Objective To reconstruct tissue-engineered uterine patch similar to native endometrium and myotrium. Methods The purified rabbit uterine smooth muscle cells and stromal cells were mixed with liquid type Ⅰ collagen, and laid on mold respectively. Then the collagen-embedded cells were combined to create a cell complex, epithelial cells were inoculated on top of the complex, histological and immunohistochemical staining, and scanning electron microscopy were used to analyze the engineered uterine tissue. Results The engineered uterine tissues (EUTs) were reconstructed with isolated and cultured uterine smooth muscle cells, stromal cells and epithelial cells. After cultured for 14 days, histological and immunohistochemical analyses showed that the smooth muscle cells and stromal cells in the EUTs distributed evenly in the two layers and the majority of the cells, with elongated nuclei, stretched along the stretching direction. The morphology of EUTs resembled that of the native uterine tissue. In scanning electron microscopy, some epithelial cells protruded pinopodes. The surface of epithelial cells was covered abundantly with microvilli and some cells were ciliated. Conclusion Uterine smooth muscle cells and stromal cells were mixed with Liquid type Ⅰcollagen respectively, and epithelial cells were inoculated on top of the complex for generation of EUTs similar to the native uterine tissue.

Working time of normal setting impression materials was 71 (hand mixing,30 s),66 (Alghamix,20 s) and 53 (Algimax-Ⅱ,8 s) seconds respectively.Working time of fast setting impression materials was 56 (hand mixing,30 s) and 51 (Alghamix 20 s) seconds respectively.Setting time of normal setting impression materials was 163 (hand mixing,30 s),160(Alghamix 20 s) and 124(Algimax-Ⅱ,8 s)seconds respectively.Setting time of fast setting impression materials were 131 (hand mixing,30 s) and121 (Alghamix 20 s) seconds.The working and setting time of normal setting impression materials mixed by hand mixing(30 s) and auto-mixing (Alghamix 20 s;Algimax-Ⅱ,8 s) and fast setting impression materials mixed by hand mixing(30 s) and with auto-mixing using Alghamix (20 s) may satisfly clinical requirement.

Thanks to the policies of resources to strengthen grassroots ,and innovative resource placement in Zhejiang province and the help of Zhejiang University School of Medicine ,Shaoxing regional medical center has achieved significant improvement in its medical capabilities .The cooperation features the following :active promotion of new medical ideas and key technologies ;overall enhancement of scientific and technological innovation ;talent training to advance disciplinary development ;and joint efforts to train postgraduates .The momentum ,however ,can only be maintained ,unless such problems as the means of resources placement ,disciplines alignment ,and medical workers development can be well addressed .

[Objective]To explore the application of alcohol in unearthed medical literature,so as to provide reference for the clinical application of alcohol in modern Chinese medicine.[Methods]Based on the unearthed literatures such as Wushier Bingfang,Wuwei Medical Bamboo Slips of Han Dynasty,ZHOU Jiatai Medical Bamboo Slips of Qin Dynasty,Tianhui Medical Bamboo Slips and so on,combined with the relevant records in the handed down literature,the application of alcohol in the unearthed literatures was compared and summarized.[Results]Although there is no specific reason for the use of alcohol in the unearthed medical literature,a comprehensive analysis can be made from the related records in the contemporaneous literature.The analysis showed that in the pre-Qin,Qin and Han Dynasties,most of the alcohol was yellow wine,which was used in the way of alcohol mixing,alcohol decoction and impregnation,and was widely used in the treatment of various diseases.It is concluded that the alcohol has the effect of"changing the medicinal properties,direct to the disease""warming the channels and clearing the collaterals,removing blood stasis and relieving pain""correcting the odor,enhancing the drug effect"and so on.The application of alcohol in the later literature showed different characteristics in each period,but all developed on the basis of the application of alcohol in the Qin and Han Dynasties.[Conclusion]Alcohol has great potential in the clinical treatment of modern Chinese medicine,but the soaking and decocting time of alcohol for medicine,the effect of different temperatures is worth further study.

