Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

Objective To explore the effect of adeno-associated virus sense transfection up-regulating the expression level of the growth and differential factor 11 (GDF11) in vivo on aortic injury in type 2 diabetic mellitus rats (T2DM).Methods Nine-week-old male SD rats were randomly selected to establish a T2DM model by using high-sugar and high-fat chow plus small-dose streptozotocin (STZ) combined induction.Both normal rats and dia-betic model rats were randomly divided into five groups:blank control group (Control group) , negative virus con-trol group (NC group), GDF11 adeno-associated virus group (GDF11 group), diabetic group (DM group), and diabetic + GDF11 adeno-associated virus group (DM+GDF11 group) .After 8 weeks of feeding, the serum con-centrations of insulin (INS) , advanced glycosylation end products (AGES) , recombinant growth transforming fac-tor 11 (GDF11), total cholesterol (T-CHO), triglycerides (TG), low-density lipoproteins (LDL-C), high-densi-ty lipoproteins (HDL-C) , asymmetric dimethylarginine (ADMA) , and malondialdehyde (MDA) were assayed in the rats;periodic acid-schiff stain(PAS stain) was used to observe the sites of glycogen deposition, and hematoxy-lin-eosin staining (HE) was used to observe vascular damage.Scanning electron microscopy was used to observe the damage of vascular endothelial cells and vascular elastic fibers, and protein blotting and immunohistochemistry were used to detect the expression levels of vascular injury-related proteins.Protein blotting and immunohistochem-istry were used to detect the expression levels of vascular injury-related proteins.Results The biochemical inde-xes showed that the serum concentrations of AGES, T-CHO, TG, LDL-C and MDA were higher in the DM group than those in the Control group (P<0.05), the concentrations of INS, GDF11, HDL-C and ADMA were signifi-cantly lower than those in the Control group (P<0.05) , and the concentrations of AGES and HDL-C were not sig-nificantly lower in the DM+GDF11 group compared with the DM group (P<0.05) .HDL-C was not significantly different from the DM group, and several other data were improved (P<0.05) .Pathological staining suggested that PAS staining in the DM group suggested that glycogen particles deposited in the endothelium and subendotheli-um of the aorta, HE staining observed thickening of the aortic mesentery, endothelial cells and elastic fibers broke off in an irregular alignment, and electron microscopy observed endothelial damage in the vasculature and elastic fi-bers broke off in the DM group, and these changes attenuated in the DM+GDF11 group.Protein blotting and im-munohistochemistry indicated that the expression of endothelial cell-associated proteins decreased in the DM group (P<0.05) , and mesenchymal markers elevated in the DM group (P<0.05) , these proteins were regressed in the DM+GDF11 group, and the difference was statistically significant (P <0.05).Conclusion Increasing the expression level of GDF11 in vivo can improve aortic vascular injury caused by diabetes mellitus, which is inferred that it may be related to the inhibition of endothelial mesenchymal transition to protect the function of vascular endo-thelial cells and thus improve vascular injury.

ObjectiveTo observe the lower limb muscle activation strategy of healthy middle-aged and old women during stair ascent and descent with surface electromyography. MethodsFrom August, 2021 to February, 2022, 20 healthy middle-aged and old women were measured the surface electromyography root mean square (RMS) and integrated electromyography (iEMG) of bilateral vastus lateral, rectus femoris, vastus medialis, biceps femoris and semitendinosus during stair ascent and descent, and co-contraction ratio was calculated. ResultsDuring stair ascent, the RMS of bilateral vastus lateral, rectus femoris and vastus medialis was higher at starting stage than at following stage (|t| > 6.650, P < 0.001), while the RMS of biceps femoris and semitendinosus was lower (t > 3.559, P < 0.01); and the co-contraction ratio of hamstrings/quadriceps was lower at starting stage than at following stage (t > 8.185, P < 0.001). During stair descent, the RMS of bilateral vastus lateral, vastus medialis, biceps femoris and semitendinosus was higher at following stage than at starting stage (t > 2.345, P < 0.05), as well as the co-contraction ratio of hamstrings/quadriceps (t > 2.405, P < 0.05). ConclusionThe activities of the muscles around the knees are almost symmetrical during stair ascent and descent for healthy middle-aged and old women. The activation and co-contraction ratio of quadriceps and hamstring are various at starting/following stages.

