Objective:To prepare a bone substitute using microsphere scaffold containing adiponectin(APN)and to investigate the release behavior of the scaffold in vitro.Methods:Chitosan microsphere was developed by an emulsion-ionic cross-linking method. Poly (L-lactic-co-glycolic)acid (PLGA)and β-tricalcium phosphate (β-TCP)were used to prepare microsphere scaffold containing APN.The morphology,particle size,drug loading,incorporation efficiency and release behavior of the microsphere were examined. Results:The APN containing microsphere showed good spherical geometry,suitable size and microporosity under scanning electron microscope.The average diameter of the milipore was 20 -200 μm;the drug loading and incorporation efficiency were 1 .3% and 70.3% respectively.The controled-release process continued for 91 days.The extract solution from the APN microsphere-scaffold promoted MC3T3 cell proliferation without cytotoxicity.Conclusion:The APN microsphere-scaffold has sustained release function and may promote osteoblast proliferation.

Objective To study the association of prevalence of cardio-cerebro vascular diseases (CCVD) with metabolic syndrome (MS) defined by different criteria in middle and aged people.Methods A cross-section survey was conducted among 1458 people aged 55 years and over in urban and rural areas of Beijing in 2009.MS definitions by World Health Organization (WHO),National Cholesterol Education Program-Adult Treatment Panel Ⅲ (NCEP-ATP Ⅲ ) revised,international diabetes mellitus (IDF) and Chinese Diabetes Society (CDS) were applied to analyze the association MS with the prevalence of CCVD.Results The risks of CCVD were all significantly higher in patients with MS than with non-MS using 4 definitions of MS.The definitions of WHO and CDS showed well agreement with the prevalence of CCVD.OR values of MS for CCVD were 2.14 folds (95％ CI:1.59-2.87) for WHO definition and 1.91 folds (95％ CI:1.43-2.55) for CDS definition,while OR values of MS for CCVD were 1.68 folds (95％ CI:1.32-2.15) for NCEP-ATPⅢ definition and 1.64 folds (95％ CI:1.26-2.13) for IDF definition as compared to non-MS,respectively.After adjustment for age,sex,region,history of smoking and alcohol drinking,the OR values in above four definitions were 1.91,1.88,1.67 and 1.80,respectively.The OR value of MS was highest for stroke by CDS definition and highest for coronary heart disease by WHO definition.Conclusions MS values defined by WHO and CDS are the optimal index of prevalence for CCVD in middle and aged people.

Objective:To analyze the prognosis of hepatocellular carcinoma (HCC) patients with thrombocytosis (platelet count ≥350×10 9) after transcatheter arterial chemoembolization (TACE), and the effect of thrombocytosis on the prognosis of patients with HCC after TACE. Methods:Clinical data of 867 patients with HCC admitted to the Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2013 to May 2018 were retrospectively analyzed. After propensity score matching, 99 patients were enrolled, including 70 males and 29 females, aged (60.1±12.1) years. Patients were divided into the groups with thrombocytosis ( n=33) and without thrombocytosis ( n=66). The gender, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, and total bilirubin were compared between the two groups. The association of thrombocytosis with the prognosis of HCC after TACE treatment were analyzed using univariate and multivariate Cox regression. Results:After propensity score matching, the male proportion, maximum tumor diameter, BCLC stage, and serum level of total bilirubin were comparable between the groups (all P>0.05). Before TACE treatment, the platelet count of patients with thrombocytosis was (394.4±54.5)×10 9/L, which was higher than that after TACE [(278.2±86.4)×10 9/L, t=7.63, P<0.001]. The progression-free survival rates after TACE in without thrombocytosis group were 83.3%, 24.2%, and 7.6% at 3, 6 and 9 months, respectively, better than those in thrombocytosis group (51.5%, 3.0%, and 3.0%, respectively; χ2=31.24, P<0.001). The overall survival rates after TACE in without thrombocytosis group were 81.8%, 30.3%, and 4.5% at 1, 2 and 3 years, respectively, better than those in thrombocytosis group (15.2%, 9.1%, and 3.0%, respectively; χ2=27.89, P<0.001). Multivariate Cox regression analysis showed that patients of HCC with thrombocytosis had an increased risk of tumor progression ( HR=5.785, 95% CI: 3.291-10.168, P<0.001) and increased risk of death ( HR=4.090, 95% CI: 2.482-6.740, P<0.001) after TACE. Conclusion:The prognosis of TACE for HCC might be worse in patients with thrombocytosis. Thrombocytosis is a risk factor for cumulative survival and progression-free survival of HCC patients after TACE.

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.

