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.

Objective To screen long non-coding RNA(lncRNA)associated with disulfidptosis and investigate the immune landscape between lncRNA and pancreatic cancer,for effective guidance in clinical practice.Methods The normal and pancreatic cancer tissue samples were obtained from The Cancer Genome Atlas database,and the lncRNA associated with disulfidptosis was identified based on the Cox and LASSO regression analyses.A risk prognosis model was constructed,and its predictive performance was verified using comprehensive methods.An accurate nomogram was construted to predict the prognosis of patients with pancreatic cancer.The biological differences were analyzed via Gene Ontology,Gene Set Enrichment Analysis,and an immunoassay.The immunotherapy response was estimated using the tumor mutational burden(TMB)score.Results A total of 251 disulfidptosis-related lncRNAs were successfully identified,and three groups of lncRNAs were selected as the reference for the risk model.Pathway analysis showed that immune-related pathways were associated with disulfidptosis-related lncRNA risk models.The risk score was significantly correlated with immune cell infiltration and the ESTIMATE score.Patients with higher risk scores had elevated TMB,indicating that high-risk patients exhibited a better immune checkpoint blockade response.Conclusion The findings of this study contribute to a deeper understanding of disulfidpto-sis-related lncRNA and provide a potential therapeutic strategy for pancreatic cancer.

Objective To explore the role of an artificial intelligence(AI)model based on real-time object detection network in fetal facial ultrasound examination.Methods With the normal fetal facial ultrasound standard plane(FFUSP)at 20-24 weeks of gestation as the research object,a FFUSP recognition model based on real-time object detection network was constructed.The recognition accuracy of the model for FFUSP and the anatomical structures were analyzed,and the clinical value was evaluated by analyzing its performance in identifying FFUSP in 119 cases of fetal ultrasound images.Results The overall precision,recall rate,mAP@.5 and mAP@.5:.95 of the AI model were 97.8%,98.5%,98.1%and 61.0%,respectively.The clinical validation showed that the AI model had a sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 100.0%,98.5%,87.4%,100.0%and 98.7%for facial anatomy recognition,and the results were highly consistent with the classification of fetal ultrasound experts(k=0.925,P<0.001).The recognition accuracy of the model for 3 types of standard planes reached 100%;and the average speed of dynamic video detection was 33.93 frames per second.Conclusion The FFUSP recognition model based on real-time object detection network exhibits excellent performance,and it can be applied to real-time ultrasound diagnosis,teaching and intelligent quality evaluation.

Objective:The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) .Methods:Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed.Results:①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34 + cells [7.62×10 6 (2.26×10 6-37.20×10 6) /kg vs 2.73×10 6 (0.53×10 6-9.85×10 6) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) ( P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34 + cells infused in the two groups was 4.62×10 6 (2.14×10 6-19.89×10 6) /kg versus 2.62×10 6 (1.12×10 6-5.31×10 6) /kg ( P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d ( P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d ( P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion:The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34 + cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Purpose To explore the application of contrast-enhanced ultrasound in evaluating the local muscle microcirculation before and after acupuncture at Zusanli point in normal people.Materials and Methods A total of 72 healthy volunteers who visited the Department of Ultrasound,the Second Affiliated Hospital of Fujian Medical University from September 2018 to May 2020 were prospectively collected,all subjects performed ultrasound contrast before acupuncture,acupuncture with strongest deqi,and two hours after acupuncture to observe the blood flow perfusion of the microvessels in the tibialis anterior muscle.The pre-selected areas of interest the small arteries,muscle tissues and venules in the middle were analyzed to obtain the time-intensity curve and contrast transit time(CTTs)perfusion parameters.Needle sensation was evaluated using objective scoring criteria for acupuncture combined with moxibustion recipients.Gastrin,plasma gastrin,cholecystokinin,and secretin were measured in all subjects before acupuncture,when acupuncture had the strongest deqi,and two hours after acupuncture.Results ①CTTs of arterial-muscle,muscle-venous and arterial-venous of the tibialis anterior muscle at acupuncture with strongest deqi were significantly shorter than those at before acupuncture and two hours after acupuncture(all P<0.001),and there was no significant difference in CTTs before and after acupuncture and moxibustion(P>0.05);②when acupuncture deqi was strongest,serum gastrin,plasma prokinetics,cholecystokinin,and secretin were significantly increased compared with those before acupuncture and two hours after acupuncture,with statistically significant difference(all P<0.001),while there was no significant difference in these parameters between before acupuncture and two hours after acupuncture(P>0.05);③when acupuncture had the strongest deqi,there were positive correlations between gastrin,plasma prokinetic hormone,cholecystokinin,and secretin values and CTTs of arterial-muscle,muscle-venous,and arterial-venous(r=0.360-0.702,P<0.001).Conclusion Acupuncture of the Zusanli,when it gains the strongest deqi,can cause changes in the microcirculation around the skeletal muscle,leading to a significant shortening of CTTs,and also promotes the secretory function of the gastrointestinal tract.

