Research progress of needle-free injection technology / 药学学报

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway / 中草药·英文版

OBJECTIVE@#Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.@*METHODS@#The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot.@*RESULTS@#Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers.@*CONCLUSION@#Our data supported that different CX extracts, especially CXAL and CXPHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

Navigation-assisted valgus stress method can avoid over correction of high tibial osteotomy / 中华骨科杂志

Objective:To explore the role of navigation-assisted valgus stress method in avoiding excessive correction of lower limb mechanical axis after high tibial osteotomy (HTO).Methods:A retrospective study was carried out on osteoarthritis (OA) patients who were treated with HTO for medial compartment pain of knee from January 2020 to March 2022 in the Department of Joint Surgery, Shanghai Changhai Hospital, the First Affiliated Hospital of Naval Medical University. According to the different ways of confirming alignment during operation, they were divided into computer navigation assisted valgus stress HTO group (referred to as navigation group) and traditional rod fluoroscopy HTO group (referred to as traditional group). There were 28 patients in the navigation group, 10 males and 18 females, with age of 54.4±9.1 years (range, 41-73 years) and body mass index of 26.1±3.3 kg/m 2 (range, 19.8-35.2 kg/m 2); There were 30 patients in the traditional group, 13 males and 17 females, aged 56.9±8.5 years (range, 40-70 years), with a body mass index of 25.7±4.0 kg/m 2 (range, 19.2-32.9 kg/m 2). Measuring the mechanical femoral tibial angle (mFTA), joint line convergence angle (JLCA), medial proximal tibial angle (MPTA), Lysholm score and Hospital for Special Surgery (HSS) score before operation and at the last follow-up of the two groups, and conduct statistical analysis. Results:Both groups were followed up. The follow-up time of navigation group and traditional group was 21.3±8.7 months and 22.5±7.6 months, respectively, with no significant difference ( t=0.53, P=0.596). There were significant differences between the two groups in the amount of mechanical axis correction (ΔmFTA) and the amount of bone correction (ΔMPTA) ( t=2.09, P=0.041; t=2.58, P=0.012), while there was no significant difference in ΔJLCA ( t=0.32, P=0.753). In the navigation group, there were 9 cases (32%) of undercorrection, 17 cases (61%) with acceptable alignment, and 2 cases (7%) with over correction, while in the traditional group, there were 5 cases (17%) with under correction, 13 cases (43%) with acceptable alignment, and 12 cases (40%) with over correction. There was significant difference in the distribution rate of alignment between the two groups ( P=0.012), and the rate of overcorrection in the navigation group was significantly lower than that in the control group (7% vs. 40%, P=0.005). The intra group correlation coefficient between the navigation correction mechanical axis and ΔmFTA was 0.787. There was no significant difference in Lysholm score and HSS score between the two groups before and after surgery (all P>0.05), and they were significantly improved after operation (all P<0.05). Conclusion:Navigation-assisted valgus stress method HTO is reliable, which can accurately achieve the target alignment, reduce the incidence of over correction, and obtain good clinical results.

Exposure to specific far-infrared ray based on gra-phene film promotes exercise capacity and glucose metabolism via AMPK / 中国药理学与毒理学杂志

OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.

Guiding role of three-dimensional simulation modeling technology in laparoscopic-assisted radical resection of rectal cancer / 国际外科学杂志

