Minocycline is the second generation semisynthetic tetracycline antibiotics.A variety of animal models and clinical trials have shown that it has neuroprotective effect.Its mechanism is associated with inhibiting apoptosis, alleviating inflammatory reaction, reducing infarct volume, and alleviating vascular injury.This article reviews the neuroprotective effect of minocycline in preclinical phase and early clinical trials of acute ischemic stroke.

BACKGROUND:The establishment of a safe, reliable and easily repeatable mouse model of nonalcoholic fatty liver disease is the prerequisite for the study of the diagnosis and treatment of the disease.
OBJECTIVE:To establish a C57BL/6 mouse model of nonalcoholic fatty liver disease and observe changes of biochemical indicators, which can provide a theoretical basis for its pathogenesis and drug treatment.
METHODS:Sixty healthy male C57BL/6 mice were randomly divided into a control group of 30 cases (normal diet), and a model group of 30 cases (high fat diet). Models of nonalcoholic fatty liver were established. At 8 weeks, body mass, liver index, and homogenate superoxide dismutase activity in the liver were detected. Changes in serum alanine aminotransferase, aspartate aminotransferase, triglyceride glycerol, cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observed. Pathological examination was performed.
RESULTS AND CONCLUSION:(1) Pathological sections showed that large droplets and smal lipid droplets in the mouse liver and spread the whole liver. Swel ing of the liver cel s, visible cytoplasmic vacuoles and obviously inflammatory changes in liver cel s were observed in the model group. (2) Body weight and liver index were significantly higher in the model group than in the control group (P<0.05). Superoxide dismutase activity was significantly reduced in the liver (P<0.05). (3) Triglycerides, cholesterol, and low-density lipoprotein cholesterol levels were significantly higher, but high-density lipoprotein cholesterol levels were significantly lower in the model group than in the control group (P<0.05). (4) Nonalcoholic fatty liver mouse model is ideal for high-fat diet-induced animal model. The method is simple, repetitive, and can provide a stable animal model for the study on the mechanism of nonalcoholic fatty liver disease and drug treatment.

Objective:To investigate the correlation between heart rate variability (HRV) and cerebral small vessel disease (CSVD) in patients with obstructive sleep apnea (OSA).Methods:Patients with OSA received polysomnography and brain MRI examination in Weihai Municipal Hospital from July 2019 to July 2020 were consecutively collected for cross-sectional analysis. The 5 min HRV before sleep (awake state) was analyzed. The patients were divided into CSVD group and non-CSVD group according to the overall burden of CSVD. The demographic data, clinical data, polysomnography parameters and HRV time domain and frequency domain parameters were compared between the two groups. Multivariate logistic regression analysis was used to determine the correlation between the HRV parameters and CSVD in patients with OSA. Results:A total of 100 patients with OSA were enrolled, including 79 males (79.0%), aged 52.36±8.66 years, apnea hypopnea index (AHI) 38.70±24.65/h. There were 46 patients (46.0%) in the CSVD group and 54 (54.0%) in the non-CSVD group. Univariate analysis showed that there were significant differences in age, AHI, oxygen desaturation index (ODI), percentage of blood oxygen saturation <90% in total sleep time (T90), square root of the mean of the sum of the squares of the difference between adjacent RR intervals (RMSSD), power in high frequency range (HF), power in low frequency range (LF) to HF ratio (LF/HF) between the CSVD group and the non-CSVD group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for age, body mass index, systolic blood pressure, AHI, ODI, and T90, RMSSD (odds ratio 0.625, 95% confidence interval 0.389-0.981; P=0.041) and LF/HF ratio (odds ratio 1.429, 95% confidence interval 1.011-2.020; P=0.043) were the independent influencing factors of CSVD in patients with OSA. Conclusion:Increased LF/HF and decreased RMSSD in OSA patients with CSVD suggest that the increased sympathetic excitability and decreased vagus function, which may be one of the pathophysiological mechanisms of occurring CSVD in patients with OSA.

