ObjectiveTo investigate the safety and feasibility of intra-biliary drainage tube placement after laparoscopic common bile duct exploration in elderly patients with choledocholithiasis， and to provide more options for surgical procedures in the clinical management of elderly patients with choledocholithiasis. MethodsA retrospective analysis was performed for the clinical data of 52 elderly patients with choledocholithiasis who were admitted to Department of Hepatobiliary Surgery， Affiliated Dalian Friendship Hospital of Dalian Medical University， from November 2021 to October 2024. According to the biliary drainage method after surgery， the patients were divided into internal drainage group with 24 patients and T-tube drainage group with 28 patients， and there were 19 patients in each group after propensity score matching. The two groups were compared in terms of perioperative parameters and postoperative complications. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the T-tube drainage group， the internal drainage group had a significantly shorter length of postoperative hospital stay and a significantly lower volume of postoperative bile loss （Z=-2.845 and -5.633， both P<0.05）， while there were no significant differences between the two groups in time of operation， intraoperative blood loss， and drainage tube indwelling time （all P>0.05）. There were no significant differences between the two groups in postoperative bile leak， stone recurrence， biliary stricture， and drainage tube-related complications， and the internal drainage group had a significantly lower total complication rate than the T-tube drainage group ［1 （5.3%） vs 7 （36.8%）， P<0.05］. ConclusionFor elderly patients with choledocholithiasis， intra-biliary drainage tube placement after laparoscopic common bile duct exploration can shorten the length of postoperative hospital stay， reduce bile loss， and lower the incidence rate of postoperative complications， thereby helping to accelerate postoperative recovery.

Laparoscopic common bile duct exploration(LCBDE), as a safe and feasible surgical procedure for the treatment of choledocholithiasis, has been widely applied in clinical practice.However, due to the generally declined organ function, comorbidities, and polypharmacy associated with elderly patients, there is currently no unified consensus on the application of LCBDE in elderly patients with choledocholithiasis.This review aims to summarize the current status of LCBDE for the treatment of choledocholithiasis in the elderly patients, in order to provide reference for clinicians to select appropriate treatment strategies.

Laparoscopic common bile duct exploration(LCBDE), as a safe and feasible surgical procedure for the treatment of choledocholithiasis, has been widely applied in clinical practice.However, due to the generally declined organ function, comorbidities, and polypharmacy associated with elderly patients, there is currently no unified consensus on the application of LCBDE in elderly patients with choledocholithiasis.This review aims to summarize the current status of LCBDE for the treatment of choledocholithiasis in the elderly patients, in order to provide reference for clinicians to select appropriate treatment strategies.

OBJECTIVE To establish a method for the determination of polymyxin B concentration in plasma and apply it to clinical practice. METHODS After precipitated with 5% trichloroacetic acid solution， using polymyxin E2 as internal standard， the concentrations of polymyxin B1 and B2 in plasma sample were determined by UPLC-MS/MS. The determination was performed on BEH C18 chromatographic column with water （0.1% formic acid）-acetonitrile （0.1% formic acid） as mobile phase （gradient elution） at the flow rate of 0.5 mL/min. The sample size was 10 µL. The detection was accomplished with electrospray ionization operated in positive ion scanning by multi-reaction monitoring mode. The ion pairs for quantitative analysis were m/z 603.2→101.2 （polymyxin B1）， m/z 595.7→101.1 （polymyxin B2） and m/z 578.5→101.1 （internal standard）. The plasma concentration of polymyxin B in 79 critically ill patients was measured by the above method， the occurrence of acute renal injury （AKI） was recorded and the relationship of polymyxin B concentration in plasma with AKI was analyzed. RESULTS The linear ranges of polymyxin B1 and polymyxin B2 were 200-20 000， 50-5 000 ng/mL （r＞0.995）， and the lower limits of quantification were 200 and 50 ng/mL， respectively. RSDs of intra‐day and inter‐day precision tests were not higher than 12.06%， the average extraction recovery was 103.04%-117.44%， and RSDs of matrix effect test and stability test were all not higher than 7.42%. Steady state trough and peak plasma concentration were （2.54±2.52） and （8.17±5.20） mg/L for 79 clinical patients using polymyxin B. Eighteen patients out of 27 included patients developed AKI， with an incidence of 66.67%. The peak concentration of polymyxin B of patients without AKI was significantly lower than that of patients with AKI （P＜0.05）， but there was no significant difference in the trough concentration between two groups （P＞0.05）. CONCLUSIONS The established UPLC-MS/MS has the advantages of simple operation and high sensitivity， and can be used to monitor the plasma concentration of polymyxin B in patients. The occurrence of AKI is correlated with the peak concentration of polymyxin B.