Objective:Three-dimensional simulation modeling technology was used to conduct three-dimensional reconstruction, classification and measurement for the anatomic structures of colorectal canal, tumor and key blood vessels in patients with rectal cancer before operation. And the accuracy of the data and information obtained for the prediction of anastomotic tension, important types of vascular variant, positioning of anatomical landmarks, etc. in laparoscopic-assisted radical resection of rectal cancer, and the guiding effect of operation was evaluated.Methods:The clinical data of 50 patients with laparoscopic-assisted radical resection of rectal cancer treated in the General Surgery Department, Beijing Ditan Hospital Capital Medical University from January 2019 to February 2021 were analyzed retrospectively, including 31 males and 19 females, aged from 42 to 83 years old, with an average age of (62.72 ±15.21) years. The patients were divided into two groups according to whether the patients underwent three-dimensional simulation reconstruction before operation. The patients who underwent abdomen pelvic enhancement CT and further three-dimensional reconstruction before surgery were taken as reconstruction group ( n=24), and the patients who were only routinely performed abdomen pelvic enhancement CT before operation were taken as control group ( n=26). For the patients in the reconstruction group, the CT images were modeled by Mimics software before operation, and the key data such as the length of colorectal and tumor, the correlation length of rigid structure of pelvic wall, the length of inferior mesenteric artery (IMA) from the bifurcation point of left and right arteria iliaca communis, the type and proportion of IMA variation, the length of left colonic artery (LCA) from the beginning of IMA and the distance between LCA and IMV were measured, and the consistency correlation coefficient (CCC) was analyzed with the actual data obtained during operation. And then the accuracy of three-dimensional simulation modeling technology for surgical guidance was evaluated. MedCalc 19.0 software was used for statistical analysis. Results:In the reconstruction group, regarding the data of each dimension of the model (intestinal tract, pelvic cavity, blood vessels) and the corresponding structural measurements during the operation, the consistent correlation coefficient (CCC) evaluation was more than 0.9. One case was predicted to have free splenic flexure of colon and one case actually had free splenic flexure of colon. The prediction accuracy was 100%. The IMA variants in the reconstruction group were divided into 4 types, all of which were verified by operation. Compared with the control group, the operation time ( P=0.011) and the location time (IMA, P=0.043; LCA, P=0.007; IMV, P=0.034) of each vessel in the reconstruction group were shorter, and the amount of intraoperative blood loss was less ( P=0.017). Conclusion:The application of three-dimensional simulation modeling technology before operation is helpful for the operator to accurately predict the intraoperative anastomotic tension, the type of IMA variation and the related diameter length, based on which the accurate operation plan can be made to guide the operation.

Downward referral willingness of rehabilitation patients in an urban medical group and its influencing factors / 中国康复理论与实践

ObjectiveTo investigate the willingness of rehabilitation patients within an urban medical group to accept downward referrals and analyze the influencing factors. MethodsFrom June to October, 2023, a survey was conducted using a simple random sampling method among neurological and orthopedic rehabilitation patients in hospitals within a specific urban medical group. The 2013 version of the Andersen Model was employed to construct a theoretical framework for the willingness of rehabilitation patients to accept downward referrals and influencing factors. Within this framework, a questionnaire was designed using a 5-point Likert scale, comprising three sections including personal characteristics, environmental features and healthcare service utilization choices, totaling 23 questions. A preliminary survey was conducted, and the questionnaire had underwent reliability and validity testing. ResultsA total of 350 questionnaires were collected, with 314 valid questionnaires. The willingness of rehabilitation patients to accept downward referrals was found to be associated with age, rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals, awareness of and perceptions regarding bidirectional referral policies, and understanding and opinions about the urban medical group (χ2 > 7.755, P < 0.05). The primary influencing factors were rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies (P < 0.05). ConclusionRehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies are the primary factors that influenced the willingness of rehabilitation patients to accept downward referrals. We should formulate targeted and focused improvement measures based on the specific circumstances and key influencing factors of rehabilitation patients within the urban medical group regarding their willingness to accept downward referrals. Continuously enhancing the proportion of patients willingness to accept downward referrals is essential for the effective implementation of bidirectional referral for rehabilitation patients.

Modulation of type I interferon signaling by natural products in the treatment of immune-related diseases / 中国天然药物

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.

Visual Analysis of Knowledge Map of Constipation Treated by TCM Based on CiteSpace / 中国实验方剂学杂志

