Hepatolenticular degeneration is an autosomal recessive hereditary disease characterized by copper metabolism disorder,which affects the liver,kidneys,and brain.In traditional Chinese medicine,this disease is closely associated with dysfunction of the"liver-kidney-brain"axis.The liver,kidney,and brain form a physiological whole through the mutual transformation and distribution of essence and blood,the coordination of qi transformation,and the connection of meridians and collaterals.This article explores the pathogenesis of hepatolenticular degeneration based on the"liver-kidney-brain"axis.The deficiency of liver and kidney essence leads to the malnutrition of brain marrow,which is the fundamental cause of the disease.The internal accumulation of copper toxins generates dampness-heat and phlegm-stasis,which are the key factors causing the disease.In view of the characteristics of this disease with deficiency in nature and excess in superficiality,the principle of dynamic treating both manifestation and root cause of disease is established:treating the manifestation starts with eliminating copper and detoxifying,combined with clearing heat and dampness,and removing phlegm and stasis;treating the root cause follows the concept of the same origin of yi and gui,emphasizing the simultaneous treatment of liver and kidney to nourish the brain marrow.Throughout the treatment process,copper elimination(treating the symptoms)should be taken into account,and stratified measures should be applied based on the primary focus of the lesion:either treating the liver as the main focus and supplemented by tonifying the kidney and filling the marrow;or treating the kidney as the main focus and assisted by regulating the liver and nourishing the brain;or co-regulating the three zang-organs of liver,kidney,and brain,to achieve the therapeutic goal of eliminating pathogenic factors and restoring normal functions,and combining tonification and purgation.

Hepatolenticular degeneration is an autosomal recessive hereditary disease characterized by copper metabolism disorder,which affects the liver,kidneys,and brain.In traditional Chinese medicine,this disease is closely associated with dysfunction of the"liver-kidney-brain"axis.The liver,kidney,and brain form a physiological whole through the mutual transformation and distribution of essence and blood,the coordination of qi transformation,and the connection of meridians and collaterals.This article explores the pathogenesis of hepatolenticular degeneration based on the"liver-kidney-brain"axis.The deficiency of liver and kidney essence leads to the malnutrition of brain marrow,which is the fundamental cause of the disease.The internal accumulation of copper toxins generates dampness-heat and phlegm-stasis,which are the key factors causing the disease.In view of the characteristics of this disease with deficiency in nature and excess in superficiality,the principle of dynamic treating both manifestation and root cause of disease is established:treating the manifestation starts with eliminating copper and detoxifying,combined with clearing heat and dampness,and removing phlegm and stasis;treating the root cause follows the concept of the same origin of yi and gui,emphasizing the simultaneous treatment of liver and kidney to nourish the brain marrow.Throughout the treatment process,copper elimination(treating the symptoms)should be taken into account,and stratified measures should be applied based on the primary focus of the lesion:either treating the liver as the main focus and supplemented by tonifying the kidney and filling the marrow;or treating the kidney as the main focus and assisted by regulating the liver and nourishing the brain;or co-regulating the three zang-organs of liver,kidney,and brain,to achieve the therapeutic goal of eliminating pathogenic factors and restoring normal functions,and combining tonification and purgation.

Objective:To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL).Methods:The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years.Results:All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T 1WI and hypersignal on T 2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion:The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.

Objective:To evaluate the accuracy of ultrasound measurement of airway parameters in predicting difficult mask ventilation (DMV).Methods:Ninety-six patients, aged 18-90 yr, with body mass index of 16-39 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective endotracheal intubation under general anesthesia, were included in this study. Clinical airway evaluation was performed at 1 day before surgery, and modified Mallampati classification, thyromental distance and rating of the upper lip bite test were recorded. At 30 min before anesthesia induction, mandibular condylar motion, tongue longitudinal cross-sectional area and transverse diameter of tongue were measured by ultrasound, and the tongue volume (product of tongue longitudinal cross-sectional area and transverse diameter of tongue) was calculated. Mask ventilation was performed after induction of anesthesia, mask ventilation difficulty grade ≥Ⅲ was defined as DMV, the patients were divided into 2 groups according to whether DMV occurred: non-DMV group (NDMV group) and DMV group. Correlations between the clinical airway evaluation indexes and ultrasonic airway parameters with statistically significant differences between groups and DMV were assessed using Spearman′s rank correlation. The area under the receiver operating characteristics curve was used to evaluate the accuracy of each parameter in predicting DMV, the critical value was determined, and the accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Results:The modified Mallampati classification, rating of the upper lip bite test, ultrasonic tongue longitudinal cross-sectional area, transverse diameter of tongue and tongue volume were positively correlated with DMV, and thyromental distance and mandibular condylar motion were negatively correlated with DMV ( P<0.05). The area under the receiver operating characteristics curve of mandibular condylar motion and tongue volume in predicting DMV were 0.898 and 0.862, respectively, the cut-off values were 1.19 cm and 99.94 cm 3, respectively, and the sensitivity and specificity were all over 70% and 90%, respectively, the positive predictive values were 92.31% and 88.46%, respectively. Conclusions:Ultrasonic measurements of mandibular condylar motion and tongue volume can accurately predict DMV.

