Knee Osteoarthritis is one of the most common degenerative diseases.Although the morbidity of knee osteoarthritis increases dramatically,there is no effective medication that can repair the damaged articular cartilage and restore the joint function.Recently,with the technical development of cell transplantation and regulation,more attentions have been paid in this area.The techniques included osteochondral autograft transplantation,mosaicplasty,chondrocytes based matrix-induced autologous chondrocyte implantation,and mesenchyma stem cells based cell therapy.The study of cell differentiation is also more in-depth.It has been confirmed that all of these methods can alleviate the symptoms and improve the function of knee osteoarthritis to some extent.Stem cell therapy seems have greater advantage than other intervention.Massive chondrocytes can be gained through induction and culture of mesenchyma stem cells in vitro,and regenerated cartilage could be found on the surface after delivering stem cells into knee joint through a certain way.These technologies are hopeful to prevent from knee osteoarthritis or even reverse the progress of it at early stage.However,there are a variety of problems about in vitro cell transplantation,such as the unknowing regulation of mesenchyma stem cells,the difficulty of keeping the characteristic stability of new born chondrocytes,the integrity of new cartilage tissue and the way chondrocytes delivered.Cell therapy has been applied both in basic research and in clinic trials.The present review is focused in the current progress of cell therapy in knee osteoarthritis and discuss the challenges and troubles.Furthermore,we also summarize a series of ongoing clinical trials,and try to find out the exact clinical effects of cartilage repair by using cell therapy.

Objective To compare the effects of patient's tolerance to laryngeal mask airway (LMA) and tracheal tube (TT) on the appropriate level of sevoflurane anesthesia.Methods Eighty ASA Ⅰ or Ⅱ patients aged 30-60 yr weighing 50-70 kg undergoing elective thyroid or breast surgery were randomly divided into 2 groups (n=40 each):LMA group and TT group.Anesthesia wag induced with propofol 1.6mg/kg,fentanyl 3μg/kg and recuronium 0.6mg/kg.LMA or tracheal tube was inserted,and the patients were mechanically ventilated.Anesthesia was maintained with inhalation of 1.5%-3.0% sevoflurane and 50% N2O in O2 in group LMA,and with 2.5%-5.0% sevoflurane and 50% N2O in O2 in group TT.The flow of O2 and N2O was 0.7-1.0L/min,and the concentration of sevofluranee was adjusted to maintain AAI at 15-25.ECG,HR,MAP,SpO2,PETCO2,AEP and end-tidal sevoflurane concentration were continuonsly monitored.The end-tidal sevoflurane concentration was recorded at 1,5 and 10 min after LMA/TT was placed (T1-3),at 1h after skin incision (T4) and at the end of operation before removal of LMA or extubation (T5).The recovery time of consciousness,adverse cardiovascular events and adverse reactions were recorded.Results The end-tidal sevoflurane concentration was significantly lower,the recovery time of consciousness and removal of LMA or extubation time were shorter,and the incidence of adverse cardiovascular events and adverse reactions was lower in LMA group than in TT group.Conclusion At the same depth of anesthesia (AAI 15-25),sevoflurane concentration is significantly lower in LMA group than in TT group,with fewer complications and smaller cardiovascular reaction.