OBJECTIVE To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic. METHODS The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （c0） and plasma concentration of voriconazole-N-oxide concentration （cN） were determined， and voriconazole-to-voriconazole N-oxide concentration ratio （c0/cN） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for c0 and c0/cN of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for c0 and c0/cN of voriconazole. RESULTS The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly Aspergillus， Candida and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with c0 of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole c0. The levels of CRP， TBIL and DBIL were positively correlated with c0/cN， while albumin levels were negatively correlated with c0/cN. Multiple linear regression analysis showed that the independent influencing factors of voriconazole c0 included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole c0/cN were the levels of CRP and DBIL and age. CONCLUSIONS The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole c0； the levels of CRP and DBIL and age are independent influencing factors of voriconazole c0/cN. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.

Objective:To study the environmental characteristics of launch section during the space medical rescue mission of Shenzhou-13 spacecraft, evaluate the influence of special environment on peripheral veins, and investigate the coping strategies.Methods:Combined with the practice of launch section during space medical rescue mission of Shenzhou-13 spacecraft, the main factors of aerospace special environment, cold and faint light, were selected and the related literature was reviewed to explore the feasibility, advantages and disadvantages of peripheral venipuncture, central venous catheter and bone marrow puncture. The experience of the space medical rescue mission was summarized and the coping strategies were provided for follow-up task training.Results:The environmental characteristics of launch section during the space medical rescue mission of Shenzhou-13 spacecraft included cold, faint light, sand-wind and complex terrain. The vascular filling, vascular elasticity and visibility of peripheral vein decreased in different degrees under special environmental, the vascular visibility was most affected. The literature analysis showed that bone marrow puncture was a suitable method to establish infusion access in cold and faint light environment.Conclusions:The special environment of space launch mission has greater impact on peripheral veins. In order to assurance the successful implementation of manned space project, the training of basic operational skills should be consolidated, the training of ability in special environment should be enhanced and the advanced clinical auxiliary equipment should be equipped in follow-up space medical mission training.

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

Objective: To investigate the feasibility and accuracy using digital surgical guide to position the jaws in bimaxillary orthognathic surgery. Methods: 16 patients with dento-maxillofacial deformity were included from January to December 2018 in Nanjing Stomatological Hospital. There were 10 males and 6 females, all of which were skeletal Ⅲ deformity. The mean age was 21.3 years old (16 to 28 years). They were divided into digital guide (group A) and traditional model surgery (group B) according to the treatment sequence. All patients underwent both Lefort Ⅰ osteotomy and bilateral ascending sagittal split. Virtual surgery was performed and digital three-dimensional surgical template was printed before surgery in group A. During the operation, digital surgical templates were used to position maxilla and mandible. The accuracy was evaluated by generating color distribution map of deviation grade, which was imaging fusion of virtual surgical jaw position and actual surgical jaw position to measure the deviation distance of each marker point one week after surgery. The deviations between the preoperative design and the actual operation were compared with the t-test respectively in group A and group B, and the independent sample t test was chosen to compared the accuracy of reduction between the two groups in sagittal, horizontal, and vertical directions. Results: All 16 patients had primary healing. The maximum deviation of the patients in group A was at U6. The deviation direction was vertical, and the deviation distance was (1.67±0.32) mm. In group A, the deviation distances of all marker points in the sagittal, horizontal and vertical directions were (0.55±0.26) mm (t=2.985, P=0.205), (0.62±0.20) mm (t=2.672, P=0.193) and (1.07±0.62) mm (t=5.122, P=0.823), respectively. The result in group B was (0.63±0.28) mm(t=3.397, P=0.307), (0.71±0.42) mm (t=4.438, P=0.541) and (1.82±0.36) mm (t=1.115, P=0.021) in these directions. There was no significant difference between two groups in the sagittal (t=4.704, P=0.763) and lateral (t=4.008, P=0.615) directions, and the difference in the vertical (t=1.432, P=0.037) direction was statistically significant. Conclusions The digital guides were feasible to position jaws accurately in orthognathic surgery.