ObjectiveTo study the relationship between the exposure to two kinds of phthalate esters （PAEs） ［Di-N-butyl phthalate，（DBP） and Di-（2-ethylhexyl）phthalate （DEHP）］ and estrogen homeostasis in pregnant women. MethodsIn 2021， we classified the Jiading District of Shanghai into five geographical areas， east， west， south， north and central. A total of 151 pregnant women from each area were selected for questionnaire survey， with random urine samples during first， second， and third trimesters collected. A DBP metabolite ［Mono-N-butyl phthalate （MBP）］ and two DEHP metabolites ［Mono（2-ethylhexyl） phthalate （MEHP）， Mono（2-ethyl5-oxohexyl） phthalate， （MEOHP）］ and three estrogens ［estrone （E₁）， 17β -estradiol （E₂）， and estriol （E₃）］ in urine were determined by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry. After a natural logarithmic transformation of PAEs metabolite levels and estrogen concentration， multivariable linear regression was used to control potential confounders and determine the relationship between PAEs metabolite levels and estrogen concentration. ResultsThe detection rates of three PAEs metabolites in urine of pregnant women were more than 98%. The median corrected concentrations of MBP， MEHP and MEOHP were 5.18， 0.59 and 4.23 mg·kg^-1， respectively. During the whole pregnancy， MEOHP was positively correlated with E₁ （β=0.450， 95%CI： 0.057‒0.844）， and MBP was positively correlated with E₃ （β=0.250， 95%CI： 0.034‒0.465）. Stratified by trimesters， MBP was positively correlated with E₃ in the first trimester （β=0.428， 95%CI： 0.103‒0.752）. MEOHP was positively correlated with E₁ in the second trimester （β=0.734， 95%CI： 0.130‒0.752）， and had a possitive trend with E₁ in the third trimester （β=0.744， 95%CI： -0.140‒1.629）. In addition， MEHP had a negative correlation with E₁ in the second trimester （β=-0.498， 95%CI： -1.063‒0.066）. MEOHP had a positive correlation trend with E₂ （β=0.628， 95%CI： -0.101‒1.356） in the third trimester. ConclusionPAEs exposure may interfere with estrogen homeostasis during pregnancy and differs by trimesters. Given the cross-sectional nature of this study， it warrants further study to validate the findings.

An ultimate goal of neuroscience is to decipher the principles underlying neuronal information processing at the molecular, cellular, circuit, and system levels. The advent of miniature fluorescence microscopy has furthered the quest by visualizing brain activities and structural dynamics in animals engaged in self-determined behaviors. In this brief review, we summarize recent advances in miniature fluorescence microscopy for neuroscience, focusing mostly on two mainstream solutions - miniature single-photon microscopy, and miniature two-photon microscopy. We discuss their technical advantages and limitations as well as unmet challenges for future improvement. Examples of preliminary applications are also presented to reflect on a new trend of brain imaging in experimental paradigms involving body movements, long and complex protocols, and even disease progression and aging.

BACKGROUND: Immune checkpoint inhibitor monotherapy is reported to have little effect in advanced non-small cell lung cancer (NSCLC) patients with driver oncogenes. However, recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy after tyrosine kinase inhibitors (TKIs) drug resistance. The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor (EGFR) sensitive mutation, and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation. METHODS: A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital, Capital Medical University from June 2018 to November 2020 were collected. After the progress of targeted therapy, they had received programmed cell death protein 1 (PD-1) checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy. RESULTS: Of the 27 advanced NSCLC patients, 19 cases (70.4%) did not have T790M mutation. There were 8 cases (29.6%) with T790M point mutation. The total objective response rate (ORR) was 40.7%. Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations (χ²=4.15, P=0.230). But progression-free survival (PFS) was significantly longer in patients without T790M mutation than in patients with T790M mutation (9.2 mon vs 3.3 mon, χ²=2.808, P=0.041), and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor (12.2 mon vs 7.3 mon, χ²=3.22, P=0.062). ORR of patients without T790M was significantly better than that with T790M (52.63% vs 12.5%, P=0.045). CONCLUSIONS Patients with EGFR mutation can benefit from later-line combined immunotherapy. The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line. Therefore, the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.

Objective: To observe the parameters of the results of suppression head impulse paradigm (SHIMP) in healthy adults, and to provide reference for evaluating vestibular oculomotor reflex function in patients with peripheral vertigo. Methods: Fifty healthy adults, 22 males and 28 females, aged from 23-65 years, with an average age of (38.5±11.6) years, were recruited from January to March 2018. Parameters provided by the video head pulse software included the gains, the latency and the peak velocity of saccades, and comparison was made with head impulse paradigm (HIMP). Results: All subjects were elicited anti-compensatory saccades in SHIMP. The normal values of left and right gains were 1.02 and 1.10 in HIMP, and 0.93 and 1.01 in SHIMP respectively. The left and right saccades latency were (201.1± 50.8)ms and (187.0± 42.9)ms, and the peak saccadic velocity were (302.7±58.5)°/s and (291.5±46.5)°/s in SHIMP; there were small but significant difference between two sides about gains in HIMP and SHIMP, as well as latency in SHIMP(P<0.05); there were small but significant difference between HIMP and SHIMP about gains in ipsilateral(P<0.01); there were no significant difference between two sides about peak saccadic velocity in SHIMP(P>0.05). Conclusions SHIMP can be used for the examination of vestibular oculomotor reflex function in adult population. It is easy to be operated and is convenient for clinical application. Combined with head pulse test, the function of the semicircular canal can be evaluated together.