ObjectiveTo explore the efficacy of sevoflurane or propofol combined with remifentanil during the maintenance of general anesthesia in thyroid gland surgery.MethodsSixty patients underwent thyroid gland surgery were randomly divided into tow groups.Once the larynx mask was intubated, anesthesia was maintained with propofol(the effect site concentration was 2.5 ～3.5mg/L) and remifentanil(the effect site concentration was 4.5 ～5.5μg/L) by TCI technique in group P,but with sevoflurane(2％～4％) and remfentanil(the effect site concentration was 2.5 ～4.0g/L)in group S.The depth of anesthesia was measured by the A-line TM AEP Monitor which expressed as A-Line ARX Index TM(AAI).All patients' SBP,DBP and HR were recorded at eight time points: before induction time(T0) ,after induction but before larynx mask intubation time(T1) ,intubate larynx mask time(T2) ,cut skin time (T3), separate thyroid gland time (T4), cut thyroid gland time (T5), remove larynx mask time (T6) ,leave the operation room time(T7).The emergency time,the conscious of the patients after anesthesia and the side effects were also recorded.ResultsThere were no significant differences between the groups with respect to age,gender,weight,the duration of operation,the emergency time and the conscious of the patients after anesthesia.SBP,DBP,HR of the patients in both groups showed no significant difference at T0,T1 ,T2, T3 (all P ＞ 0.05), but had significant difference at T4,T5,T6, T7 (all P ＜ 0.05).Compare with group P,the incidentce of restlessness, dizziness, drowsiness, rigor and pain was significantly lower in group S(all P ＜0.05).The incidentce of nausea,vomit and aspiration did not appear in both groups.ConclusionBoth groups showed good anesthesia effects and the patients also emerged from anesthesia quickly.But the anesthesia maintained with sevoflurane and remifentanil could bring more stable hemodynamics and lower incidence rate of the side effects.

Objective To evaluate the effect of awake tracheal intubation with intubating larynegeal mask airway (ILMA) on stress responses of hypertensive patients.Methods Sixty hypertensive patients,aged 45-64 yr,with body mass index of 20.3-27.5 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective abdominal surgery under general anesthesia,were divided into 2 groups (n=30 each) using a random number table:direct laryngoscope group (group D) and ILMA group (group I).At 3 min after topical anesthesia (T1),while epiglottis and glottis were exposed with direct laryngoscope in group D or during ILMA insertion in group I (T2),immediately after completion of intubation (T3),when the maximum change in hemodynamics after intubation appeared (at about 15 s after tracheal tubes were placed,T4),and at 5 min after completion of intubation (T5),mean arterial pressure (MAP) and heart rate (HR) were recorded,and blood samples were collected for determination of plasma epinephrine concentrations by radio-immunity method.Successful intubation at first attempt was recorded.Results Compared with the parameters at T1,the MAP,HR and plasma epinephrine concentrations were significantly increased at T2-4 in group D (P＜0.01),and no significant change was found in the parameters mentioned above at the other time point in group I (P＞0.05).Compared with group D,the MAP,HR and plasma epinephrine concentrations were significantly decreased at T2-4 (P＜0.01),and no significant change was found in the success rate of intubation at first attempt in group I (P＞0.05).Conclusion Awake tracheal intubation with ILMA does not induce strong stress responses and is helpful in avoiding the occurrence of cerebrovascular accidents,thus increasing the safty of awake tracheal intubation in hypertensive patients.

Objective To evaluate the effect of age on the median-effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the patients.Methods Ninety adult patients of both sexes,of ASA physical status Ⅰ or Ⅱ,with body mass index 19-25 kg/m2,scheduled for elective gastroscopy,were divided into 3 groups according to age (n =30 each):18-39 yr group (Ⅰ group),40-64 yr group (Ⅱ group) and 65-85 yr group (Ⅲ group).In Ⅰ,Ⅱ,Ⅲ groups,propofol was given by target-controlled infusion with the initial target concentrations of 2.5,2.0 and 1.5 μg/ml,respectively,and gastroscopy was performed when the target concentration was achieved.Body movement was defined as the directional movement in head or four extremities during gastroscopy.The target plasma concentration of propofol was determined by up-and-down sequential trial.Each time the plasma concentration of propofol increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ confidence interval) of propofol was 4.2(3.8-4.5),4.1(3.7-4.4) and 2.4(1.8-2.7) μg/ml in Ⅰ,Ⅱ and Ⅲ groups,respectively.There was no significant difference in the EC50 of propofol between group Ⅱ and group Ⅰ.The EC50 of propofol was significantly lower in group Ⅲ than in Ⅰ and Ⅱ groups.Conclusion Age affects propofol-induced analgesia in patients with visceral pain,and the potency of propofol inhibiting visceral pain during gastroscopy in the elderly patients is significantly enhanced as compared with that in the young and middle-aged patients.

