ObjectiveTo investigate value of minimally invasive surgical approach in patients with hypertensive intracerebral hemorrhage in primary hospital.MethodsAccording to the operation procedure,93 cases with basal ganglia hemorrhage were divided into three groups:1.minimally invasive surgery group A (n =37 ),2.ventricular puncture and drainage,lumbar cistern drainage group B(n=10),3.usual operation group C( n =46).Estimated operation effect with computed tomography in 24 hours after operation.Case fatality rate and complication incidence were analyzed after three months of operation according to the Glasgow Outcome Scale (GOS).ResultsMinimally invasive surgery group A had the highest hematoma clearance rate (82.7 ± 8.1 ) ％,group B (78.6±6.5 ％ ),group C (50 ±10％ ).The incidence rate of rebleeding was 8.1％ in group A( n =3 ),10％ in group B ( n =1 ),34.8％ in group C (n =16).The grade Ⅳ of the GOS and the grade Ⅲ of the GOS was respectively 93.8％ and 6.5％,case fatality rate was zero.Conclusion The minimally invasive surgical operation not only lead to less tissue damage and decrease rebleeding,but also improve neurological functional recovery.

This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours (AUC(0-24 h)). Limited sampling strategy (LSS) models was developed and validated by mutiple regression model within 4 or fewer amlodipine concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual predict check were used as criterion. The results of Jackknife validation showed that fifteen (9.4%) of the 160 LSS based on regression analysis were not within an APE of 15% by using one concentration-time point. 156 (97.5%), 159 (99.4%) and 160 (100%) of the 160 LSS model were capable of predicting within an APE 15% by using 2, 3, 4 points, separately. Limited sampling strategies have been developed and validated for estimating AUC(0-24 h) of amlodipine. The present study indicated that the implemention of both 5 mg and 10 mg dosage could enable accurate predictions of AUC(0-24 h) by the same LSS model. This study shows that 12, 4, 24, 2 h after administration are key sampling time points. The combination of (12, 4), (12, 4, 24) or (12, 4, 24, 2 h) might be chosen as sampling hours for predicting AUC(0-24 h) in practical application according to requirement.

BACKGROUND: Previous studies have confirmed that in the animal models of articular cartilage defects and osteoarthritis, the chondrocytes can overexpress the matrix metal oproteinases. Various abnormal stimuli are likely to break the balance between matrix metal oproteinase and tissue inhibitor of metal oproteinase, thus leading to degeneration of extracel ular matrix of articular cartilage, as wel as the decline and offset of cartilage chondrocytes. OBJECTIVE: To observe the effect of cyclic tensile strain on the expression of matrix metal oproteinases during the repairing process of rabbit articular cartilage defects. METHODS: The animal models of articular cartilage defects were established, and chondrocytes were separated for culture at 10 weeks after operation. The chondrocytes on the non-surgical side were considered as the normal group, and the chondrocytes on the surgical side were randomly divided into high cyclic tensile strain group, low cyclic tensile strains group and control group, and the load amplitude was sin10%. Then 0.1, 1.0 and 0 Hz cyclic tensile strains were loaded respectively. The expressions of matrix metal oproteinases 2, 3, 9 and 13 in each group were detected with reverse transcription-PCR at 24, 48 hours, 1, 2 and 4 weeks after loading cyclic tensile strain. RESULTS AND CONCLUSION: There were significant differences in the expressions of matrix metal oproteinases 2, 3, 9 and 13 at 24 hours after loading cyclic tensile strain between the normal group and the control group (P < 0.05); and there were significant differences in the expressions between the high cyclic tensile strain group and the low cyclic tensile strain group at 1, 2 and 4 weeks after loading cyclic tensile strain (P < 0.05).At the same time, the expressions of matrix metal oproteinases 2, 3, 9 and 13 in the low cyclic tensile strain group were continued to decline, and there were significant differences in the expressions after loading cyclic tensile strain for 24 hours and 4 weeks (P < 0.05). The results indicate that mechanical load can affect the expression of matrix metal oproteinases in the healing process of rabbit articular cartilage defects. In the cel ular and molecular level, the incidence and development of pathological articular cartilage defect and stress should affect each other.

