Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

Invasive fungal disease （IFD） is a deep infectious disease with an overall increasing incidence in patients with hematologic malignancies. Triazoles， polyenes， echinocandins echinocandin antifungal drugs， 5-fluorocytosine and Compound sulfamethoxazole are the main drugs used in the clinical treatment of IFD. Therapeutic drug monitoring for IFD prevention and treatment is helpful to optimize treatment outcomes and reduce adverse effects. In this paper， the effective plasma concentration ranges of the above 5 types of drugs are systematically summarized， and the correlation between the plasma concentration of antifungal drugs and the efficacy and adverse reactions is reviewed. Solid phase extraction combined with ultra-performance chromatography-tandem mass spectrometry is a promising detection method in this research field.

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

OBJECTIVE To extract the effective components of Psoralea corylifolia and evaluate its efficacy in the treatment of vitiligo. METHODS The concentrations of psoralen， isopsoralen， neobavaisoflavone， corylin， psoralidin， corylifolinin， and bakuchiol in P. corylifolia extract were determined by ultra-performance liquid chromatography. Based on the analytic hierarchy process （AHP） and Plackett-Burman design， with the concentrations of the 7 components as evaluation indexes and the crushing degree， ethanol concentration， and soaking time as factors， the extraction process of P. corylifolia was optimized by Box-Behnken response surface methodology and the validation test was conducted. Zebrafish were divided into blank control group， positive control group （8-methoxypsoralen， 10.8 μg/mL）， and low-， medium-， and high-concentration groups of P. corylifolia extract （500， 1 000， 2 000 μg/mL）， with 6 fish in each group. The effects of P. corylifolia extract on the melanin production of zebrafish were studied by density analysis. RESULTS The best extraction process was P. corylifolia powder over 60 meshes and soaked in 80% ethanol for 72 hours. The average comprehensive score of three validation experiments was 98.27， with an RSD of 1.36%， and the relative error was 1.02% compared with the predicted value of the fitting equation （97.28）. Compared with the blank control group， the melanin pigmentation of zebrafish in the low-， medium-， and high-concentration groups of P. corylifolia extract was significantly increased （P＜0.01）. CONCLUSIONS The optimized extraction process of P. corylifolia is reasonable and feasible， and the obtained P. corylifolia extract can significantly promote the production of melanin in zebrafish.

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.

OBJECTIVE：To study the effects of rat intestinal flora on the pharmacokinetic parameters of pyrazinamide and its active metabolite pyrazinoic acid. METHODS ：Totally 16 SD rats were randomly divided into trial group and control group ，with 8 rats in each group. Trial group was given mixed antibiotics （streptomycin sulfate+neomycin sulfate ）intragastrically to construct pseudoaseptic rat model. After modeling ，both groups were given pyrazinamide intragastrically （150 mg/kg）. Before and 0.167， 0.333，0.667，1，1.5，2，3，4，6，9 h after administration ，0.1 mL blood sample was collected from orbital venous plexus ，and 0.3 mL blood sample was collected from orbital venous plexus 12，24 h after administration. Using phenacetin as internal standard ， LC-MS/MS method was adopted to determine the plasma concentration of pyrazinamide and pyrazinoic acid. The determination was performed on Agilent ZORBAX SB-Aq column with mobile phase consisted of 0.2％ formic acid （containing 8 mmol/L ammonium acetate）-methanol（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 30 ℃，and sample size was 10 μL. The ion source was ESI and the temperature of ion source was 500 ℃. The collision gas was nitrogen and the pressure was 10 psi. The temperature of mass transfer interface was 100 ℃. The mass spectrum monitoring mode was multi reaction monitoring ， and the collection mode was positive ion mode. The monitoring transition ion-pairs were m/z 124.0→79.0（pyrazinamide），m/z 125.1→79.1（pyrazinic acid ）and m/z 180.0→110.2（internal standard ）. The de-clustering potential and collision voltage were 55， 26 and 85 V，24，23 and 28 V，respectively. The pharmacokinetic parameters were calculated and compared by using DAS 2.1.1 software. RESULTS ：The linear ranges of pyrazinamide and pyrazinoic acid were 25-5 000 ng/mL（r＝0.997 6）and 100-12 500 ng/mL（r＝0.999 0）. The lower limits of quantification were 25 and 100 ng/mL，respectively. Intra-batch and inter-batch accuracy were 92.93％-100.50％，and RSDs of intra-batch and inter-batch precision and matrix effect tests were all lower than or equal to 8.42％（n＝6 or n＝3）. Compared with control group ，tmax of pyrazinamide in trial group was prolonged significantly （P＜0.01）； there was no statistical significance in other pharmacokinetic parameters between 2 groups（P＞0.05）. CONCLUSIONS ：The absorption of single dose pyrazinamide is delayed with the change of intestinal flora in rats.