ObjectiveTo investigate the changes in positive staining of CD34, CK7, and CK19 and amount of fibrous collagen deposition in patients with chronic hepatitis B (CHB) and the pathological basis affecting FibroTouch measurements. MethodsA retrospective analysis was performed for the clinical data of 72 CHB patients who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2015 to December 2017. The amount of positive immunohistochemical staining of CD34, CK7, and CK19 was calculated, as well as the amount of fibrous collagen deposition in Masson trichrome staining and liver stiffness measurement (LSM) by FibroTouch. The t-test was used for comparison of normally distributed continuous data between two groups. The Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of ranked data between multiple groups. The receiver operating characteristic (ROC) curve was used to analyze the value of LSM in the diagnosis of hepatitis B cirrhosis, and the logistic regression model was used for multivariate analysis. ResultsWith the increase in inflammation degree, there was no significant change in the amount of positive staining of CD34 (P＞0.05), while there were significant increases in the amount of positive staining of CK19 and the amount of fibrous collagen deposition (H=9.02 and 14.12, P=0011 and 0.001). With the progression of liver fibrosis, there were significant increases in the amount of positive staining of CD34 and CK7 and the amount of fibrous collagen deposition (H=10.26, 16.29, and 22.97, P=0.016, 0.001, and ＜0.001). The logistic regression analysis showed that the amount of positive staining of CK7 (Wald=4.756, P=0.029) and the amount of fibrous collagen deposition (Wald=4.757, P=0.029) were independent influencing factors for FibroTouch measurements. ConclusionIncreases in the amount of fibrous collagen deposition and the amount of positive staining of CK7 may lead to increased FibroTouch measurements.

Objective To investigate the prevalence and risk factor of Ofloxacin resistance among the tuberculosis patients in Shanghai.Methods Totally 447 isolates resistant to anyone of first-line drug (Isoniazid,Rifampicin,Streptomycin and Ethambutol) and 151 randomly selected isolates susceptible to all above drugs were collected from district tuberculosis(TB) hospitals in Shanghai during 2009 to 2010.All 598 isolates were subject to Ofloxacin sensitive test.Logistic regression analysis was conducted to determine risk factors of Ofloxacin resistance.DNA sequencing was applied to study the mutation characteristics in gyrA and gyrB among Ofloxacin resistant isolates.Results Seventy-two(16.1%) of the 447 drug-resistant isolates were found resistant to Ofloxacin,and the Ofloxacin resistant rate among multiple drug-resistant (MDR) isolates was 39.6%(44/111).Ofloxacin resistance was also found in 4(2.6%) of the 151 drug sensitive isolates.Logistic regression analysis showed that first-line drug-resistance MDR(resistant to at least rifampin and isoniazid) and poly-drug resistance(resistance to two or more first-line drugs but not MDR) had significant effect on Ofloxacin resistance(OR = 19.5、5.6,95% CI:6.4 - 59.4、1.7 - 18.1,all P＜ 0.05);re-treatment(OR = 2.3,95 % CI:1.2 -4.0,P＜ 0.05),and a higher age(OR = 1.03,95 % CI:1.0 1 - 1.05,P＜ 0.05)were also significantly associated with Ofloxacin resistance.Resistance mutations in the gyrA and gyrB genes were detected in 62 of 76(81.6%) isolates with phenotypic Ofloxacin-resistance. Conclusions The Ofloxacin resistance rate in Shanghai MDR-TB patients is significantly higher than the pan-susceptible TB patients.Risk factors of ofloxacin resistance are MDR,poly-resistant,retreated patients,age.Among them,MDR has the highest strength of association.

Objective To develop the technique to detect total core antigen of HCV(Total HCV-cAg) by Enzyme-Linked Immu-nosorbent Assay (ELISA) and apply it for clinical diagnosis. Methods 201 serum samples with anti-HCV antibody were detected total HCV-cAg after pre - treating the samples, then the sensitivity of results were compared with HCV RNA tests. Among them, 176 cases was determined by FQ-PCR, and 25 cases by RT-PCR for HCV-RNA. Results HCV RNA was found in sera from 88 of 201 samples (43.8%). Total HCV-cAg was positive in 71 (35.3%) of 201 samples . There was no significant difference between the detection rate of HCV RNA by PCR and total HCV-cAg by ELISA. Conclusion Detection of total core antigen of HCV is suitable to be used as to diagnose HCV in clinic.