ObjectiveTo understand the current situation and hot spots of research on the treatment of constipation by traditional Chinese medicine （TCM） in China and foreign countries， and provide references and directions for future research. MethodIn this study， the data analysis software CiteSpace 5.8.R3C was used to conduct bibliometrics analysis of the relevant papers on the treatment of constipation by TCM from January 1， 2000 to December 31， 2021 in China National Knowledge Infrastructure （CNKI） and Web of Science core database. The visual display was carried out. ResultAfter retrieval， 2 133 papers were included in CNKI database and 224 papers were included in Web of Science core database. The statistical analysis showed that the overall annual publication volume in China and foreign countries was on the rise， but the publication volume in China had been declining for the past two consecutive years. The author co-occurrence analysis showed that the authors with the largest number of publications in China and foreign countries were LIU Chunqiang and CHUNGWAH CHENG， respectively. The institution co-occurrence analysis showed that the institutions with the largest number of publications in China and foreign countries were the Anorectal Department of Longhua Hospital Affiliated to Shanghai University of TCM and Beijing University of Chinese Medicine， respectively. The keyword analysis showed that research in this field in China and foreign countries mainly focused on TCM therapy， clinical research， etiology and pathogenesis， etc. ConclusionThe research on the treatment of constipation by TCM is mainly concentrated in China， but there is no closely-related scientific research team. The research in this field in China and foreign countries is still developing. With the continuous deepening of research， all research institutions should pay attention to interdisciplinary intersection， highlight technological innovation， and strive to achieve greater breakthroughs in this field.

Therapeutic Effect and Mechanism of Yiqi Huoxue Tongbian Prescription on Slow Transit Constipation in Rats / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.

Efficacy of systematic versus lobe-specific lymph node dissection in the treatment of clinicalⅠA stage lung adenocarcinoma: A propensity score matching study in a single center / 中国胸心血管外科临床杂志

@#Objective     To analyze the effects of systematic lymph node dissection (SLND) and lobe-specific lymph node dissection (L-SND) on perioperative and long-term outcomes of patients with clinicalⅠA (cⅠA) stage lung adenocarcinoma. Methods     A retrospective analysis was done on the patients with cⅠA stage lung adenocarcinoma who received thoracoscopic radical resection admitted to the Affiliated Hospital of Qingdao University from January 2013 to August 2016. Propensity score matching was conducted to eliminate the biases. The recurrence-free survival was compared between the two groups after matching. Perioperative parameters and postoperative complications were also analyzed. Results     A total of 725 patients were enrolled, including 252 males and 473 females, with a median age of 62.0 (31.0-69.0) years. There were 228 patients in the L-SND group and 497 patients in the SLND group. After matching, there were 211 patients in each group and no statistical difference in the incidence of postoperative complications (10.9% vs. 13.7%, P=0.374), identification of metastatic positive lymph nodes (12.3% vs. 9.0%, P=0.270), or recurrence-free survival (P=0.492) were found between two groups, whereas the operation time (163.9±39.4 min vs. 135.4±32.4 min, P<0.001), intraoperative blood loss [100.0 (20.0-800.0) mL vs. 100.0 (10.0-400.0) mL, P<0.001], intubation time [4.0 (1.0-18.0) d vs. 4.0 (1.0-9.0) d, P<0.001] and hospital stay (12.3±3.3 d vs. 10.8±2.4 d, P=0.003) in the SLND group were found to be significantly higher or longer than those in the L-SND group. Conclusion     L-SND has a similar efficiency to SLND in terms of postoperative complications, pathological lymph node metastasis, and recurrence-free survival, as well as significant advantages in reducing intraoperative blood loss, and shortening operation time, intubation time and length of hospital stay. Therefore, L-SND can be recommended to replace SLND as a method for lymph node resection in patients with cⅠA stage lung adenocarcinoma.

Short-term effectiveness of transverse antecubital incision for failed closed reduction of Gartland type Ⅲ supracondylar humerus fractures in children / 中国修复重建外科杂志