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 investigate the clinical effect of microdissected peroneal artery perforator flap in repair of soft tissue defect of dorsal side of the fingers.Methods:From August 2015 to July 2020, 19 patients with soft tissue defects on dorsal fingers were treated with microdissected peroneal artery perforator flap. The area of wound defect was 3.8 cm×1.5 cm-5.8 cm×3.0 cm, with exposure of phalanges and tendons. The size of flaps was 4.0 cm×1.8 cm-6.0 cm×3.3 cm. According to the size of soft tissue defects on the dorsal side of the fingers, the flaps were designed with the perforating branch of peroneal artery in the centre. The length and width of a flap were 0.2-0.3 cm bigger and wider than the area of defect. The perforator vessels with a length of 2.0-3.0 cm were arvested in the superficial layer of deep fascia. Most of the adipose tissues of the flap were removed under microscope, and the small arteries between adipose tissues were protected. The flaps were used to cover the defects of fingers. The perforator artery of the flap was anastomosed with the proper palmar digital artery of the recipient site, the accompanying vein of the perforator artery was anastomosed with the dorsal digital vein of the recipient site, and the cutaneous nerve in the flap was anastomosed with the dorsal digital nerve. The donor sites were directly pulled together and sutured intermittently. Outpatient and WeChat follow-up were conducted after operation, including wound healing, flap survival, flap sensation, donor site recovery, and flexion and extension functions of the fingers. Functional recovery was evaluated according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Results:All wounds healed in Ⅰ stage, and all 19 flaps survived. The follow-up ranged from 9 to 25 months, with an average of 11.5 months. The appearance of the flaps was satisfactory and the texture was good. Sensation recoveried to S 4 in 4 paitients, S 3 in 9 patients and S 2 in 6 patients, and with only a linear scar was left in the donor sites. The hand function recovery was evaluated according to the Trial Criteria of Upper Limb Function Evaluation of the Hand Surgery Society of the Chinese Medical Association, with 18 cases were excellent and 1 was good. Conclusion:The microdissected peroneal artery perforator flap is an ideal surgical method to repair the soft tissue defect of dorsal side of the fingers, which has good shape and simple operation, avoids the secondary thinning and plastic surgery and offers good therapeutic effects.

Objective:To explore the clinical characteristics and predictors of severe acute pancreatitis complicated with acute respiratory distress syndrome (SAP-ARDS).Methods:Clinical data of consecutive 313 SAP patients hospitalized from January 2000 to January 2020 in Peking Union Medical College Hospital, were retrospectively analyzed, including 258 cases with ARDS (ARDS group) and 55 cases without ARDS (non-ARDS group). According to the severity of ARDS, ARDS group were further divided into mild ARDS group (165 cases) and moderate to severe ARDS group (93 cases). Clinical symptoms, laboratory examination and imaging results, ICU admission time and clinical outcome, as well as the local and systemic complications, acute physiology and chronic health evaluation (APACHEⅡ) within 24 h after admission, bedside index for severity in acute pancreatitis (BISAP), CT severity index (CTSI), sequential organ failure assessment (SOFA) and quick sequenctial organ failure assessment(qSOFA) score were recorded. Univariate and multivariate logistic regression were performed to analyze independent risk factors of SAP complicated with moderate to severe ARDS. Receiver operating characteristics curves (ROC) was drawn to calculate area under the ROC curve (area under curve, AUC) and evaluate the performance of WBC and hsCRP in predicting SAP complicated with moderate to severe ARDS, and assess the performance of APACHEⅡ, BISAP, CTSI, SOFA and qSOFA scores in predicting SAP-ARDS endotracheal intubation.Results:The ICU length of stay and mortality rate of SAP-ARDS patients were significantly higher than those without ARDS [(8.3±11.6 day vs 5.7±7.7 day, 12.4% vs 3.6%, all P value <0.05)]. Univariate analysis showed that elevated WBC ( OR 4.52, 95% CI 1.64-12.4) and hsCRP ( OR 3.69, 95% CI 1.29-10.48) on admission were independent risk factors for moderate to severe ARDS with SAP. The AUC of WBC and hsCRP for predicting SAP with moderate to severe ARDS at admission were 0.651(95% CI 0.532-0.770) and 0.615 (95% CI 0.500-0.730), respectively. The predicted cut-off values (Cut-off values) were 17.5×10 9/L and 159 mg/L, respectively, and the sensitivity was 53.1% and 78.1%, the specificity was 78.1% and 48.4% respectively. The area under the ROC curve for APACHEⅡ, BISAP, CTSI, SOFA, and qSOFA score 24 h after admission in the early prediction of endotracheal intubation were 0.739 (95% CI 0.626-0.840), 0.705 (95% CI 0.602-0.809), 0.753 (95% CI 0.650-0.849 ), 0.737 (95% CI 0.615-0.836) and 0.663 (95% CI 0.570-0.794), and the optimum Cut-off values were 14 points, 3 points, 5 points, 7 points, 2 points, and the sensitivity and specificity for these predictors were 58.8% and 81.4%, 79.4% and 60.0%, 73.5% and 67.1%, 38.2% and 98.6%, 45.5% and 83.3%, respectively. Conclusions::Elevated blood WBC and hsCRP on admission were independent risk factors for moderate to severe ARDS in SAP. APACHEⅡ≥14, BISAP≥3, CTSI≥5, SOFA≥7, or qSOFA≥2 within the 24 h admission indictaed that the risk of SAP patients to receive endotracheal intubation was high.

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.