·L-1AG1478)and OXA+AG group(25 μmol·L-1 OXA and 20 μmol·L-1AG1478).Detection of cell survival rate by MTT assay and calculation of half inhibitory concentration(IC50).Reactive oxygen species(ROS)probe H2DCFDA was used to detect ROS levels.Autophagy of H1299 cells was detected by MDC method.Western blot was used to detect the expression levels of phosphorylated-phosphoinositide 3-kinase(p-PI3 K),phosphorylated-protein kinase B(p-AKT),autophagy protein(Beclin-1)and microtubule associated protein light chain 3-Ⅱ(LC3-Ⅱ).Results The IC50 of OXA on H1299 cells was 91.09 μmol·L-1.The IC50 of AG1478 on H1299 cells was 31.83 μmol·L-1.The relative ROS level were 1.00±0.03,1.15±0.02,1.76±0.04,2.89±0.02,1.05±0.01 and 3.20±0.03,respectively;the relative MDC levels were 1.00±0.04,1.10±0.02,1.16±0.02,1.46±0.04,1.04±0.01 and 1.31±0.02,respectively;the relative expression levels of p-PI3K protein were 1.12±0.05,0.88±0.06,0.72±0.07,0.60±0.05,0.91±0.07 and 0.64±0.09,respectively;the relative expression levels of p-AKT protein were 1.09±0.04,0.87±0.08,0.77±0.07,0.63±0.05,0.76±0.05 and 0.46±0.03,respectively;the relative expression levels of Beclin-1 protein were 0.82±0.03,0.91±0.04,1.06±0.28,1.11±0.03,0.87±0.04 and 1.27±0.10,respectively;the relative expression levels of LC3-Ⅱ protein were 0.65±0.08,0.82±0.11,1.08±0.12,1.38±0.09,0.72±0.11 and 1.38±0.15,respectively.Compared the OXA+AG group and the OXA single group with the control group,compared the OXA+AG group with the OXA single group,there were statistically significant differences in the above indicators(P＜0.05,P＜0.01).Conclusion AG1478 combined with OXA can increase ROS levels in non-small cell lung cancer cells H1299 and inhibit the activation of PI3K signaling pathway,thus inducing autophagy.