OBJECTIVE To explore the significance of pharmaceutical care through the diagnosis and treatment of a patient with exogenous insulin autoimmune syndrome （EIAS）， combined with the analysis of literature reports. METHODS Clinical pharmacist participated in the diagnosis and treatment process of one case of EIAS. Based on the characteristics of the patient’s condition， the pharmacist provided medication suggestions and formulated pharmaceutical monitoring measures. At the same time， the pharmacist searched for relevant literature on insulin autoimmune syndrome （IAS） and EIAS， extracted data （gender， age， occurrence time， laboratory tests， clinical symptoms， intervention and outcome）， and conducted analysis. RESULTS Based on the patient’s medication information in the past 3 years， clinical pharmacist determined that the EIAS was likely caused by insulin aspartate 30. The clinician adopted the clinical pharmacist’s suggestion to discontinue insulin and switch to oral hypoglycemic drugs. The patient improved after treatment. The literature analysis showed that among the 257 patients with IAS reported， 212 cases were caused by drugs； among them， 23 cases were caused by lipoic acid， and 56 cases were caused by exogenous insulin. There were no significant differences in age， glycosylated hemoglobin， and body mass index between the two groups. The lowest blood glucose level in the lipoic acid group was significantly lower than that in the exogenous insulin group （P＜0.05）. The proportion of females and the proportion of fasting insulin ≥ 1 000 μU/mL were significantly higher in the lipoic acid group than in the exogenous insulin group （P＜0.05）. CONCLUSIONS Compared with EIAS， lipoic acid-induced IAS usually causes more severe hypoglycemia， and the fasting insulin level is usually higher than 1 000 μU/mL， which is more common in female patients. The participation of clinical pharmacists in the diagnosis and treatment of EIAS can help improve the diagnosis and treatment level of similar rare diseases and ensure the safety of patients’ medication.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan （RN12）" "Tianshu （ST25）" and "Shangjuxu （ST37）" on the colon tissue of mice with ulcerative colitis （UC）， and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group， model group， moxibustion group and mesalazine group， with 10 mice in each group. In all the groups except for the blank group， UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling， the moxibustion group was treated with grain-sized moxibustion at Zhongwan， Tianshu and Shangjuxu ， 3 cones per acupoint， 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed， and the disease activity index （DAI） score was evaluated. The colon length， intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3） and suppressor of cytokine signaling 3 （SOCS3） in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry， respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group， the mice in the model group had unclean perianal area， unformed stool， destroyed colonic mucosal morphology， shortened body weight and colon length， increased DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels， increased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and decreased mRNA and protein expression of SOCS3 （P＜0.01）. Compared to those in the model group， the perianal area of mice in the moxibustion group and the mesalazine group was improved， and the colonic mucosal morphology was more complete； body weight and colon length increased， while DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels decreased， with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and increased SOCS3 mRNA and protein expression （ P＜0.01 or P＜0.05 ）. There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan"， "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice， and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.

Objective:To explore the clinical efficacy of cenegermin in the treatment of neurotrophic keratitis (NK).Methods:An observational case series study was adopted.Twenty-two patients (26 eyes) with moderate and severe NK diagnosed in Xi'an No.1 Hospital from June to November 2021 were collected and locally treated with cenegermin eye drop.After the corneal epithelium of the affected eye healed, the treatment ended.Relevant index data of patients before and after treatment were obtained through eye examination.The main indicators were the fiber length of corneal sensation measured by Cochet-Bonnet aesthesiometer, the morphological and quantitative indexes of corneal nerves by in vivo confocal microscopy, including the density of corneal nerve fibers and the number of nerve bifurcation points, and tear meniscus height measured by Keratograph Ocular Surface Analyzer.The secondary indicators were best corrected visual acuity (BCVA) and adverse reactions.