Three-dimensional (3D) cell culture model is a system that co-culture carriers with 3D structural materials and different types of cells in vitro to simulate the microenvironment in vivo. This novel cell culture model has been proved to be close to the natural system in vivo. In the process of cell attachment, migration, mitosis and apoptosis, it could produce biological reactions different from that of monolayer cell culture. Therefore, it can be used as an ideal model to evaluate the dynamic pharmacological effects of active substances and the metastasis process of cancer cells. This paper compared and analyzed the different characteristics of cell growth and development under two-dimensional (2D) and 3D model culture and introduced the establishment method of 3D cell model. The application progress of 3D cell culture technology in tumor model and intestinal absorption model was summarized. Finally, the application prospect of 3D cell model in the evaluation and screening of active substance was revealed. This review is expected to provide reference for the development and application of new 3D cell culture models.
Cell Culture Techniques, Three Dimensional ; Cell Culture Techniques ; Apoptosis ; Cell Proliferation ; Technology

Tumor has become the major reasons cause of death,and its vaccine has become the effective tracts of treatment and prevention by enhancing the immune response of patients.However,most vaccines which are recombination subunit protein antigens are poorly immunogenic and difficult to induce a robust immune response in patients with compromised immune systems,resulting in poor marketing approval.The core component of the vaccine adjuvant can greatly enhance the strength,speed and duration of the immune response,thus becoming the key to the development of an ideal tumor vaccine.Most tumor vaccines are combined with tradition adjuvant such as aluminum,MF59 and AS adjuvant,but their products and patents are monopolized by large foreign companies.We found that natural adjuvants have many unique advantages,such as good biocompatibility and biodegradability,promoting the maturation of dendritic cell and the secretion of immune cytokines,significantly enhancing the tumor vaccine immune response,etc.In this paper,the application and future development of natural polysaccharides,saponins,flavonoid and plant virus-like particles in cancer vaccines were reviewed,which may lay a solid foundation for the development of the original and innovative adjuvants with domestic independent intellectual property rights.

Objective:To determine the median effective dose (ED 50) of 0.5% ropivacaine based on femoral nerve cross-sectional area for ultrasound-guided femoral nerve block. Methods:Patients of both sexes, aged 18-64 yr, of American Society of Anesthesiologists physical status I or Ⅱ, with body mass index of 20-30 kg/m 2, scheduled for elective open reduction and internal fixation for patella fracture or removal of patella fracture by internal fixation, were enrolled in this study.Ultrasonic localization of femoral nerve was performed for measurement of the femoral nerve cross-sectional area, and 0.5% ropivacaine was injected based on the area.ED 50 was determined by Dixon′s up-and-down sequential method.The initial dose was 0.22 ml/mm 2, and the difference between the two successive doses was 0.02 ml/mm 2.The effective block was defined as complete loss of pain sensation in the areas of anterior skin of knee joint, skin on the inner side of the calf and dorsal medial skin of the foot and the degree of motor block was in stages 1-3 assessed using Brunnstrom motor function within 30 min after nerve block.Nerve block was considered ineffective if pain occurred in any nerve distribution area mentioned above.The study was terminated if 7 effective and ineffective alternating waves occurred.ED 50 and 95% confidence interval (CI) were calculated using Probit analysis. Results:Twenty-seven patients were enrolled in the study with the femoral nerve cross-sectional area (75±5) mm 2.ED 50 (95%CI) of 0.5% ropivacaine for ultrasound-guided femoral nerve block was 0.106 (0.069-0.125) ml/mm 2. Conclusion:ED 50 of 0.5% ropivacaine based on femoral nerve cross-sectional area for ultrasound-guided femoral nerve block is 0.106 ml/mm 2.