OBJECTIVE@#To investigate the short-term effectiveness of transverse antecubital incision in the treatment of failed closed reduction of Gartland type Ⅲ supracondylar humeral fractures (SHFs) in children.@*METHODS@#Between July 2020 and April 2022, 20 children with Gartland type Ⅲ SHFs who failed in closed reduction were treated with internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision. There were 9 boys and 11 girls with an average age of 3.1 years (range, 1.1-6.0 years). The causes of injuries were fall in 12 cases and fall from height in 8 cases. The time from admission to operation ranged from 7 to 18 hours, with an average of 12.4 hours. The healing of the incision and the occurrence of complications such as nerve injury and cubitus varus were observed after operation; the elbow flexion and extension range of motion after removing the gypsum, after removing the Kirschner wire, and at last follow-up were recorded and compared, as well as the elbow flexion and extension and forearm rotation range of motion at last follow-up between healthy and affected sides; the Baumann angle was measured on the X-ray film, and the fracture healing was observed. At last follow-up, the effectiveness was evaluated according to the Flynn elbow function evaluation criteria.@*RESULTS@#All incisions healed by first intention, and there was no skin necrosis, scar contracture, ulnar nerve injury, and cubitus varus. Postoperative pain occurred in the radial-dorsal thumb in 2 cases. The gypsum was removed and elbow flexion and extension exercises were started at 2-4 weeks (mean, 2.7 weeks) after operation, and the Kirschner wire was removed at 4-5 weeks (mean, 4.3 weeks). All the 20 patients were followed up 6-16 months, with an average of 12.4 months. The fracture healing time was 4-5 weeks, with an average of 4.5 weeks, and there was no complication such as delayed healing and myositis ossificans. The flexion and extension range of motion of the elbow joint gradually improved after operation, and there were significant differences between the time after removing the gypsum, after removing the Kirschner wire, and at last follow-up ( P<0.017). There was no significant difference in the flexion and extension of the elbow joint and the forearm rotation range of motion between the healthy and affected sides at last follow-up ( P>0.05). There was no significant difference in Baumann angle between the time of immediate after operation, after removing the Kirschner wire, and at last follow-up ( P>0.05). According to Flynn elbow function evaluation standard, 16 cases were excellent and 4 cases were good, the excellent and good rate was 100%.@*CONCLUSION@#The treatment of Gartland type Ⅲ SHFs in children with failed closed reduction by internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision has the advantages of complete soft tissue hinge behind the fracture for easy reduction and wire fixation, small incision, less complications, fast fracture healing, early functional recovery, reliable reduction and fixation, and can obtain satisfactory results.

Role of karyotyping combined with chromosomal microarray analysis in prenatal diagnosis of balanced translocation or inversion carriers / 中华围产医学杂志

Objective:To explore the value of karyotyping and chromosomal microarray analysis (CMA) in the prenatal diagnosis of balanced translocation/inversion carriers.Methods:This was a retrospective study involving 117 balanced translocation/inversion carrier couples. Among them, 90 women had a history of spontaneous abortion(≥2 times), stillbirth, fetal multiple malformations, or giving birth to children with chromosome abnormality disease and the peripheral blood karyotyping and fluorescence in situ hybridization testing confirmed that one partner was balanced translocation/inversion carrier. The present pregnancies of these cases were spontaneous and lasted until 18-25 weeks. The other 27 cases were confirmed by chromosome examination at the present pregnancy after the indication of fetal structural abnormalities by fetal karyotyping due to advanced maternal age and abnormal ultrasound and prenatal screening results. The results of karyotyping and CMA by amniocentesis during 18 to 25 gestational weeks were all summarized and described. Results:The successful rate of both methods was 100.0% (117/117). Unbalanced and balanced translocation/inversion were detected in seven (6.0%) and 39 (33.3%) fetuses by karyotyping, respectively. CMA revealed 14 fetuses with pathogenic copy number variation (CNV) and one with variants of uncertain significance(VUS), with an anomaly detection rate of 12.8% (15/117). Among the 15 cases with CNV, 13 were related to the parental translocation/inversion, one with de novo mutation (22q11.2 microdeletion syndrome), and one Duchenne muscular dystrophy mutation carrier. Based on the results of karyotype and CMA, there were 12 fetuses with unbalanced chromosomal fragments (10.3%), 37 fetuses with balanced translocation/inversion (31.6%), and 68 fetuses with normal chromosomes (58.1%). Conclusions:The combination of karyotyping and CMA can provide more accurate prenatal genetic diagnosis when one of a couple carries balanced chromosomal translocations/inversion.