Objective:To investigate the correlation between heart rate variability (HRV) and cognitive impairment in patients with obstructive sleep apnea (OSA).Methods:Patients received polysomnography in Weihai Municipal Hospital from June 2019 to November 2020 were enrolled as the subjects of cross-sectional analysis. According to the Montreal Cognitive Assessment score, the patients with OSA were divided into a cognitive impairment group and a non-cognitive impairment group. Multivariate logistic regression analysis was used to determine whether HRV parameters were the independent influencing factors of cognitive impairment in patients with OSA. Multiple linear regression analysis was used to determine the independent correlation between HRV parameters and overall cognition as well as each cognitive domain in patients with OSA. Results:A total of 115 patients with OSA were included, including 80 males (69.6%), aged 58.25±9.88 years. Among them, there were 61 in the cognitive impairment group (53.0%) and 54 in the non-cognitive impairment group (47.0%). The standard deviation of the R-R interval in normal sinus beats (SDNN), the square root of the mean of the sum of the squares of the difference between adjacent NN intervals (RMSSD), the percentage of the number of pairs of adjacent R-R intervals differing by more than 50 ms (pNN50) and the power in high-frequency range (HF; 0.15-0.40 Hz) in the cognitive impairment group were significantly lower than those in non-cognitive impairment group (all P<0.05). Multivariate logistic regression analysis showed that SDNN (odds ratio [ OR] 0.551, 95% confidence interval [ CI] 0.380-0.798; P=0.002), RMSSD ( OR 0.516, 95% CI 0.342-0.779; P=0.002), pNN50 ( OR 0.900, 95% CI 0.834-0.971; P=0.006), LF ( OR 0.821, 95% CI 0.687-0.982; P=0.030) and HF ( OR 0.687, 95% CI 0.525-0.899; P=0.006) were the independent protective factors of cognitive impairment in patients with OSA. Multiple linear regression analysis showed that SDNN ( β=0.208, P=0.023), RMSSD ( β=0.228, P=0.011), pNN50 ( β=0.186, P=0.040), HF ( β=0.235, P=0.010) is independently correlated with overall cognitive function in patients with OSA. Conclusion:The decline of HRV parameters SDNN, RMSSD, pNN50 and HF is independently correlated with cognitive impairment in patients with OSA, suggesting that the decline of vagus nerve function may be involved in the mechanism of cognitive impairment in patients with OSA.

Peripheral blood circulating tumor DNA(ctDNA) is a kind of DNA that is released into the blood circulation system after the tumor cell somatic cell DNA is exfoliated or when the cell apoptosis is released.ctDNA is a characteristic tumor biomarker, known as " liquid biopsy" . It can reflect the invasion and metastasis of the tumor, and can monitor the effect and prognosis of the tumor.The current research is mainly focused on relatively mature breast cancer, lung cancer and other diseases.In this study, the development of ctDNA inspection technology and its current research status at home and abroad are reviewed.

Objective To compare the effect of two procedures,named "mucosa to mucosal "and "end-inside" anastomosis for cholangiojejunostomy,and analyze its applicable scope.Methods A retrospective analysis was performed on the clinical data of 340 patients who underwent choledochojejunostomy from May 2012 to May 2017 in the Navy General Hospital.These patients were divided into two groups according to the procedure they received,including " mucosa to mucosal" anastomosis (n =249) and " end-inside"anastomosis (n =91).Two anastomotic methods of intraoperative state and postoperative complications were compared respectively under normal bile duct condition and cholangiectasis condition.Results When the common bile duct was not dilated,time spent for anastomoting in "end-inside" anastomosis was significantly shorten than that in "mucosa to mucosal" anastomosis (12.7 ± 1.2) min vs.(25.2 ± 5.8) min,and incidences of anastomotic leakage,bile duct infection,liver abscess,blie duct stricture postoperation (1.6％ vs.9.7％) in "end-inside" anastomosis were significantly lower than those in "mucosa to mucosal" anastomosis (P ＜ 0.05).Whether the common bile duct was dilated or not,the shrinking extents of stoma in " end-inside" anastomosis were lower than those in " mucosa to mucosal" anastomosis (1.4 ± 0.4) mm vs.(3.6 ± 1.2),(2.9 ± 0.6) mm vs.(4.2 ± 1.2) mm with statistical significances (P ＜ 0.05).There was no significant differences between two procedures when common bile duct was dilated.Conclusion Compared to the mucosa to mucosal anastomosis,the end-inside anastomosis had the advantage of easy operating and low postoperative complications when the bile duct was not dilated.