Objective:To validate gender-related differences in patients with upper tract urothelial carcinoma (UTUC).Methods:We used a method of combination of SEER database analysis and validation in our center. We selected 2 125 men (57.8%) and 1 552 (42.2%) women who underwent radical nephroureterectomy (RNU) for UTUC between 1995 and 2015 within the surveillance, Epidemiology, and End Results registries (SEER). In male cases, the median age was 71(22-99)years old, median follow-up time was 53.0 (0-227) months, 902 (89.5%) cases were Caucasian, 1 384 cases (65.1%) were located in the renal pelvis, and 810(38.1%) cases were T 3-T 4. For female cases, the median age was 73.6(25-99)years old, median follow-up time was 53.1(0-226) months, 1 417(91.3%) cases were Caucasian, 1 043 cases (67.2%) were located in the renal pelvis, and 508 (32.7%) cases were T 3-T 4. The analysis of SEER database showed that female patients were older compared to male patients ( P=0.002), the proportion of T 3-T 4 was even lower ( P=0.028). There were no statistically significant differences in race, tumor location, and follow-up time between males and females (all P>0.05). We also enrolled 131 men (55.3%) and 106 women (44.7%) who underwent RNU for non-muscle invasive (T a/T is/T 1) UTUC between January 2000 and January 2015. These patients had no history of bladder cancer, UTUC and kidney transplantation. Preoperative cystoscopy was performed to confirm the absence of bladder tumor. The male group was (65.8±12.4)years old, with history of aristolochic acid medications in 7(5.3%) cases, 98 smoking cases (74.8%), and estimated glomerular filtration rate (eGFR) of (64.2±29.4)ml/(min·1.73 m 2). In the female group, mean age was (66.7±11.9)years, 14 (13.2%) cases had history of aristolochic acid medications, 16(15.1%) had history of smoking, eGFR (56.3±27.9) ml/(min·1.73m 2). Compared with female patients, male patients tended to had less aristolochic acids exposure (5.3% vs.13.2%, P<0.001), frequent smoking (74.8% vs. 15.1%, P<0.001) and better renal function ( P=0.036). The Kaplan-Meier test was used for time-to-event analysis. Univariate and multivariate logistic regression models were adopted to examine the effect of gender on the development of T 3-T 4 tumor. Univariate and multivariate Cox regression analyses were used to assess the roles of factors on overall survival (OS) in both SEER and cases in our center, and competing-risks regression model was used to assess the roles of factors on cancer-specific survival (CSS) in both SEER and cases in our center. Results:Multivariate logistic analysis showed that gendere represented an independent risk factor of T 3-T 4 UTUC development( OR=0.86, P=0.02). Kaplan-Meier analysis showed that better OS and CSS for females only existed in the non-muscle invasive stages(5-year OS rates were 80.4% vs.87.3%, χ 2=31.0, P<0.001; 5-year CSS rates were 82.6% vs.89.2%, χ 2=31.2, P<0.001). In multivariate competing-risks regression models, no statistically significant differences in survival were observed between males and females ( HR=0.83, P=0.115). For the patients in our center, there were also no statistically significant differences existed in the non-muscle invasive stage between two genders on OS and CSS ( HR=0.93, P=0.071; HR=0.87, P=0.064). Conclusions:Females were less likely to have advanced pathological T stage. The differences on OS and CSS between males and females only existed in non-muscle invasive stage. However, after accounting for gender related factors, gender no longer had effects on UTUC prognosis.

Objective:To compare the clinical efficacy and safety of intra-articular platelet rich plasma combined with hyaluronic acid and platelet rich plasma alone in the treatment of knee osteoarthritis.Methods:The relevant literatures published between January 2010 and December 2021 on the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid and injection of platelet rich plasma only in the treatment of knee osteoarthritis were searched. The bias risk of all the literatures included in the study was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The standardized mean difference ( SMD) was calculated for the difference of efficacy indexes, and the difference was compared by t- test. The odds ratio ( OR) was calculated for the difference of safety in-dex, and the difference was compared by t- test. Results:①A total of 7 relevant research literatures were in-cluded, all of which were in English. ②A total of 675 patients were included in the study, of which 330 patients were treated with intra-articular injection of platelet rich plasma and hyaluronic acid, and 345 patients were treated with intra-articular injection of platelet rich plasma only. ③The VAS scores of patients with platelet rich plasma and hyaluronic acid injection combined with injection and platelet rich plasma injection alone were compared. After 1 and 3 months of injection, the VAS scores of patients with platelet rich plasma combined with hyaluronic acid injection were compared with those of patients with platelet rich plasma injection only. There was no significant difference[ SMD(95% CI)=-0.02(-0.30, 0.27), t=-0.12, P=0.902; SMD(95% CI)=-0.40(-0.80, 0.00), t=-1.97, P=0.051]. After 6 months of injection, the VAS scores of patients with combined injection of platelet rich plasma and hyaluronic acid were significantly lower than those of patients with injection of platelet rich plasma only, and the difference was statistically significant [ SMD(95% CI)=-0.33 (-0.55, -0.11), t=-2.98, P=0.012]. ④The WOMAC scores of patients with combined injection of platelet rich plasma, hyaluronic acid and platelet rich plasma only were compared. After 12 months of treatment, the WOMAC scores of patients with combined injection of platelet rich plasma and hyaluronic acid were significantly higher than those of patients with PRP only, and the difference was statistically significant [ SMD(95% CI)=-0.30(-0.58, -0.03), t=-2.14, P=0.033]. ⑤The incidence of adverse events of platelet rich plasma combined with hyaluronic acid was lower than that of platelet rich plasma only [ OR(95% CI)=0.55(0.33, 0.93), P=0.021]. Conclusion:Compared with intra-articular injection of platelet rich plasma only, the short-term clinical efficacy of combined injection of platelet rich plasma and hyaluronic acid is equivalent to that of injection of platelet rich plasma only, but the long-term clinical efficacy is significantly better, and the safety of combined injection of platelet rich plasma and hyaluronic acid is significantly better.

