ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Objective:To explore the teaching effect of 3D simulated wound model combined with problem -based learning (PBL) teaching in the standardized residency training of plastic surgery department. Methods:Totally 90 residents trained in the plastic surgery department of Changhai Hospital of Naval Medical University from June 2016 to September 2019 as the research objects were divided into control group and experimental group in average. The control group received traditional teaching and the experimental group accepted the 3D simulated wound model combined with PBL teaching. Then the out -department examination results and questionnaires evaluation were compared between the two groups. SPSS 19.0 was used to conduct t test on the experimental data. Results:The theoretical and practical scores of residents in the experimental group [(49.23±7.25) points and (36.38±5.29)] points were significantly better than those in the control group [(44.43±5.57) points and (28.94±6.97)] points ( P<0.05). In the questionnaire, the scores of active learning initiative, practical operation ability and clinical strain capacity of residents in the experimental group were all higher than those in the control group ( P<0.05), and there was no statistically significant difference in teamwork ability between the two groups ( P>0.05). Conclusion:The 3D simulated wound model combined with PBL teaching can be used in the teaching of standardized residency training of plastic surgery. Compared with traditional teaching, this teaching method has significant advantages and is worthy of promotion.

Objective:To systematically summarize and assess risk prediction models for occurrence of cervical cancer and to provide evidence for selecting the most reliable model for practice, and guide cervical cancer screening.Methods:Two groups of keywords related to cervical cancer and risk prediction model were searched on Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library). Original articles that developed or validated risk prediction models and published before November 21, 2019, were selected. Information form was created based on the CHARMS checklist. The PROBAST was used to assess the risk of bias.Results:12 eligible articles were identified, describing 15 prediction models, of which five were established in China. The predicted outcomes included multiple stages from cervical precancerous lesions to cancer occurrence, i.e., abnormal Pap smear (1), occurrence or recurrence of CIN (9), and occurrence of cervical cancer (5), etc. The most frequently used predictors were HPV infection (12), age (7), smoking (5), and education (5). There were two models using machine learning to develop models. In terms of model performance, the discrimination ranged from 0.53 to 0.87, while only two models assessed the calibration correctly. Only two models were externally validated in Taiwan of China, using people in different periods. All of the models were at high risk of bias, especially in the analysis domain. The problems were concentrated in the improper handling of missing data (13), preliminary evaluation of model performance (13), improper use of internal validation (12), and insufficient sample size (11). In addition, the problems of inconsistency measurements of predictors and outcomes (8) and the flawed report of the use of blindness for outcome measures (8) were also severe. Compared with the other models, the Rothberg (2018) model had relatively high quality. Conclusions:There are a certain number of cervical cancer risk prediction models, but the quality is poor. It is urgent to improve the measurement of predictors and outcomes, the statistical analysis details such as handling missing data and evaluation of model performance and externally validate existing models to better guide screening.

Objective:To study whether curcumin inhibits the proliferation and promotes the apoptosis of nephroblastoma through activating the miR-192-5p/PI3K/Akt signaling pathway.Methods:CCK-8 assay was used to investigate the effects of curcumin on the proliferation of nephroblastoma SK-NEP-1 cells and the appropriate concentration. The apoptosis rate of SK-NEP-1 cells was detected by V-FITC/PI. Luciferase reporter assay was used to verify the binding activity between miR-192-5p and PI3K. RT-PCR was performed to detect the expression of miR-192-5p at mRNA level. Western blot was used to detect the expression of PI3K and Akt at protein level.Results:Curcumin could significantly inhibit the proliferation of SK-NEP-1 cells and induce cell apoptosis in a dose-dependent manner. RT-PCR results showed that curcumin could significantly increase the expression of miR-192-5p. In addition, miR-192-5p significantly inhibited cell proliferation, induced cell apoptosis, and enhanced the effects of curcumin on the proliferation and apoptosis of SK-NEP-1 cells. Luciferase reporter assay suggested that miR-192-5p could bind to PI3K. Western blot results showed that curcumin down-regulated the expression of PI3K and Akt at protein level by mediating the expression of miR-192-5p.Conclusions:Curcumin could inhibit the proliferation and induce the apoptosis of nephroblastoma cells through mediating the expression of miR-192-5p and further inhibiting the downstream PI3K/Akt signaling pathway.