Objective To investigate the expression of Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)in peripheral blood mononuclear cells(PBMC)in children with recurrent respiratory tract infection(RRTI)and its relationship with T helper cell 1(Th1)/T helper cell 2(Th2)immune response.Methods A total of 65 children diagnosed with RRTI who admitted to the hospital from December 2020 to December 2022 were enrolled in the study as the RRTI group,and 45 healthy children who underwent physical examination in the hospital during the same period were enrolled as the control group.The relative expression levels of TLR2 and TLR4 mRNA in PBMCs were detected by real-time fluorescence quantitative PCR(qPCR).The expres-sion rates of TLR2 and TLR4 protein in PBMCs were detected by flow cytometry.The levels of Th1 cytokine interferon-γ(IFN-γ),Th2 cytokine interleukin-4(IL-4)and their ratio(IFN-γ/IL-4)in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the corre-lation between TLR2,TLR4 protein expression rates and plasma IFN-γ,IL-4 levels.Results The RRTI group had significantly higher plasma level of Th2 cytokine IL-4 than the control group,significantly lower plasma level of Th1 cytokine IFN-y than the control group,and significantly lower ratio of IFN-γ/IL-4 than the con-trol group,the differences were all statistically significant(P＜0.05).The relative expression levels of TLR2 and TLR4 mRNA and protein expression rates in PBMC of children in the RRTI group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that the protein expression rates of TLR2 and TLR4 in PBMC of children with RRTI were both nega-tively correlated with both plasma IFN-γ levels and IFN-γ/IL-4(P＜0.05)and positively correlated with plasma IL-4 levels(P＜0.05).Conclusion The expression of TLR2 and TLR4 in PBMC and plasma Th1/Th2 cytokines in children with RRTI may be involved in the occurrence and development of the disease.Ex-cessive activation of TLR2 and TLR4 may weaken Th1 function and enhance Th2 function.

Objective To evaluate the clinical efficacy of en-bloc kidney transplantation from infantile organ donation after citizen's death to adult recipients. Methods Clinical data, surgical approach, use of immunosuppressive agents and follow-up of two adults undergoing kidney transplantation from infantile donor organs were retrospectively analyzed. Relevant literature review was performed. Results One male recipient was diagnosed with primary diseases of chronic renal lesions and renal failure. After kidney transplantation, the recipient obtained favorable recovery of kidney function. The grafted kidney was gradually increased in size. During the final follow-up (10 months after surgery), the serum creatinine level was measured as 84 μmol/L. The other female recipient was diagnosed with renal failure accompanied with uremia. The recipient died from heart failure complicated with severe pulmonary infection at postoperative 23 d. No vascular complications occurred in either recipient. Conclusions Kidney transplantation from infantile donor organs to adult recipients yields favorable clinical efficacy and the grafted kidney is significantly increased in size during the early stage. Precise intraoperative manipulation contributes to preventing the incidence of arterial embolism of the donor kidney and other postoperative complications.

