OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To analyze the clinical features and surgical treatment strategies of T4a thyroid cancer.Methods We retrospectively analyzed patients with thyroid cancer treated in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from January 2004 to May 2021.A total of 303 cases were included and statistically analyzed for pathological type,invaded organs,surgical approach,survival time,and overall survival rate.The postoperative survival curves of the patients were analyzed using the Kaplan Meier method.Results Of the 303 patients enrolled,53 patients were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 98.4％(246/250),97.0％(224/231)and 90.2％(92/102),respectively.Of the 94 patients with recurrent laryngeal nerve invasion only,13 were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 100％(81/81),98.7％(77/78)and 97.4％(38/39),respectively.There were 151 patients with invasion of recurrent laryngeal nerve and tracheal/laryngeal/esophageal nerve,31 of them were lost to follow-up,and the 1-year,3-year and 5-year overall survival rates were 96.7％(116/120),95.3％(101/106)and 82.2％(37/45),respectively.According to the survival curve analysis,the group with recurrent laryngeal nerve invasion only had an advantage in overall survival time over the group with recurrent laryngeal nerve and tracheal/laryngeal/esophageal invasion.Conclusion Surgical resection is supposed to be preferred for T4a thyroid cancer if there is a chance of surgery.A reasonable surgical strategy,radical surgery while preserving the vital tissues and organs,and one-stage repair and reconstruction can bring patients a better quality of life and prognosis.

Objective To observe the effects of different frequencies of electroacupuncture on the degree of atrophy of quadriceps femoris in rabbits with anterior cruciate ligament(ACL)injury model;To explore the possible mechanisms of electroacupuncture in treating ACL injury.Methods Totally 24 New Zealand rabbits were randomly divided into blank group,model group,low-frequency electroacupuncture group and high-frequency electroacupuncture group,with 6 rabbits in each group.Except for the blank group,ACL injury models were established in the other groups.On the 7th day after modeling,the low-frequency electroacupuncture group and the high-frequency electroacupuncture group performed electroacupuncture treatment(continuous wave,frequency of 2 Hz and 100 Hz respectively,and left the needle in place for 20 min)at"Xuehai"and"Liangqiu"of the operation side,and the remaining groups were only grasped and immobilized,for 21 days.The mass ratio of the quadriceps femoris was calculated,the histopathological morphology of the quadriceps femoris tissue of the rabbits in each group was observed by HE staining,the expressions of NO,iNOS in quadriceps femoris tissue were detected by ELISA,the content of ROS in quadriceps femoris tissue was detected by fluorescent probe,the protein expressions of PERK,ATF6,IRE1,MuRF1,MAFbx in quadriceps femoris tissue were detected by Western blot.Results Compared with the blank group,the quadriceps femoris muscle mass ratio of the model group rabbits was significantly reduced(P<0.01),with irregular arrangement of muscle cells,accompanied by swelling and atrophy,significant interstitial edema,and extensive inflammatory infiltration,the contents of NO,iNOS and ROS in quadriceps femoris tissue significantly increased(P<0.01),while the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly increased(P<0.01).Compared with the model group,the quadriceps femoris muscle mass ratio in the low-frequency and high-frequency electroacupuncture groups significantly increased(P<0.01),with regular arrangement of muscle cells,improved swelling and atrophy of cells,and reduced interstitial edema and inflammation,the contents of NO,iNOS and ROS in quadriceps femoris tissue were significantly reduced(P<0.01),and the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly decreased(P<0.01).Moreover,the low-frequency electroacupuncture group had better effects than the high-frequency electroacupuncture group(P<0.05).Conclusion Different frequencies of electroacupuncture intervention in ACL injury rabbits can better delay the degree of quadriceps femoris atrophy,and its mechanism may be related to reducing the expressions of oxidative metabolites NO,iNOS,ROS,and reducing the expressions of endoplasmic reticulum stress-related proteins PERK,ATF6,IRE1 in quadriceps fermoris,which in turn inhibit the expressions of quadriceps atrophy factors MuRF1,MAFbx,and delaying the degradation of quadriceps muscle proteins.The effect of low-frequency electroacupuncture is superior to the high-frequency electroacupuncture.