Objective:To investigate the application and effect of frontal flap combined with tarsalconjunctiva flap in the repair of widely full-thickness defects of the lower eyelid.Methods:From January 2016 to March 2018, 9 patients with extensive full-thickness lower eyelid defect were admitted to the Plastic Surgery Department of Changhai Hospital Affiliated to the Naval Military Medical University. All the lengths of lower eyelid defects were greater than a half of the full length. Then we designed forehead flaps combined with tarsalconjunctival flaps to cover the wounds. The second stage operation was done after 4-6 weeks to cut the pedicle and dress the eyelid.Results:All the frontal flaps of 9 patients survived. One patient had lower eyelid retraction and the lid position returned to normal half a year later. One underwent thinning surgery because of lower eyelid flap hypertrophy and one were because of pedicle hypertrophy. The appearance and function of other patients were greatly improved after surgery, and they were satisfied with the operation effect. No repair operation was performed in the future.Conclusions:The frontal flap with good quality of blood supply has a high survival rate and can be used to repair the wide defect of the lower eyelid with tarsalconjunctival flaps.

Objective:To investigate the application and effect of frontal flap combined with tarsalconjunctiva flap in the repair of widely full-thickness defects of the lower eyelid.Methods:From January 2016 to March 2018, 9 patients with extensive full-thickness lower eyelid defect were admitted to the Plastic Surgery Department of Changhai Hospital Affiliated to the Naval Military Medical University. All the lengths of lower eyelid defects were greater than a half of the full length. Then we designed forehead flaps combined with tarsalconjunctival flaps to cover the wounds. The second stage operation was done after 4-6 weeks to cut the pedicle and dress the eyelid.Results:All the frontal flaps of 9 patients survived. One patient had lower eyelid retraction and the lid position returned to normal half a year later. One underwent thinning surgery because of lower eyelid flap hypertrophy and one were because of pedicle hypertrophy. The appearance and function of other patients were greatly improved after surgery, and they were satisfied with the operation effect. No repair operation was performed in the future.Conclusions:The frontal flap with good quality of blood supply has a high survival rate and can be used to repair the wide defect of the lower eyelid with tarsalconjunctival flaps.

Objective To explore the effect of first-line anti-tuberculosis treatment on vitamin D level in patients with pulmonary tuberculosis,and to master the changes of vitamin D level in the course of treatment,so as to provide a scientific basis for tuberculosis and nutrition health education in Shenzhen.Methods A total of 100 patients diagnosed as smear-positive pulmonary tuberculosis and receiving initial treatment in 2016 were enrolled and all the patients were treated with the standardized short-course chemotherapy regimens.The blood samples were extracted before treatment and at the ends of intensive and continuation phase.The 25-hydroxyvitamin D [25-(OH) D] concentrations were determined by chemiluminescence (CLIA) at each time point.The change of 25-(OH) D concentrations during anti-tuberculosis treatment was analyzed and the differences of vitamin D levels between different time points were identified.Results 79 (79.0％),94 (94.0％) and 96 (96.0％) patients were found vitamin D deficiency before treatment and at the end of the intensive and continuation phases respectively,which showed an upward trend (x2=15.543,P＜0.001) and the 25-(OH)D concentrations were (15.74±6.54) ng/ml,(12.56±5.15) ng/ml,(11.51±4.28) ng/ml,respectively.During the whole course of treatment,the 25-(OH) D concentration decreased by 26.9％ or (4.23 ± 6.75) ng/ml (t =6.257,P＜0.001),wherein it decreased (3.18 ± 5.24) ng/ml in intensive phase (t =6.069,P＜ 0.001) and (1.05±4.86) ng/ml in continuation phase (t =2.154,P =0.034).The former had a greater decreased value (t=2.836,P=0.006).There were 77 (77.0％) and 55 (55.0％) patients with 25-(OH)D concentration reduction in intensive and continuation phases respectively (x2 =9.680,P =0.003),of which 41 patients (41.0％) continued to decline.Conclusion Once anti-tuberculosis treatment is conducted,the vitamin D level will decrease rapidly in the intensive phase and continue decreasing throughout the course of treatment,which leads to a general lack of vitamin D in patients with primary pulmonary tuberculosis.First-line anti-tuberculosis drugs may be the main cause for vitamin D level reduction.Therefore,it is necessary for clinicians to strengthen vitamin D health education for each patient throughout the treatment period,especially for those at high risk of vitamin D deficiency who should be recommended adjuvant vitamin D supplementation therapy.