Objective To investigate the prognosis relevant factors of laryngeal squamous cell carcinoma (LSCC).Methods From January 2013 to December 2013,the clinical data of 71 patients with LSCC who were initially treated in Zhejiang Cancer Hospital were retrospectively analyzed.Results Univariate analysis showed that there were statistically significant differences in survival rate between the group of supraglottic type and glottic type (60.0% vs.86.3% ,χ2 =6.284,P<0.05),the group of N0 and N+(41.7% vs.86.4% ,χ2 =16.803,P<0.01), the group of early and late stage(93.6% vs.50.0% ,χ2 =19.854,P<0.01).There were no statistically significant differences in survival rate between the group of age ≤50,>50-60,>60-70 and >70(88.9% vs.88.2% vs. 79.3% vs.62.5% ,χ2 =3.909,P>0.05),the group of T1+T2 and T3+T4(83.6% vs.62.5% ,χ2 =3.623,P>0.05),the group of high,medium,low differentiated and unsigned(75.0% vs.69.7% vs.83.3% vs.91.7% ,χ2 =3.780,P>0.05),the group of surgery,radiotherapy and surgery+radiotherapy (74.3% vs.90.9% vs.71.4% , χ2 =2.437,P>0.05).Multivariate analysis showed that age( P =0.003),treatment( P =0.048) had significant effect on the prognosis of patients,but tumor location(P=0.766),T stage(P=0.677),N stage(P=0.482),clinical stage(P=0.825),the degree of pathological differentiation(P=0.206) had no significant effect on the prognosis of patients.Conclusion More aggressive treatment should be supplied for patients with N+,advanced clinical stage and age whom the prognosis are usually poor. In addition, the proportion of tracheal tube extraction should be appreciated.

Objective:To explore the efficacy and safety of TiRobot combined with three-dimensional imaging in the minimally invasive surgery for pelvic fractures.Methods:A retrospective analysis was conducted of the 40 patients with pelvic fracture who had been treated by fixation with S1 and S2 sacroiliac screws at Department of Orthopaedics and Traumatology, Yangjiang People's Hospital from January 2019 to May 2021. They were divided into 2 groups according to their treatment methods. In the TiRobot group of 20 cases subjected to percutaneous sacroiliac screw fixation assisted by TiRobot combined with three-dimensional imaging, there were 13 males and 7 females with an age of (38.2 ± 8.8) years. In the manual group of 20 cases subjected to fixation with manual placement of sacroiliac screws under conventional C-arm fluoroscopy, there were 11 males and 9 females with an age of (37.3 ± 9.2) years. The 2 groups were compared in terms of fluoroscopy time for screw placement, guide needle adjustment, operation time, intraoperative blood loss, visual analogue scale (VAS) 72 hours after operation, postoperative hospital stay, time to ambulation, excellent to good rate of screw placement, complication rate, fracture union time, Majeed score at 6 months after operation, and excellent to good rate of functional evaluation.Results:There was no significant difference between the 2 groups in their preoperative general data, showing they were comparable ( P > 0.05). In the TiRobot group, fluoroscopy time for screw placement [(8.2 ± 2.9) s], guide needle adjustment [(0.4 ± 0.2) times], operation time [(67.4 ± 5.5) min], and intraoperative blood loss [(36.5 ± 8.0) mL] were significantly less than those in the manual group [(40.4 ± 4.5) s, (8.6 ± 0.7) times, (78.4 ± 7.2) min, and (41.6 ± 7.8) mL], postoperative VAS [3.0 (4.0, 5.0) points] was significantly lower than that in the manual group [4.0 (5.0, 6.0) points], the excellent to good rate of screw placement (100%, 40/40) was significantly higher than that in the manual group (85.0%, 34/40), and the complication rate (5.0%,1/20) was significantly lower than that in the manual group (35.0%, 7/20) (all P < 0.05). There was no significant difference between the 2 groups in postoperative hospital stay, time to ambulation, fracture union time, Majeed score, or excellent to good rate of functional evaluation ( P > 0.05). Conclusion:In the minimally invasive surgery for pelvic fractures, TiRobot combined with three-dimensional imaging leads to positive outcomes, because it can reduce operation time and radiation exposure, improve accuracy of screw placement, and increase safety.