OBJECTIVE To investigate the transfer and diffusion of berberine hydrochloride(BBH), the main active component of Coptis and Phellodenticum in the system of carboxymethyl chitosan(CMCS)-sodium alginate(SA). METHODS CMCS and SA were stirred in a certain proportion, and D-gluconolactone(GDL) was added to form polyelectrolyte hydrogel. Rheometer was used to study the rheological properties of CMCS-SA hydrogel, including the elastic modulus G′ and the viscous modulus G′′. A BBH diffusion model for CMCS-SA hydrogel was designed, and the relevant rules of BBH permeation through CMCS-SA polyelectrolyte hydrogel were observed by UV-VIS. RESULTS The elastic modulus G′ of the hydrogel was measured when the ratio of CMCS to SA was 3∶1, 2∶1, 1∶1, 1∶2, and 1∶3. When the ratio of CMCS to SA was 1∶1, G′ was the highest, and the crosslinking strength of the hydrogel was the highest. The cumulative amount of BBH transfer was measured by the BBH transfer model, and the diffusion of BBH in CMCS-SA hydrogel was fitted as the skeleton dissolution by Peppas equation, indicating that BBH dissociation and the transfer efficiency increased as the amino group of CMCS decreased or the carboxyl group of SA increased. The elastic modulus G′ of CMCS-SA hydrogel increased with the increase of GDL content. The reason was that the binding force between CMCS and SA molecules gradually increased with the decrease of pH, and the crosslinking degree of the hydrogel was enhanced. When ratio of fixed CMCS to SA was 1∶1 and the GDL content was 0.15 g·mL−1, the formability of CMCS-SA hydrogel was good. In addition, when BBH was transferred in hydrogel with different concentrations of GDL, the transfer efficiency increased with the increase of GDL content. When BBH was delivered in different thickness hydrogel, the delivery efficiency of CMCS-SA hydrogel increased with the decrease of thickness. CONCLUSION The CMCS-SA hydrogel system, as a potential drug carrier for traditional Chinese medicine extracts such as BBH, is expected to serve as a gel carrier for transdermal drug delivery.

Gel materials have advantages such as comfortable touch, good air permeability, high viscoelasticity, etc., so they are widely used in modern transdermal drug delivery preparations such as patches, gel agents and film agents. With the innovative development of medical materials, many new gel materials with excellent functions have emerged, which has expanded the application scope of transdermal drug delivery preparations and optimized their properties. The classification, properties and application of gel materials in transdermal drug delivery system were reviewed, and the latest research progress was summarized, so as to provide reference for the innovative application of gel materials in transdermal drug delivery system.m.

Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.

Objective To report and analyze the clinical characteristics of kidney transplant recipients(KTRs)combined with novel coronavirus Omicron variant strain infection of novel coronavirus(SARS-CoV-2),and to investigate the possible factors affecting the serum creatinine change.Methods The patients under-going allogeneic kidney transplantation and complicating Omicron variant strain infection in this hospital from October 2022 to December 2023 were retrospectively observed.Their clinical data,basic complications and prognosis,etc.were collected and analyzed.The possible factors affecting the serum creatinine change were an-alyzed.Results Among the 114 cases of KTRs combined with Omicron variant strain infection included in this study,there were 90 cases(78.9％)in the home management group(group A),18 cases(15.8％)in the non-intensive isolation ward group(group B)and 6 cases(5.3％)in the ICU group(group C).The most common symptoms were in turn fever(90.4％),fatigue(65.8％)and cough(61.4％),the clinical manifesta-tions were mainly upper respiratory tract infection symptoms.The overall mortality rate was 2.6％(3/114),moreover the dead patients all were in the group C.The number of basic comorbidities in the group C was higher than that in the group B and group A(P＜0.05).The patients were re-divided into 33 cases(28.9％)in the creatinine increase group(group D),71 cases(62.3％)in the creatinine unchange group(group E)and 10 cases(8.8％)in the creatinine decrease group(group F).The patients in the F group were the patients with mild and moderate Omicron variant strain infection in the group A,and a larger proportions of the pa-tients in the group D and group F discontinued or reduced the calcineurin inhibitor(CNI)type drugs than in the group E.Conclusion The hazard of Omicron variant strains to KTRs has been greatly reduced compared with previous other variant strains.Realizing the immune balance between anti-infection and anti-rejection is the effective measure for preventing renal function damage in KTRs.