Humans ; Asthma/drug therapy* ; Biological Therapy

OBJECTIVE To analyze the influential factors for dose-corrected trough concentration （C/D） of amisulpride， and to provide reference for rational use of it in clinic. METHODS The results of the last serum concentration monitoring and relevant medical data of schizophrenic inpatients who were monitored for the treatment of amisulpride in the Mental Health Center of the First Hospital of Hebei Medical University from March to November 2021 were collected retrospectively and analyzed the effects of age， sex， body mass index （BMI）， serum creatinine level， and combined medication on the C/D value of amisulpride. RESULTS A total of 133 schizophrenic inpatients were included， and median dose of amisulpride was 600.00 mg/d， median serum concentration was 332.57 ng/mL， and median value of C/D was 0.61 ng·d/（mL·mg）. The serum concentration of 49 patients was within the recommended range of relevant guideline （100-320 ng/mL）， and 27 patients exceeded the laboratory warning concentration （640 ng/mL）. There was no statistical significance in drug dose， serum concentration or C/D value among the patients of different genders （P＞0.05）. The serum concentration of minor patients was significantly lower than that of adult patients （P＜0.05）， but there was no statistical significance in drug dose or C/D value between minor patients and adult patients （P＞0.05）. The C/D value of amisulpride in obese patients （BMI＞28 kg/m2） was significantly lower than that in normal patients （BMI 18.5- 23.9 kg/m2）； the combination of olanzapine， sodium valproate and benzodiazepines did not affect the C/D value of amisulpride （P＞0.05）； the level of serum creatinine in patients was not related to the dose of amisulpride （r＝0.081， P＞0.05）， but was positively related to the C/D value of the drug （r＝0.285， P＜0.05）. CONCLUSIONS The age， BMI and serum creatinine level of patients are closely related to the C/D value of amisulpride. In the clinical treatment of schizophrenia with amisulpride， we should fully consider the patient’s age， body mass， serum creatinine and other factors， and develop a personalized drug regimen for patients to ensure the safety and effectiveness of treatment.

【Objective】 To investigate the related factors of allogeneic blood transfusion (ALBT) in total hip arthroplasty. 【Methods】 Thebasic information, surgical details and laboratory data of 258 patients who underwent total hip arthroplasty in Orthopedics Department of our hospital were collectedfrom the electronic medical record system and laboratorytest system. The factors concerningALBT were obtainedby single factor and multivariate logistic regression analysis. 【Results】 The ALBT rate in this study was 19%, and the differencesin such important factors affecting ALBT as gender, age, intraoperative blood loss, drainage volume, operation duration, preoperative hemoglobin (Hb), preoperative activated partial thromboplastin time (APTT), preoperative prothrombin time (PT) andhypertension between the two groupswere notable (P<0.05). Multivariate regression analysisrevealed that the independent related factors ofALBT were age ≥ 60 years (OR3.577), intraoperative blood loss (OR1.003), drainage volume (OR1.004)and preoperative PT (OR1.888). Preoperative Hb (OR0.94) was a protective factor. 【Conclusion】 Specific and individualized evaluation of ALBT, aimed atreducingunnecessary blood transfusion, can be provided through the analysis of relevant factors.