Objective:To determine the median effective dose (ED 50) of 0.5% ropivacaine when combined with dexmedetomidine based on femoral nerve cross-sectional area for ultrasound-guided femoral nerve block. Methods:American Society of Anesthesiologists physical statusⅠor Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 20-30 kg/m 2, scheduled for elective open reduction and internal fixation for patella fracture or removal of patella fracture by internal fixation, were randomly divided into dexmedetomidine and ropivacaine group (group DR) and ropivacaine group (group R). In group DR, 0.5% ropivacaine and 0.5 μg/kg dexmedetomidine were injected.In group R, 0.5% ropivacaine was injected.Ultrasonic localization of femoral nerve was performed for measurement of the femoral nerve cross-sectional area, and 0.5% ropivacaine was injected based on the area.ED 50 was determined by Dixon′ s up-and-down sequential method.The initial dose was 0.22 ml/mm 2, and the difference between the two successive doses was 0.02 ml/mm 2.The effective block was defined as complete loss of pain sensation in the areas of anterior skin of knee joint, skin on the inner side of the calf and dorsal medial skin of the foot and the degree of motor block was in stages 1-3 assessed using Brunnstrom motor function within 30 min after nerve block.Nerve block was considered ineffective if pain occurred in any nerve distribution area mentioned above.The study was terminated if 7 effective and ineffective alternating waves occurred.ED 50 and 95% confidence interval (CI) were calculated using Probit analysis. Results:In group R, 27 patients were enrolled in the study, and ED 50 (95%CI) of 0.5% ropivacaine for ultrasound-guided femoral nerve block was 0.106 (0.069-0.125) ml/mm 2.In group DR, 23 patients were enrolled in the study, and ED 50 (95% CI) of 0.5% ropivacaine for ultrasound-guided femoral nerve block was 0.038 (0.011-0.059) ml/mm 2.Compared with group R, ED 50 of 0.5% ropivacaine for femoral nerve block was significantly decreased in group R. Conclusion:When combined with dexmedetomidine 0.5 μg/kg, ED 50 of 0.5% ropivacaine based on femoral nerve cross-sectional area for ultrasound-guided femoral nerve block is 0.038 ml/mm 2.

Objective To evaluate the effect of propofol on high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway during hepatic ischemia-reperfusion (I/R) injury in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 3 months,weighing 250 -300 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),hepatic I/R group (group I/R) and propofol group (group P).Hepatic I/R injury was induced by occluding the portal vein and hepatic artery supplying the left and middle lobes of the liver for 1 h followed by 6-h reperfusion in anesthetized rats.Propofol was infused via the tail vein at a rate of 12 mg ·kg-1 · h-1 starting from 20 min before ischemia until 6 h of reperfusion in group P.The rats were sacrificed at 6 h of reperfusion,and the left lobe of the liver was removed for microscopic examination of the pathological changes which were scored and for determination of the expression of HMGB1,TLR4,tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-6) in liver tissues (by Western blot).Results Compared with group S,pathological scores of liver tissues were significantly increased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was up-regulated in I/R and P groups (P＜0.05).Compared with group I/R,pathological scores of liver tissues were significantly decreased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was down-regulated in group P (P＜ 0.05).Conclusion The mechanism by which propofol reduces liver I/R injury is associated with blocking HMGB-1/TLR4 signaling pathway and inhibiting inflammatory responses in rats.

Objective To investigate the distribution and drug resistance of carbapenem-resistant Enterobacteriaceae ( CRE) isolated from children in China. Methods CRE strains were collected in 10 ter-tiary children's hospitals of China from January 1, 2016 to December 31, 2017. Antimicrobial susceptibility of the clinical strains was detected with disk diffusion method ( KB method) and automated method. The re-sults were analyzed according to the Clinical and Laboratory Standards Institute ( CLSI) Standards published in 2017. WHONET 5. 6 software was used to retrospectively analyze the distribution characteristics and drug resistance of these strains. Results A total of 3065 CRE clinical strains were isolated from children with an overall prevalence of 7. 7％ and among them, 13. 5％ were isolated in neonatal group and 5. 8％ in non-neo-natal group. The detection rate of CRE in 2017 was higher than that in 2016 (9. 7％ vs 5. 7％). Among the 3065 CRE strains, there were 1912 strains of Klebsiella pneumoniae (62. 0％), 667 strains of Escherichia coli (22. 0％), 206 strains of Enterobacter cloacae (7. 0％), 56 strains of Klebsiella aerogenes (1. 8％) and 47 strains of Serratia marcescens (1. 5％). Most of the strains were isolate in neonatology departments including neonatal intensive care units (NICU) and intensive care units (ICU), accounting for 44. 8％ and 19. 7％, respectively. Respiratory tract (61. 8％), urine (19. 4％) and blood (5. 7％) specimens were the main sources of CRE isolates. Results of antimicrobial susceptibility test showed that the CRE strains were highly resistant to carbapenem antibiotics such as imipenem, meropenem and ertapenem, as well as penicillins and most cephalosporins (79. 6％-100％), especially those isolated in the neonatal group (P<0. 05). Children had relatively low resistance rates to aminoglycosides such as amikacin (19. 7％) and fos-fomycin (11. 9％), fluoroquinolones such as levofloxacin (37. 7％) and ciprofloxacin (43. 3％), and tige-cycline (3. 8％). Currently, no polymyxin B-resistant strains were isolated. Conclusions The prevalence of common CRE strains in children in 2017 was higher than that in 2016, especially in newborns. Drug re-sistance in CRE strains isolated from neonates to common antibiotics was more severe, suggesting that great attention should be paid to it and timely measures should also be taken.