Objective:To prepare the cyclosporin A(CsA) polylactic acid microspheres using solvent evaporation method from an oil-in-water system.Methods:Orthogonal experiment was used to optimize the method of CsA polylactic acid microspheres preparation.The microspheres were characterized for drug loading and entrapment efficiency by high-performance liquid chromatography(HPLC),average size by particle size analyser and surface morphology by scanning electron microscopy(SEM).In vitro the release kinetics were studied using a modified dialysis method.Results:SEM studies showed discrete and spherical particles with smooth surfaces.The average particle size was 18.234 ?m,with more than 80% of the microspheres falling in the range of 9.525-32.400 ?m.The drug loadings ranging was(34.51?0.63)% with a high encapsulation efficiency(86.12?0.77)% determined by HPLC.In vitro release study revealed a profile of sustained release of CsA from CsA-PLA-MS.The accumulated release percentage of CsA microspheres were 40.8% in 30 d.CsA release profiles show CsA release could be divided by two different phases,fast release within the first few days and the subsequent sustained release.Conclusion:CsA polylactic acid microspheres have been successfully prepared and sustained release of CsA from microspheres have been achieved.

Objective To provide accurate bone tunnel positioning reference for clinical individual anterior cruciate ligament (ACL) reconstruction by three-dimensional (3D) reconstruction of femoral and tibial original footprint of ACL.Methods Forty volunteers were selected for this study,including 20 males and 20 females,and aged 18 to 35 years old.3D CT scanning images of knee data were obtained.3D bone models of knee and footprint of ACL were reconstructed.On the 3D reconstruction models,the shape and position of original footprint of ACL were displayed.Statistical significance was compared for their difference.Results Femoral original footprint of ACL,long axis of footprint,distances to the distal margin of the articular cartilage (DDCM),distances to the posterior margin of the articular cartilage (DPCM),double bundle center distance,and tibial original footprint short axis of ACL were significantly different between genders (P ＜ 0.05).However,no significant difference was found between genders for tibial original footprint long axis of ACL (P ＞ 0.05).Conclusions The insertion mark shape and nature position of footprint of ACL could be observed by 3D reconstruction using CT scan images.

OBJECTIVETo verify the existence and significance of calcium/calmodulin dependent serine protein kinase/inhibitors of differentiation 1 (CASK/Id1) pathway in fibroblasts of human keloid.

METHODSImmunofluorescence laser was used to confirm CASK and Id1 protein expression and localization in fibroblasts of the keloid and normal skin. RT-PCR and Western-blot were adopted to analysis the CASK and Id1 expression and differences between keloid and normal skin fibroblasts. The natural combination of CASK and Id1 protein of keloid fibroblasts was tested by immunoprecipitation.

RESULTSCASK and Id1 protein expression were both found in fibroblast cells of keloid and normal skin under normal circumstances. Most of CASK and Id1 were distributed in the cytoplasm and nucleus of fibroblasts. The results of RT-PCR showed that the expression of CASK mRNA in the keloid group was 0.658 +/- 0.024, which was lower than that in the normal control group (1.076 +/- 0.008, t = 11.159, P < 0.05). The expression of Id1 mRNA was 0.497 +/- 0.014, which was higher than that in the normal control group (0.307 +/- 0.017, t = 15.148, P < 0.05). The results of Western-blot showed that the expression level for CASK protein in the keloid group was 0.057 +/- 0.006, which was lower than that in the normal control group (0.168 +/- 0.012, t = 13.524, P < 0.05); the expression of Id1 protein was 0.812 +/- 0.035, which was higher than that in the normal control group (0.368 +/- 0.031, t = 16.356, P < 0.05). The results of immunoprecipitation showed that Id1 could be detected in the CASK precipitate, while CASK also could be detected in the Id1 precipitate. There was a natural binding of CASK and Id1 in keloid fibroblasts.

CONCLUSIONCASK/Id1 signal pathway may be existed and involved in the proliferation of keloid fibroblasts, which is related with the occurrence of keloid.

Cell Proliferation ; genetics ; Cyclin-Dependent Kinase Inhibitor Proteins ; genetics ; metabolism ; Fibroblasts ; metabolism ; Humans ; Inhibitor of Differentiation Protein 1 ; genetics ; metabolism ; Keloid ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Signal Transduction

Approach-avoidance conflict(AAC)refers to the internal conflict that individuals experi-ence when faced with conflicting approach or avoidance thoughts.It reveals some characteristics of mental disorders,such as anxiety,depression,and addiction represented by excessive tendencies of approach or avoidance.The function of the cortico-limbic-striatal system influences behavioral choices at the neural level during the onset of AAC,and the development of related behavioral paradigms that can better represent AAC behaviors is critical to evaluating the efficacy of drugs and guiding the development of new drugs.This paper summarizes the neural mechanisms,behavioral paradigms,and applications in behavioral pharmacology related to AAC behaviors from the perspective of psychopharmacology with a view to providing new perspectives and methods for the diagnosis and treatment of related neuro-psychiatric disorders.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Objective To evaluate the therapeutic efficacy and safety of HIFU ablation for uterine fibroids in patients with abdominal surgical scars in acoustic pathway causing acoustic attenuation width ＜10 mm.Methods Totally 861 patients with uterine fibroids were referred for HIFU treatment and underwent contrast-enhanced MR scans before and after HIFU ablation.Among all patients,202 had abdominal surgical scars causing width ＜10 mm acoustic attenuation (abdominal scars group) and 659 had no abdominal surgical scars (without abdominal scars group).The outcomes,intra-operative adverse reactions and post-operative complications between the two groups were compared.Results HIFU ablation was successfully performed in all patients.The volume ablation rate was (80.31 ± 18.16)％ in abdominal scars group and (79.60±17.57)％ in without abdominal scars group (P＝0.620).The rate of ‘hot'skin sensation during HIFU procedure in abdominal scars group (52.97％ [107/202]) was higher than that in without abdominal scars group (41.58％ [274/ 659];P＝0.004).Anterior abdominal wall edema was found in 40 cases (40/202,19.80％) in abdominal scars group and 98 cases (98/659,14.87％) in without abdominal scars group on post-operation MRI (P＝ 0.095).Conclusion Prior abdominal surgical scars in acoustic pathway causing width ＜10 mm acoustic attenuation has not significantly influence on the efficacy and safety of HIFU treatment for uterine fibroid.

Minute pulmonary meningothelial-like nodules (MPMNs) are benign small lesions in the lungs, with similar pathological characteristics to the meningeal epithelium. MPMNs have similar imaging manifestations to malignant tumors, which can lead to misdiagnosis in clinical practice. There is no consensus on the pathogenesis of MPMNs, with some suggest that MPMNs derive from reactive proliferation, while others suggest that MPMNs share a common origin and molecular mechanism with meningiomas in the central nervous system. Understanding the characteristics of MPMNs and studying their pathogenesis will help improve the understanding and diagnosis of MPMNs. In this article, we reviewed the clinical, pathological, imaging characteristics, differential diagnosis and pathogenesis of MPMNs. We also analyze the existing research advances regarding the pathogenesis and propose prospects for further research.
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