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Objective:To explore the association between dietary patterns and the incidence of type 2 diabetes mellitus(T2DM), so as to provide insights for the prevention and management of T2DM.Methods:Participants were recruited from the " The Tianjin Chronic Inflammation and Health Cohort Study(TCLSIH)" cohort study from 2013 to 2018, who had completed the modified semiquantitative food frequency questionnaire(FFQ) and blood glucose testing( n=26 425), free of cardiovascular disease, cancer, or diabetes at baseline. The relevant information collected includes food frequency, blood glucose concentration, and other confounding factors. In this study, the correlation between dietary patterns and T2DM was tested using Cox proportional risk regression model, and the gender stratification analysis and body mass index stratification analysis of different gender groups were carried out. All statistical analysis was performed using SAS 9.3 software. Results:The age of all participants was (41.0±11.5)years, and the cumulative incidence was 3.84% for T2DM. The cumulative incidence of T2DM in male population was 5.29%, while that in female population was 2.16%. There were significant differences in the incidence of T2DM among different genders( P <0.001). The multivariable-adjusted hazard ratios( HR) and corresponding 95% CI of T2DM across the plant-based dietary pattern score were 1.09(95% CI 0.91-1.31), 0.80(95% CI 0.66-0.97), and 0.76(95% CI 0.62-0.94; Ptrend =0.010). Moreover, no statistically significant differences were observed between animal and traditional northern Chinese diets with the incidence of T2DM. Conclusions:The plant-based dietary patterns were associated with substantially lower risk of developing T2DM, and there were no significant association between animal and traditional northern Chinese dietary patterns with T2DM. Plant-based dietary patterns characterized by a variety of fruit, leeks, onions, seaweed may be beneficial to the prevention and control of T2DM.

Cranial defect restoration is popular in forensic anthropology,craniofacial surgery,and archaeology.Virtual 3D restoration developed fast and has a broad prospect since computer assisted method applied in cranial facial defect restoration based on CT scans.In recent years,with the continuous development of computer algorithms and software,the 3D cranial facial defect restoration methods have been increasing.The purpose of this paper is to summarize the computer-aided 3D cranial facial defect restoration based on CT scans published in the past two decades and to research the current progress.