Objective:To explore the correlation between SAM domain and HD domain-containing protein 1 (SAMHD1) and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma.Methods:The expression of SAMHD1 in lung adenocarcinoma and its effect on prognosis were analyzed by online database GEPIA and Kaplan-Meier Plotter. The expression of SAMHD1 in lung adenocarcinoma cell lines was detected by quantitative real-time PCR (qPCR) and Western blotting. SAMHD1 gene was silenced in H1975, H1299 and LLC cells by small interfering RNA transfection and lentivirus infection, respectively. The mRNA and protein expression levels of PD-L1 in lung adenocarcinoma cells of control group, siSAMHD1-1 group and siSAMHD1-2 group were detected by qPCR and Western blotting. The membrane PD-L1 level was detected by flow cytometry. A mouse lung adenocarcinoma xenograft model was constructed. The PD-L1 levels in the tumor tissues of control group and shSAMHD1 group were detected by immunohistochemistry. Cell proliferation activities of the control, siSAMHD1-1 and siSAMHD1-2 groups were detected by CCK-8 assays.Results:The GEPIA database results showed that the mRNA expression of SAMHD1 in lung adenocarcinoma was lower than that in normal lung tissue (4.81±0.90 vs. 5.99±0.76, t=20.67, P<0.001) . The median overall survival time of patients with high SAMHD1 expression was significantly longer than that of patients with low SAMHD1 expression (109.0 months vs. 87.7 months, χ2=26.83, P=0.002) . The relative mRNA expression levels of SAMHD1 in A549, PC9, H1299 and H1975 cells were 1.00±0.02, 0.75±0.05, 3.49±0.19 and 7.25±0.38 ( F=589.00, P<0.001) , and the relative protein expression levels were 1.00±0.06, 0.34±0.07, 1.67±0.22 and 2.11±0.63 ( F=15.79, P=0.001) . In H1975 cells, the relative mRNA levels of PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 1.00±0.00, 1.54±0.26 and 2.89±0.13 ( F=102.30, P<0.001) , and the relative protein expression levels were 1.00±0.01, 1.50±0.10 and 1.52±0.33 ( F=6.65, P=0.030) . In H1299 cells, the relative mRNA levels of PD-L1 in the three groups were 1.00±0.08, 1.63±0.03 and 2.14±0.03 ( F=368.80, P<0.001) , and the relative protein levels of PD-L1 were 1.00±0.07, 1.88±0.35 and 2.05±0.38 ( F=10.66, P=0.011) . The expression level of PD-L1 in the siSAMHD1-1 and siSAMHD1-2 groups was higher than that in the control group (all P<0.05) . Flow cytometry results showed that in H1975 cells, the fluorescence intensity of membrane PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 246.83±27.59, 325.60±8.00 and 308.93±7.60 ( F=17.56, P=0.003) , and in H1299 cells, the fluorescence intensity of membrane PD-L1 in the three groups were 959.00±6.25, 1 084.33±7.64 and 1 085.33±21.22 ( F=86.74, P<0.001) . The fluorescence intensity of PD-L1 in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . In xenograft mouse model, the H-SCORE of PD-L1 in the shSAMHD1 group was higher than that in the control group (7.99±1.10 vs. 4.49±0.43, t=5.13, P=0.007) . The proliferative activities of H1975 cells in the control group, siSAMHD1-1 group and siSAMHD1-2 group at 72 h were 0.50±0.02, 0.75±0.05 and 0.73±0.06 ( F=25.01, P=0.001) . The proliferative activities of H1299 cells in the three groups at 72 h were 0.80±0.01, 1.00±0.04 and 0.93±0.07 ( F=13.90, P=0.006) . The cell proliferation activity in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . Conclusion:SAMHD1 silencing induces PD-L1 expression in lung adenocarcinoma.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.