Objective:To explore CT and MRI features of the endolymphatic sac tumor (ELST).Methods:The CT and MRI morphology confirmed by surgical pathology for 19 patients with ELST were retrospectively analyzed from June 2011 to May 2019 in Eye & ENT Hospital of Fudan University. The features of CT and MRI included location, size, adjacent structures invasion, CT values, bone destruction, features of T 1WI and T 2WI, enhancement distribution characteristics, dynamic enhancement curve morphology, DWI signal characteristics. The ADC values of the lesions and ipsilateral medial pterygoid muscles were compared using a paired t test. Results:Nineteen ELST patients (one with bilateral diseases) were included. Totally 20 ears (right 9 and left 11) of 13 females and 6 males were studied. The masses with slightly high-density and obscure boundary were located around the vestibular aqueduct at the posterior edge of the petrosal bone. Bone destruction involved mastoid process of the middle ear (16 ears), jugular foramen (11 ears), semicircular canal (10 ears), facial nerve canal (7 ears) and internal auditory canal (9 ears). A large amount of residual bone could be found in the interior of nineteen masses. The CT value was (78.6±21.9) HU. The lesion showed central iso-intensity and peripheral hyperintensity on T 1WI and T 2WI in 16 ears, while no obvious hyperintensity on T 1WI in the other 4 ears. The hyperintensity on T 1WI was around the margin of the lesion in 10 ears, situated at lateral side in 5 ears and all over the lesion in 1 ear. Flow voids signals could be seen in 9 ears as well. Liquid-liquid plane was seen on T 2WI in 2 ears. The solid mass portion which showed iso-intensity on both T 1WI and T 2WI presented marked enhancement on contrast-enhanced T 1WI, while other part of the mass no enhancement. DWI of 14 ears illustrates no evidence of restricted diffusion, and the ADC value [(1.25±0.08)×10 -3 mm 2/s] was slightly higher than that of the medial pterygoid muscles ( t=4.437, P=0.001). The style of time-signal intensity curves of the dynamic contrast-enhanced MRI was rapidly ascending followed by descending curves in 2 ears. Conclusion:Imaging findings of ELST have some characteristics, including located around the vestibular aqueduct at the posterior edge of the petrosal bone, bone destruction, peripheral hyperintensity on T 1WI and no restricted diffusion, which is helpful for its diagnosis.

Objective To investigate the value of GPS score and CEA in predicting the prognosis of pa-tients with colorectal cancer undergoing laparoscopic surgery. Methods 120 patients diagnosed as colorectal can-cer in our hospital were involved and their baseline information include Height,weight,history,complication, course of disease,tumor size,pathological type,tumor location,TNM stage,vascular tumor thrombus and lymph node metastasis were recorded. Then,all of the patients were followed-up 18 months and patients with favorable prognosis were defined as the favorable group while patients with unfavorable prognosis were defined as the unfavor-able group. Cox′s proportional hazard regression model analysis was applied to evaluate the influencing degree of those factors on the prognosis of the subjects. The factors in predicting prognosis were calculated by ROC curves. Results The poor prognosis rate of patients with colorectal cancer after operation treatments was 37.84%. Cox′s proportional hazard regression model analysis showed that CEA(P = 0.035),GPS score(P = 0.023)have influenc-es on the prognosis. Conclusion GPS scores and CEA may assess the prognosis of patients with colorectal cancer undergoing laparoscopic surgery,which is expected to be used as an indicator of predicting the prognosis of pa-tients with colorectal cancer undergoing laparoscopic surgery.