Objective: To investigate the lateral canthoplasty and canthopexy with bone drilling to correct lower eyelid malposition and its benefit. Methods: From January 2014 to January 2019, lateral canthopexy with bone drilling technique was used to repair 56 patients with lower eyelid malposition in Department of Plastic and Reconstructive Surgery of Changhai Hospital. Forty-four patients with lower eyelid ectopic had multiple previous surgeries, and 12 patients had congenital lower eyelid retraction. For patients without lower palpebral margin extension, lateral canthopexy with bone drilling technique was applied. For patients with lower palpebral margin extension, the lateral canthus angle was exposed to shorten the lower eyelid margin. For congenital lower eyelid retraction, the lateral canthus tendon was completely cut off, and then fixed with double armed sutures. Results: Operations were successfully performed on all 56 patients, and the patients were followed up for 1-38 months. Forty-nine patients achieved good eyelid shape and satisfied with the operative effects (87.5%). Malposition was ameliorated in 6 patients (10.7%). One remained uncorrected (1.8%). Conclusions Lateral canthopexy with bone drilling technique could obtain firm suspension force. For lower eyelid malposition, especially for patients with recurrent malposition or congenital lower eyelid retraction, satisfied function and appearance could be achieved.

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
China ; Humans ; Liver Transplantation

Objective: To determine the levels of vitamin D in patients with pulmonary tuberculosis in Shenzhen and identify the influencing factors of vitamin D levels and key groups of vitamin D deficiency, so as to provide a scientific basis for tuberculosis- and nutrition-related health education and promotion in Shenzhen. Methods: Patients with smear-positive pulmonary tuberculosis who were diagnosed in 2016 were selected as the research subjects. Their relevant information and blood samples were collected, and the sample pool was established according to the inclusion criteria. One hundred and twenty patients were selected based on simple random sampling, including 84 men (70.0%) and 36 women (30.0%). Blood 25-hydroxyvitamin D [25(OH)D] concentrations were measured using chemiluminescence technology. Vitamin D statuses in patients were statistically described, and vitamin D levels in patients with different characteristics were compared. Multivariate linear regression analysis was performed to identify important factors influencing vitamin D levels in patients. Results: Mean serum concentration of 25(OH)D in 120 patients was (40.2±16.0) nmol/L. There were 2 cases of vitamin D sufficiency (1.7%), 28 cases of vitamin D insufficiency (23.3%), and 90 cases of vitamin D deficiency (75.0%), of which 23 cases (19.2%) were of severe deficiency. 25(OH)D concentrations in patients with different lifestyles (indoors; indistinguishable indoors or outdoors; outdoors) were significantly different (35.3 nmol/L vs. 40.6 nmol/L vs. 49.5 nmol/L, F=8.274, P<0.001). Mean concentration of 25(OH)D in patients with sun exposure time of >30 min/d was higher compared to that in those with sun exposure time <30 min/d in the last month (46.4 nmol/L vs. 36.7 nmol/L, t=3.342, P=0.001). Multivariate linear regression analysis showed that the risk factors for 25(OH)D with statistical significance were Han ethnicity or not (β=-11.576, t=-1.991, P=0.049), housekeeping (including unemployment and retirement) or not (β=-6.136, t=-1.998, P=0.048), sun exposure time<30 min/d or none (β=-9.644, t=-2.829, P=0.006), body mass index (β=-2.056, t=-3.439, P=0.001) , and indoor degree of lifestyles (β=-4.419, t=-2.155, P=0.033). Conclusion Level of vitamin D is generally insufficient in patients with pulmonary tuberculosis in Shenzhen. It is necessary to strengthen health education related to vitamin D in patients with tuberculosis, especially in the high-risk population of vitamin D deficiency, such as in those with a lack of exposure to sunlight or high BMI.