Objective:To discuss strategies in treatment of poorly differentiated thyroid carcinoma (PDTC) .Methods:Clinical data of 31 cases with PDTC were reviewed retrospectively, who were treated in Department of Head & Neck Surgery, Sichuan Cancer Hospital & Institute by primary surgical resection with or without adjuvant therapy. 27 cases had total thyroidectomy compounded neck dissection or extened total thyroidectomy when trachea or esophagus involved. 4 cases underwent partial resection of tumor. 11 cases were treated with external beam radiotherapy (EBRT) after surgery, 10 cases were treated with postoperative radioiodine, and 8 cases had chemotherapy.Results:The median follow-up time was 18 months (ranged from 3-96 months) . 19 patients died of local recurrence or distant metastasis. Kaplan-Meier analysis and Log-rank analysis was used to compare the differences between groups. Five-year survival was 35.9%. Compared to the cases with partial resection, the cases with surgical disease clearance had longer survival ( P=0.00) . The same statistical difference was found between patients with or without radioiodine ( P=0.017) . The patients treated with radioiodine had longer survival. No statistical differences were found among patients with or without chemotherapy or EBRT. COX regression analysis showed stage of tumor ( P=0.005) , total resection ( P=0.006) and postoperative radioiodine ( P=0.013) were same to predict longer survival. Conclusions:Thorough resection of tumor is the most important therapy for PDTC. Postoperative radioiodine is recommended for patients with high recurrence risk. EBRT is recommended to control local unresectable PDTC.

Objective: To explore the advantages and clinical efficacy of free chimeric perforator flap based on the descending branch of circumflex femoral artery applied to tongue reconstruction after advanced tongue cancer resection. Methods: From October 2013 to December 2018, 57 cases received tongue and oral base reconstruction surgeries using the descending branch of circumflex femoral artery chimeric perforator flap, including 39 males and 18 females, ranged from 20 to 76 years old. And all cases were with stage T3 and T4 tongue cancers, including 35 cases of squamous cell carcinoma, 7 cases of low differentiation cancer, 5 cases of oncosarcoma, and 10 cases of adenoid cystic carcinoma. The tongue was reconstructed by using perforator flap and muscle flap to fill the dead space at the oral floor. The artery anastomoses with the superior thyroid artery or facial artery in the receiving area, and the vein anastomoses with the internal jugular vein in the receiving area. The shape, function and local complications of the reconstructed tongue were observed after operation. Results: Of 57 cases, only one case had partial necrosis of flap, while other 56 cases with chimeric perforator flap survived. Postoperative gastric tube and tracheal cannula were removed in all patients, no cases with oral fistula. All donor sites were sutured in one stage. Postoperative radiotherapy was performed in 41 of the patients. All patients were followed up for 3 to 60 months (average of 20.7 months), with satisfactory esthetic and functional results in reconstructed tongues. Only linear scars were left in the donor areas of the legs, and no lower limb dysfunction was observed. Conclusions The descending branch of circumflex femoral artery chimeric perforator flap can used for repairing simultaneously the defects of both tongue and oral base. It is helpful to avoid the occurrence of oral fistula and to provide the reconstructed tongue with a good function. It is a good choice to use the descending branch of circumflex femoral artery chimeric perforator flap for tongue reconstruction after resection of advanced tongue cancer resection.

The discovery of hydroxylases in the anticancer drug taxol biosynthesis pathway is a hotspot and difficulty in current research. In this study, a new hydroxylase gene TcCYP725A22 (GenBank accession number: MF448646.1) was used to construct a sub-cellular localization vector pCAMIBA1303-TcCYP725A22-EGFP to get the transient expression in onion epidermal cells. Laser confocal microscopy revealed that the protein encoded by this gene was localized in the cell membrane. Furthermore, the recombinant plant expression plasmid pBI121-TcCYP725A22 was constructed. After transient transformation to the Taxus chinensis mediated by Agrobacterium tumefaciens LBA4404, qRT-PCR and LC-MS were utilized to analyze the effects of TcCYP725A22 overexpression on the synthesis of taxol. The results showed that, in the TcCYP725A22 overexpressed cell line, expression levels of most defined hydroxylase genes for taxol biosynthesis were increased, and the yield of taxanes were also increased. It was concluded that the hydroxylase gene TcCYP725A22 is likely involved in the biosynthetic pathway of taxol.
Biosynthetic Pathways ; Mixed Function Oxygenases ; Paclitaxel ; Taxoids ; Taxus