OBJECTIVETo explore the role of sphingomyedlin phosphodiesterase 1 (SMPD1) gene mutations in the pathogenesis of Parkinson's disease (PD).

METHODSFor 110 Chinese patients with PD, all exons of the SMPD1 gene were sequenced, and the results were compared with reference sequence from GenBank to identify possible mutations.

RESULTSA novel heterozygous mutation Ex2:c.677C>A/p.P226Q (likely pathogenic) was identified in a patient, which resulted in substitution of Glutamic acid by Proline at position 226. In addition, two known single nucleotide polymorphisms (SNPs) Ex1:c.107T>C/p.V36A (benign) and Ex6:c.1522G>A/p.G508R (benign), and three previously reported SMPD1 mutations Ex2:c.T371T>G/p.L124R (uncertain significance), Ex2:c.636T>C/P.(=)(benign) and Ex6:c.1598C>T/p.P533L (uncertain significance) were identified. The novel p.P226Q mutation and p.P533L mutation were predicted to have a possibly damaging effect on the structure and function of SMPD1 protein, which in turn may lead to PD.

CONCLUSIONThe mutation rate of the SMPD1 gene was 3.64% among Chinese PD patients. Genetic variants of SMPD1 may increase the risk of PD.

Open and percutaneous pedicle screw insertion would have the risk of damaging the nerve or blood vessels,due to the complexity of the spine structure.Despite the aid of various means of preoperative CT and intraoperative navigation,pedicle screw insertion failure rate is still 4.1％-28.9％.In recent years,the development of spine surgical robots might bring new solutions to this problem.The use of the spine surgical robots has been more than 20 years,and developed rapidly with the development of intraoperative navigation and intraoperative CT in recent years.Some robots have been certified by the FDA or the CE.And the number of reported robot-assisted surgeries such as scoliosis surgeries or severe lumbar spondylolisthesis surgeries has increased rapidly as well.Current literatures have verified the robot-assisted pedicle screw insertion has high accuracy,good stability and short learning curve,which may be able to become one of the main trend of spinal surgery in the future.This article mend to review some developed spine surgery robot and their clinical application indication and results.

Objective To investigate the regulatory mechanism of Paraquat (PQ)-induced epithelial-mesenchymal transition (EMT) and the protective mechanism of N-acetyl-cysteine (NAC) in PQ-induced A549 cells by EMT markers (E-cadherin and α-smooth muscle actin).Methods EMT model was established by 30 μmol/L PQ-exposed A549 cells for 4 d.The application of 10 mmol/L NAC was incubated with A549 cells for 2 h in advance.Morphological changes of A549 cells were observed under light microscope.Western blot was used to detect the expression levels of TGF-β1,E-cadherin and α-smooth muscle actin.Results In PQ-induced EMT model,the PQ group showed typical morphological changes,and the cells changed from cobblestone-like epithelial appearance to spindle-shaped mesenchymal-like appearance compared to the control group.Westem blotting showed that the protein levels of TGF-β1 and α-smooth muscle actin in the PQ group were significantly increased and the protein levels of E-cadherin were decreased in the PQ group (all P＜0.05).NAC preincubation can effectively reverse the above changes caused by PQ exposure:the protein levels of E-cadherin and α-smooth muscle actin were significantly increased and decreased,respectively and morphological changes showed more cobblestonelike epithelial appearance.Conclusion Cell experiments showed that PQ exposure can cause EMT in epithelial cells,and NAC has a protective effect in this process.Thus,it may provide new ideas and strategies for the treatment of pulmonary fibrosis caused by PQ poisoning in clinical practice.

This paper introduced the development of medical specialists alliance in Zhejiang University. With Jinhua Central Hospital as an example,merits and setbacks of the 3-level trusteeship model in practice were discussed,with improvement recommendations raised for progress of the hierarchical medical system.