OBJECTIVE：To analyze the mass spectrometry fragmentation regularity of bicyclol ，bifendate and schisandrin C ， and to identify the impurities of bicyclol raw material. METHODS ：UHPLC-ESI-Q-TOF-MS method was adopted. Using electrospray ionization source ，in positive ion mode ，the excimer ion and characteristic fragments of bicyclol ，bifendate and schisandrin C were analyzed by means of TOF-MS. According to the mass change of fragments ，the possible fragmentation pathways were speculated ，and the fragmentation regularity were analyzed and summarized. Bicyclol raw material sample was first separated by liquid chromatography to find the impurity peaks in it ，and then the impurity peaks were analyzed by mass spectrometer；the impurity identification was conducted by combining with the fragmentation regularity. RESULTS ：The 3 compounds all produced [M+H] + excimer ion in the positive ion mode. After collision-induced dissociation ，the C-O bond ，the simple rupture of the C-C bond and the ring-opening cleavage of the oxygen ring occurred ；with the loss of neutral fragments ， mainly CH 2O，supplemented by CO 2，CO and CHO ，the dissociation was concentrated in the middle and high quality regions. C-C and C-O bonds of 3 compounds were simply broken only in the branched chain structure and/or oxygen ring structure ，but the structure of the biphenyl parent nucleus remained unchanged. Among them ，the bicyclol contained a benzyl alcohol structure ，so under acidic mobile phase conditions ，it would exist stably in the form of [M+H －H2O]+. Because schisandrin C contained 8-membered ring structure，ring opening first occurred under collision voltage ，and then neutral fragment loss occurred. The secondary mass spectra of impurity in bicyclol raw material were consistent with the mass spectra fragmentation of secondary fragments of bifendate. CONCLUSIONS：The study summarized mass spectrometry fragmentation regularity of 3 schisandrin derivatives. The impurity in bicyclol raw material may be bifendate.

Objective:To review our clinical experience on total pancreatectomy in treatment of pancreatic diseases.Methods:The clinical data of 25 patients with pancreatic diseases who underwent total pancreatectomy at Nanjing Drum Tower Hospital from February 2016 to October 2019 were retrospectively analyzed. The data on general information, surgical methods, postoperative complications, changes in postoperative pancreatic endocrine and exocrine functions and quality of life were analyzed.Results:There were 16 males and 9 females, aged (60.9±9.4) years. Planned selective surgery was carried out in 16 patients while unplanned operations in 9 patients. There were 15 patients with pancreatic neoplasms with 4 patients who received neoadjuvant or conversion therapy, 6 patients with intraductal papillary mucinous neoplasms, 3 patients with chronic pancreatitis and 1 patient with pancreatic neuroendocrine carcinoma. The total postoperative complication rate was 36% (9/25). One patient died in the perioperative period, and one patient underwent a second operation. After 6 months of operation, 2 of 24 patients had died. The remaining patients had a fasting blood sugar of (8.9±1.6) mmol/L, with an insulin dosage of (30.7±10.6) U/d. The average dosage of trypsin was (1.1±0.3) g/d. The quality of life score reached or exceeded the preoperative levels.Conclusions:Total pancreatectomy was safe and feasible for some pancreatic diseases. For patients with pancreatic cancer, its long-term oncological outcomes need further studies.