Objective:To compare the clinical efficacy between robot-assisted and free-hand percutaneous cannulated screwing (PCS) in the treatment of femoral neck fractures in the middle-aged and young patients.Methods:A retrospective study was conducted to analyze the clinical data of 53 patients with femoral neck fracture who had been treated with PCS from May 2020 to May 2022 at Department of Traumatic Surgery, Maoming Hospital Affiliated to Southern Medical University. In the robot group of 25 patients subjected to robot-assisted PCS, there were 11 males and 14 females with an age of (48.2 ± 11.9) years; in the free-hand group of 28 patients subjected to free-hand PCS, there were 13 males and 15 females with an age of (48.5 ± 9.8) years. The 2 groups were compared in terms of operation time, intraoperative bleeding, intraoperative guide drills, intraoperative fluoroscopy frequency, fracture union time, Harris hip score at the last follow-up and postoperative complications. Postoperative imaging examination was performed to evaluate distribution accuracy of the cannulated screws in the femoral neck (deviation between the screws and the femoral neck axis, parallelism between the screws and distance between the screws and the neck cortex).Results:There was no statistically significant difference between the robot and free-hand groups in the general clinical data before operation, showing comparability ( P>0.05). The robot group showed significantly shorter operation time [(32.7 ± 4.8) min], significantly less intraoperative bleeding [(14.6 ± 4.8) mL], significantly less intraoperative guide drillings [(3.5 ± 0.7) times] and significantly less intraoperative fluoroscopy frequency [(7.9 ± 1.4) times] than the free-hand group [(56.9 ± 11.3) min, (27.0 ± 7.3) mL, (9.1 ± 1.8) times and (16.3 ± 6.0) times)] (all P<0.05). Postoperative imaging showed that the deviation between the screws and the femoral neck axis was 4.4° ± 1.1° on the anteroposterior X-ray film and 3.2° ± 0.8° on the lateral X-ray film, the parallelism between the screws 4.9° ± 0.8° on the anteroposterior X-ray film and 3.0° ± 0.7° on the lateral X-ray film, and the distance between the screws and the femoral neck cortex (10.4 ± 2.7) mm in the robot group, all significantly smaller than those in the free-hand group [10.5° ± 2.8°, 4.9° ± 1.1°, 12.1° ± 4.0°, 5.1° ± 1.3°, and (15.4 ± 3.2) mm] (all P<0.05). All the 53 patients were followed up for (22.2 ± 8.5) months. All fractures got united. The fracture union time in the robot group [(20.6 ± 4.6) weeks] was insignificantly shorter than that in the free-hand group [(23.7 ± 7.7) weeks] ( P>0.05). At the last follow-up, the Harris hip score in the robot group [(88.6 ± 5.6) points] was significantly higher than that in the free-hand group [(84.8 ± 6.3) points] ( P<0.05). Follow-ups revealed 2 cases of internal fixation loosening, 1 case of screw head cutting and 1 case of femoral head necrosis in the free-hand group but none of such complications in the robot group. Conclusion:In the treatment of femoral neck fractures in the middle-aged and young patients, compared with free-hand PCS, robot-assisted PCS shows advantages of shorter intraoperative time, less bleeding, less fluoroscopic radiation, higher accuracy of screw placement, a lower incidence of postoperative complications and better functional recovery of the hip joint.

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.

Objective:To learn about the epidemiological and spatial clustering characteristics of brucellosis in Shandong Province, and to provide a reference for scientific prevention and control of brucellosis.Methods:The epidemic data of human brucellosis in Shandong Province from January 2015 to December 2020 were collected from the Infectious Disease Reporting Information Management System of China Disease Control and Prevention Information System, and the data were analyzed by descriptive epidemiology and spatial clustering analysis.Results:A total of 18 811 cases of human brucellosis were reported in Shandong Province from 2015 to 2020, and the average annual incidence rate was 3.16/100 000. Human brucellosis occurred in every month of the year, and the peak incidence was from March to August, accounting for 66.31% (12 474/18 811). The top 5 counties (districts) with average annual incidence rates were Lijin County (32.39/100 000), Kenli District (11.02/100 000), Wudi County (10.35/100 000), Zhanhua District (9.59/100 000) and Shanghe County (8.80/100 000). There were 13 436 males and 5 375 females, with a male-female sex ratio of 2.50 ∶ 1.00; the age was mainly concentrated in 30-69 years old, accounting for 83.23% (15 656/18 811); farmer was the main occupation, accounting for 85.82% (16 144/18 811). The results of global spatial autocorrelation analysis showed that the annual incidence rates of brucellosis in Shandong Province showed a spatial clustering distribution from 2015 to 2020; and the local spatial autocorrelation analysis showed that the high incidence of human brucellosis was mainly concentrated in the north of Shandong Province.Conclusions:The incidence of brucellosis in Shandong Province is mainly concentrated in spring and summer, most of them are farmers, and the high incidence areas have spatial clustering. Key prevention and control measures should be taken for high incidence seasons, high-risk population and northern high clustering areas to reduce the incidence of brucellosis.