Objective:To evaluate the clinical application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali in the treatment of intra-articular calcaneal fractures.Methods:From January 2016 to January 2019, 68 patients were treated at Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for intra-articular calcaneal fractures of Sanders types Ⅱ-Ⅳ. According to different designs of screw placement into the sustentaculum tali, they were assigned into a control group (38 cases and 42 feet) and an observation group (30 cases and 33 feet). There were 24 males and 14 females with an age of 39.3 years±8.8 years in the control group. There were 17 males and 13 females with an age of 42.0 years ± 7.6 years in the observation group. The control group was given a routine placement design based on the X-ray and MSCT scanning images of the injured feet. In the observation group, a Mimics model was first constructed using the X-ray and MSCT scanning images of the normal or less injured feet for further virtual screw placement into the sustentaculum tali on a 3D printed model. The disparity was investigated between the parameters designed and the actual values in both groups. The 2 groups were compared in terms of average placements, screw distribution, placement accuracy, placement time and Maryland scores of foot function one year after operation.Results:There were no significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The design parameters and actual values in the control group were respectively as follows: 17.7°±3.2° versus 15.1°±5.9° in upward oblique angle, 20.3°±2.1° versus 16.2°±6.8° in backward oblique angle, and 47.9 mm ± 3.8 mm versus 45.4 mm ± 4.2 mm in length of screw path, showing significant differences ( P< 0.05). The design parameters and actual values in the observation group were as follows: 16.5°±3.5° versus 17.1°±3.9° in upward oblique angle, 20.9°±4.3° and 19.6°±3.8° in backward oblique angle, and 48.1 mm ± 3.1 mm versus 47.3 mm ± 3.8 mm in length of screw path, showing insignificant differences ( P>0.05). The average screw placements into the sustenta culum tali in the observation group (1.6±0.5) were significantly more than those in the control group (1.2±0.4). Compared with the control group, the observation group had a higher rate of placement of 2 screws[60.6 % (20/23) versus 16.7% (7/42)], higher accuracy of placement [94.3% (50/53) versus 77.6% (38/49)], less placement time for each screw (9.6 mm±3.9 min versus 13.2 mm±4.7 mm), less placement time for each foot (15.6 mm±4.8 min versus 20.5 mm±3.8 mm), and higher Maryland scores at one year after operation (94.2±6.5 versus 89.7±6.9). All the above comparisons were statistically significant ( P<0.05). Conclusions:Application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali can improve the outcomes of intra-articular calcaneal fractures, because it increases the number of screws placed, enhances quality of screw placement, shortens operation time, and thus facilitates functional recovery of the injured foot.

Objective:To explore the safety and clinical value of ultrasound-guided percutaneous core needle biopsy in the diagnosis of cardiac intermural tumors and pericardial tumors.Methods:Seven patients who underwent ultrasound-guided percutaneous cardiac tumors needle biopsy in Fujian Provincial Hospital from January 2012 to December 2019 were selected for this study. The locations and sizes of the lesions were recorded preoperatively by echocardiography and the operation time was recorded by conventional ultrasonography. The postoperative complications was followed up, and the satisfaction of pathological materials was used as the evaluation standard to comprehensively analyze the safety and clinical application value of ultrasound-guided percutaneous biopsy in the diagnosis of cardiac tumors.Results:Ultrasound-guided percutaneous biopsy was performed successfully in all the 7 cases, 3 of them were intermural tumors and 4 of them were pericardial tumors. Except for 2 patients with diffuse pericardial space, the maximum diameter of the remaining 5 patients was (58.6±23.5)mm. Six cases were punctured from the apex of the heart, and 1 case from the left parasternal through third intercostal space toward the bottom of the heart as the needle pathway. The satisfaction of pathological material was 100%, and the time of procedure was (15.1±3.3)min. There were no postoperative complications such as bleeding, infection or arrhythmia.Conclusions:Ultrasound-guided percutaneous transthoracic needle biopsy is safe and feasible, which provides a simple and easy method for the biopsy of cardiac intramural tumors and pericardial tumors.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.
Female ; Humans ; Proto-Oncogene Proteins c-akt ; Phosphatidylinositol 3-Kinases ; Endometrial Neoplasms ; Estrogens ; Breast Neoplasms ; DNA Helicases

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.