Objective:To investigate the influencing factors for pancreatic endocrine and exocrine insufficiency after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinicopathological data of 168 patients who underwent pancreaticoduodenectomy in the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2017 were collected. There were 96 males and 72 females, aged (64±13)years, with a range from 38 to 75 years. Of the 168 patients, 36 had pancreatic endocrine insufficiency while 8 had pancreatic exocrine insufficiency preoperatively. All patients underwent pancreaticoduodenectomy. Observation indications: (1) surgical situations and follow-up; (2) analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy; (3) analysis of influencing factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Follow-up using out-patient examination and telephone interview was performed to detect postoperative condition of blood glucose control, diet and nutrition, tumor recurrence and metastasis up to June 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Surgical situations and follow-up: all the 168 patients underwent pancreaticoduodenectomy successfully and recovered well after operation. All patients were followed up for 6 months. The level of fasting and postprandial blood glucose of the 168 patients after surgery were 7 mmol/L(range, 5-9 mmol/L) and 10 mmol/L(range, 7-14 mmol/L), respectively. The defecation frequency was (2.4±1.2)times per day. No tumor recurrence or metastasis occurred in either patient. One hundred and thirty-two of the 168 patients were included in the study excepting patients with pancreatic endocrine insufficiency before operation. At postoperative 6 months, 47 patients developed pancreatic endocrine insufficiency, with an incidence of 35.61%(47/132). One hundred and sixty of the 168 patients were included in the study excepting patients with pancreatic exocrine insufficiency before operation. At postoperative 6 months, 68 patients had pancreatic exocrine insufficiency, with an incidence rate of 42.50%(68/160). (2) Analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that gender, metabolic syndrome, chronic pancreatitis, excision point, and postoperative chemotherapy were the related factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy ( χ2=5.300, 6.270, 4.473, 4.392, 5.397, P<0.05). Results of multivariate analysis revealed that male and metabolic syndrome were independent risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy [ hazard ratio ( HR)=5.252, 5.364, 95% confidence interval ( CI): 1.362-6.382, 1.891-12.592, P<0.05)]. (3) Analysis of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that body mass index (BMI), chronic pancreatitis, total bilirubin, excision point, postoperative pancreatic fistula as grade B or C, and pancreatic fibrosis were related factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( χ2=1.691, 4.910, 7.763, 5.605, 4.663, 7.700, P<0.05). Results of multivariate analysis showed that BMI<18.5 kg/m 2, chronic pancreatitis, total bilirubin ≥171 μmol/L were independent risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( HR=3.695, 5.231, 7.623, 95% CI: 1.232-7.324, 2.161-6.893, 1.562-5.235, P<0.05). Conclusions:Male and metabolic syndrome are risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. BMI<18.5 kg/m 2, chronic pancreatitis, and total bilirubin ≥171 μmol/L are risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy.

Objective: To evaluate an assay permitting amplification of target 5′-untranslated region (5′-UTR) sequences directly from clinical specimens and distinction among serotypes of enterovirus (EV). Methods: A total of 518 rectal swabs and 148 nasal swabs tested positive by pan-enterovirus real-time PCR were collected. 5′-UTR and the viral protein 1 (VP1) gene fragments were amplified and sequenced separately for serotyping. The inconsistent samples by 5′-UTR and VP1 serotyping were further determined by using the serotype-specific RT-PCR. Results: A total of 553 (83.0%) samples were detected by 5′-UTR serotyping and 318 (47.7%) were detected by VP1 serotyping in all 666 positive specimens, and there was significant difference in the detection rates between two methods in rectal and nasal swabs (P<0.001). For the rectal swabs, the mainly detected serotypes were CoxA6 (217), CoxA16 (88), EVA71 (40), CoxA10 (28) and CoxA4 (27) by 5′-UTR serotyping. Compared with the VP1 serotyping, the sensitivity and specificity of 5′-UTR serotyping were 57.1%-100% and 67.4%-98.1% respectively, with varied consistence with serotypes (kappa value 0.214-0.283). For the nasal swabs, the most frequently detected serotype was EVD68, with the sensitivity of 100%, the specificity of 91.1%, and the poor consistence (kappa value 0.217). CoxA6, CoxA16, EVA71, CoxA10 and EVD68 were further confirmed by serotype-specific RT-PCR. Using VP1 serotyping combined with serotype-specific RT-PCR as a reference method , the effect of performance of 5′-UTR serotyping on diagnosis was increased. Conclusions The performances of 5′-UTR serotyping in enterovirus vary with serotypes. The application of 5′-UTR serotyping should be considered comprehensively according to the purpose of the study.