Objective: To describe the influence of post-operative anatomical structure changes on nasal airflow characteristics by 3D reconstruction and numerical simulation in real cases after nasalisation with Draf Ⅲ so as to explore the correlation between the changes of anatomical structure and subjective symptoms as well as airflow characteristics. Methods: Ten patients underwent nasalization with Draf Ⅲ in Department of Rhinology in Beijing Tongren Hospital from 2006 to 2018 were selected retrospectively. Postoperative follow-up of all patients was more than 1 year. All patients had no abnormalities in their paranasal sinus CT scans and Lund-Kennedy scores were 0 except scar. VAS scores including nasal obstruction, stimulation in frontal sinus, and headache were collected at the same period. The control model was a normal person. Numerical simulation was used for calculating airflow characteristics in deep inspiratory period of both models. Independent sample Mann-Whitney U test and Spearman correlation test were used by software SPSS 22.0. Results: The airflow pressure in frontal sinus ostium was (7.21±1.39)×10⁴ Pa (Mean±SD), which was lower than that in normal subjects (8.99×10⁴ Pa) under deep inspiratory simulation. But, the velocities in frontal sinus ostium and frontal sinus were (40.10±2.46) m/s and (28.19±1.73) m/s respectively, which were higher than those in normal one (2.70 m/s, 0.73 m/s). The airflow patterns of the two models were basically similar. There was no significant difference in the opening size and volume of frontal sinus between different groups after grouped by three symptoms respectively. No correlation could be found between the opening size and volume of the frontal sinus with the appearance and severity of three subjective symptoms. Conclusions The airflow pattern and distribution after nasalisation with Draf Ⅲ are like those of normal person. There is no correlation between the changes of anatomy in frontal recess and frontal sinus and nasal airflow characteristics as well as subjective symptoms.

Objective:Immunoregulation study of umbilical mesenchymal stem cell (UCMSCs) on allogeneic umbilical cord blood(UCB) CD4+T lymphocytes,which proliferation,apoptosis and the differentiation to CD4+CD25+ regulatory T cell (Treg) in vitro. Methods:Establishing on direct contact or transwell co-culture system,adopt in different proportion of UCMCs with phytohaemag-glutinin (PHA)-activated UCB CD4+T lymphocytes were co-cultured. The proliferation of lymphocyte,percent of CD4+CD25+/CD4+and Foxp3 expression, regulatory T cell marker gene were measured. Apoptosis of CD4+T lymphocytes were observed in the direct contact or transwell coculture system of UCMSCs with desamethason( DXM)-stimulated UCB CD4+T lymphocytes. Results: The UCB CD4+T lymphocytes cocultured with UCMSCs with PHA-activating for 3 days,compared with the UCMSCs free control group,the amount of cells was reduced noticeably(P<0. 05) and the percent of CD4+CD25+in CD4+T lymphocytes and Foxp3 expression significantly in-creased(P<0. 01) in a dose dependent way(P<0. 05). The UCB CD4+T lymphocytes cocultured with UCMSCs with DXM-inducing for 7 days,the apoptosis rate was significantly lower than that of the control group without UCMSCs (P<0. 01). These effects were partially attenuated in transwell coculture but could not be eliminated. Conclusion: UCMSCs are negative effect on UCB CD4+T lymphocytes-mediated immunity effects,and mainly manifested in the regulation on cell proliferate ability and differentiation rather than promoting apoptosis.