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xi'an No.1 Hospital (No.2021-11). Written informed consent was obtained from each subject. Results:The average treatment duration of patients receiving cenegermin was (4.42±1.86) weeks.After treatment, the corneal epithelial defect of moderate and severe patients healed completely.After treatment, the fiber length of sensation of corneal epithelial defect area and superior defect area were improved, the differences were statistically significant ( Z=-2.45, -3.22; both at P<0.05). There was no significant difference in corneal sensation in inferior, nasal and temporal of corneal epithelial defect area between before and after treatment ( Z=-1.89, -0.31, -1.86; all at P>0.05). After treatment, the average corneal nerve fiber density and the number of corneal nerve fiber bifurcation points in the affected eyes were significantly increased ( Z=-3.95, -3.48; both at P<0.01). There was no significant difference in the tear meniscus height between before and after treatment ( Z=-1.58, P=0.11). After treatment, the BCVA (LogMAR) of patients was 0.22(0.10, 0.40), which was higher than 0.52(0.30, 0.70) at baseline, and the difference was statistically significant ( Z=-3.63, P<0.01). During the treatment of cenegermin eye drops, transient pain occurred in 3 eyes, and intraocular pressure increased in 1 eye, which all returned to normal after symptomatic treatment. Conclusions:Topical application of cenegermin can repair corneal nerve morphology and function in patients with NK.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Objective To investigate the clinical efficacy and safety of Zishen Jianpi Quyu Formula in treating patients with migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.Methods A total of 104 patients with migraine without aura of kidney deficiency and blood stasis type were randomly divided into the control group and the trial group,with 52 cases in each group.The control group was treated with Flunarizine Hydrochloride Capsules,and the trial group was treated with Zishen Jianpi Quyu Formula on the basis of treatment for the control group.One menstrual cycle constituted a course of treatment,and the treatment covered a total of two courses(eight weeks).The changes of traditional Chinese medicine(TCM)syndrome score,migraine attack frequency,duration of migraine headaches,visual analogue scale(VAS)score of migraine headache intensity,Headache Impact Test-6(HIT-6)score and hemorheology indexes in the two groups before and after treatment were observed.Moreover,the efficacy for TCM syndrome and clinical safety in the two groups were evaluated.Results(1)After two courses of treatment,the total effective rate of the trial group was 90.38%(47/52),and that of the control group was 69.23%(36/52),the intergroup comparison(by chi-square test)showed that the efficacy for TCM syndrome in the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores of the patients in both groups were significantly lower than those before treatment(P＜0.05),and the reduction of TCM syndrome score in the trial group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the migraine attack frequency,duration of migraine headaches,VAS scores of migraine headache intensity in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the improvement of migraine headache parameters in the trial group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the HIT-6 score in the two groups was decreased significantly compared with those before treatment(P＜0.05),and the decrease of HIT-6 score in the trial group was significantly superior to that in the control group(P＜0.05).(5)After treatment,hemorheology indexes(including plasma viscosity,whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,and hematocrit)in the two groups were improved compared with those before treatment(P＜0.05),and the improvement of each of hemorheology indexes in the trial group was significantly superior to that in the control group(P＜0.05).(6)During treatment,no serious adverse events occurred in the two groups,which was of high safety.Conclusion Zishen Jianpi Quyu Formula exerts remarkable clinical efficacy in treating patients of migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.The formula is effective on improving the TCM syndromes and migraine attacks of the patients,achieving the efficacy of milder headache,lower attack frequency and shorter duration,more stability hemorheology indexes and higher safety.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective To prepare Zishen pills as gel plaster according to the prescription,and investigate its transdermal absorption characteristics in vitro.Methods Based on preliminary experiments,the matrix prescription of the gel plaster was optimized by single-factor tests and the Box-Behnken design.Evaluation indicators included initial viscosity,viscosity retention and sensory scores.The modified Franz diffusion cell was used to investigate the effect of penetration enhancers on the transdermal characteristics of gel plaster in vitro,with the permeability of neomangiferin,phellodendrine hydrochloride,mangiferin and berberine hydrochloride as evaluation indicators.Results The prescription dosage of the preferred matrix for the Zishen gel plaster was sodium polyacrylate NP700 2.55 g,glycerin 11.04 g,polyvinylpyrrolidone K90 1.13 g,tartaric acid 0.1 g,glycyrrhizin 0.1 g,kaolin 0.3 g,and distilled water 15 g.Among different types and concentrations of permeation enhancers,5%aminoketone showed the best permeation performance.The permeation rates for neomangiferin,phellodendrine hydrochloride,mangiferin,and berberine hydrochloride were 1.5338,1.7809,2.3247 and 20.0899 μg·(cm2)-1·h-1,and the penetration rates were 2.4319,1.9408,1.9604 and 1.4701,respectively.The percutaneous absorption curve of the drug conformed to the zero-order kinetic equation.Conclusion The preparation process of the obtained gel plaste is stable and feasible,with good adhesive properties,sustained drug release,and favorable in vitro percutaneous permeability,indicating potential clinical application value.

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.