Objective:To observe the regulatory effect of p38 mitogen-activated protein kinase (p38 MAPK) on aquaporin 4 (AQP4) in rats after hydrocephalus, and to explore its significance in hydrocephalus prevention.Methods:Fifty SD rats were randomly divided into sham-operated group ( n=10), hydrocephalus group ( n=20), and hydrocephalus+inhibitor (SB203580) group (SB group, n=20). The rat models of hydrocephalus in the latter two groups were prepared by intracerebroventricular injection of kaolin suspension; rats in the sham-operated group were injected with same amount of normal saline into the lateral ventricle. The p38 MAPK specific inhibitor SB203580 (10 mg/kg) was intraperitoneally injected into the rats of SB group on the 8 th d of modeling for 7 consecutive d; same volume of dimethylsulfoxide was given to the rats of hydrocephalus group on the 8 th d of modeling for 7 consecutive d; rats in the sham-operated group did not give any treatment. The severity of hydrocephalus in these rats was observed by MRI. The inflammatory factor tumor necrosis factor (TNF)-α level in the cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). The AQP4 and TNF-α mRNA expressions were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylated p38 MAPK and AQP4 expressions in the periventricular brain tissues were detected by Western blotting and immunohistochemistry. Results:No hydrocephalus developed in sham-operated group and hydrocephalus developed in the latter two groups. As compared with sham-operated group, hydrocephalus group and SB group had significantly increased lateral ventricle volume, significantly aggravated periventricular edema, significantly higher EVAN's index, and statistically increased brain water content ( P<0.05). Two weeks after modeling, the TNF-α expression levels in cerebrospinal fluid of sham-operated group, hydrocephalus group and SB group were (20.49±0.96), (42.04±3.17), and (28.00±3.71) pg/mL, respectively, with significant differences ( F=186.000, P<0.001); the TNF-α expression level in SB group was significantly higher than that in sham-operated group and significantly lower than that in hydrocephalus group ( P<0.05). Two weeks after modeling, the TNF-α and AQP4 mRNA expression levels in brain tissues of the three groups were significantly different ( P<0.05); the TNF-α and AQP4 mRNA expression levels in hydrocephalus group were significantly higher than those in sham-operated group and SB group ( P<0.05). Correlation analysis showed that there was a positive linear correlation between AQP4 mRNA expression and TNF-α mRNA expression in hydrocephalus group ( r=0.511, P=0.026), and there was a positive linear correlation between AQP4 protein expression and phosphorylated p38 MAPK protein expression in hydrocephalus group and SB group ( r=0.560, P=0.013; r=0.463, P=0.030). Immunohistochemical staining results showed that AQP4 expression was abundant in glial cells of the three groups; the p38 MAPK distribution was uniform and non-polar; the phosphorylated p38 MAPK protein expression in the hydrocephalus group was significantly higher than that in the sham-operated group, and that in the SB group returned to the level of the sham-operated group. Conclusion:The p38 MAPK pathway is involved in the positive regulation of AQP4 expression, which could be inhibited by SB203580.

Thirteen patients with colorectal lesions underwent laparoscopic surgery from January to December 2019. Before surgery, 5.0 ml autogenous blood was injected under colonoscopy into the inferior margin and opposite sides of the lesion for localization. The operation time，success rate，complications，location efficiency and postoperative pathology were evaluated. The autologous blood tattooing was easily applied for all patients without complication. At laparoscopic surgery，the lesions of all patients were clearly visualized except one obese patients with rectal tumors, because the tumor was located below the retroperitoneal fold. No blood diffusion and leakage，and local inflammatory responses were observed. The surgical margins of all samples were tumor negative. Preoperative tattooing with autologous blood is recommended as an easy，safe and economical procedure for colonoscopic surgery in patients with colorectal lesions.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Twelve patients with complex anal fistulas were treated in the Affiliated Hospital of Medical School of Ningbo University from June to December 2018. All the patients were successfully operated, and after the operation the wound was rinsed twice a day by buried drainage tube. Patients were followed up for 3 months, the wound was healed in 11 cases and relapsed in 1 case with a mean wound healing time of (25.2±7.0) d; the pain scores at 1 d, 3 d and 5 d after surgery were 3.21±1.27, 2.34±1.22 and 1.89±0.78, respectively. There was no significant difference in preoperative and postoperative Wexner scores, anal resting pressure, and anal maximum systolic pressure (P>0.05).This innovative technique with buried drainage tube is safe and effective, which can shorten the recovery time and reduce the recurrence rate.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Objective:To describe a new technique for chronic anal fissure surgery aimed at minimal invasion and reducing pain, and to evaluate the preliminary results concerning non-healing and intact anal function.Methods:A prospective observational study in twenty-five chronic anal fissure patients treated by Intersphincteric Lateral Internal Sphincterotomy (ILIS) technique from February to June 2018 in the Affiliated Hospital of Medical School of Ningbo University were conducted.Results:Chronic anal fissure in twenty-five patients healed primarily (96%, 24/25). There was one non-healing case. The mean healing time was(14.66 ± 5.63) d. Pain scores of 1, 3 and 5 d after surgery were (2.32 ± 0.82), (1.66 ± 0.74), (1.22 ± 0.63) scores. None had disturbance in clinical anal continence. Wexner score was 0.Conclusions:The early outcome of the ILIS technique is quite impressive. This technique is minimally invasive, with shorter healing time and less pain. It has the potential to become a viable option for chronic anal fissure surgery.

OBJECTIVE： To establish a method for simultaneous determination of nine components in Huoxiang zhengqi oral liquid， and to improve and perfect the quality standard of Huoxiang zhengqi oral liquid. METHODS： The contents of nine components in 10 batches of Huoxiang zhengqi oral liquid were determined by HPLC， such as licorice coumarin， isorlicin， liquiritinapioside， narirutin， liquiritin， saponins， hesperidin， magnolol and honokiol. The determination was performed on Kromasil Eternity XT-5-C18 column with mobile phase consisted of acetonitrile-0.05％ phosphoric acid solution （gradient elution） at the flow rate of 1 mL/min. The detection wavelength was set at 220 nm， and column temperature was 25 ℃. The sample size was 10 μL. RESULTS： The linear range of licorice coumarin， isorlicin， liquiritinapioside， narirutin， liquiritin， saponins， hesperidin， magnolol and honokiolin were 0.000 5-0.007 5， 0.000 8-0.025 0， 0.006 1-0.976 0， 0.001 6-0.250 0， 0.007 8-0.025 0， 0.000 4- 0.062 7， 0.008 6-0.276 0， 0.010 0-0.500 0， 0.010 0-0.500 0 mg/mL （r＝0.999 2-1.000 0）. The detection limits were 0.001 3， 0.000 1， 0.004 7， 0.005 0， 0.012 0， 0.001 3， 0.007 8， 0.007 7 0， 0.005 8 μg/mL， and the quantitative limits were 0.013 0， 0.000 8， 0.047 0， 0.050 0， 0.120 0， 0.013 0， 0.078 0， 0.070 0， 0.058 0 μg/mL， respectively； RSD of precision， stability and repeatability tests were less than 3.0％ （n＝6）. Average recovery rates were 98.67％， 101.85％， 98.97％， 103.05％， 100.00％， 97.78％， 97.91％， 100.13％， 101.95％； RSDs were 1.14％， 2.18％， 0.40％， 0.17％， 1.38％， 0.85％， 1.38％， 0.10％， 1.35％ （n＝6）. CONCLUSIONS： The established method is accurate and reliable， which can provide reference for the establishment of the overall quality control evaluation system and the improvement of quality standard for Huoxiang zhengqi oral liquid.