Resistance of C57BL/6 Mice to Different Artemisinin-sensitive Strains of PbK173 / 中国实验方剂学杂志

ObjectiveThe tolerance of C57BL/6 mice to artemisinin-sensitive and -resistant strains of Plasmodium berghei （Pb） K173 and the differences in blood parameters， spleen coefficient and spleen structure during infection were compared to explore whether the artemisinin resistance of Pb would aggravate malaria infection. MethodPbK173 artemisinin-sensitive and -resistant strains were tested in parallel. C57BL/6 mice were randomly divided into 1 control group， 4 artemisinin-sensitive strain groups and 4 artemisinin-resistant strain groups by body weight. Each infection group was simultaneously inoculated （ip） with 1×107 infected red blood cells （iRBCs） of sensitive/resistant strain. For the mice in the survival test group， the body weight was recorded every day post infection， and the tail vein blood smear was collected to calculate the Pb infection rate. In the other infection groups， peripheral blood and spleen were collected on 2， 5 and 9 d after infection. Peripheral blood parameters， spleen coefficient， pathological section of spleen and spleen cells were detected in each group. ResultOn 1-3 d after infection， the infection rate of the resistant strain （0.4±0.0， 0.8±0.1， 1.9±0.4）% was always higher than that of the sensitive strain （0.2±0.1， 0.4±0.1， 1.1±0.3）% （P<0.01）. From the 4th d of infection， the infection rate of the two groups gradually approached. The survival period of the sensitive strain group （20.5±1.2） d was shorter than that of the resistant strain group （23.3±1.4） d （P<0.01）. On the 9th d， the white blood cell count of the sensitive strain group （16.2±1.1）×109 cells/L was higher than that of the resistant strain group （10.6±1.8）×109 cells/L （P<0.01）. Flow cytometry analysis of spleen cells showed that the sensitive strain group （3.6±0.4） demonstrated a higher CD4+/CD8+ value than the resistant strain group （2.3±0.2） on the 9th d （P<0.01）. The spleen of C57BL/6 infected mice was gradually enlarged during infection， and on the 9th d， the resistant strain group （3.1±0.1）% showed a higher spleen coefficient than the sensitive strain group （2.7±0.2）% （P<0.01）. In the early stage of C57BL/6 infected mice， the red pulp of spleen was hyperemic and swollen. On the 9th d， the marginal area of the spleen disappeared and the structure of the red and white pulp was destroyed. ConclusionWithout drug treatment， the protective immune responses of peripheral blood and spleen of C57BL/6 mice were more sensitive to PbK173 artemisinin-sensitive strain. The artemisinin-resistant strain of PbK173 bred with mouse-to-mouse blood transmission and increased artemisinin dose exhibited shortened growth period and reduced toxicity.

Research advances in intestinal flora and the development and prognosis of chronic hepatitis B / 临床肝胆病杂志

Intestinal flora is closely associated with chronic hepatitis B (CHB). Recent studies have shown that the imbalance of intestinal flora is associated with the development, progression, and prognosis of CHB, and the environment of intestinal flora may also change with disease progression, suggesting that intestinal flora and CHB interact with each other. This article reviews the influence of intestinal flora on the progression of CHB and related liver diseases and the role of intestinal flora regulation in the diagnosis and treatment of CHB and related liver diseases, in order to provide new ideas for the clinical treatment of CHB.

Long-term trajectories of lung function and risk factors in children with bronchial asthma / 中华实用儿科临床杂志

Objective:To establish the long-term trajectories of lung function in children with bronchial asthma (asthma) and explore the risk factors of persistent pulmonary dysfunction.Methods:A retrospective cohort study was conducted.Children with asthma aged above 14 years who had been followed up regularly and completed pulmonary function testing in Children′s Hospital of Capital Institute of Pediatrics were enrolled in the study from January to December 2019.Their lung function data and clinical information were collected.The latent class growth model (LCGM) was used to fit the change of lung function in children with asthma, and different trajectory groups were established.Comparison between groups was performed by t-test, ANOVA or Chi- square test.The risk factors for the lung function trajectory were analyzed by the multivariate Logistic regression method. Results:A total of 173 children with asthma, aged from 6 to 17, were enrolled, and 1 160 lung function tests were completed.Four forced expiratory volume in the first second/forced vital capacity (FEV 1/FVC) latent class trajectory groups were established, including persistent high level [27 cases (15.6%)], above average level [66 cases (38.1%)], below average level [66 cases (38.1%)], and persistent low level [14 cases (8.1%)]. In all the 4 different trajectory groups, the FEV 1/FVC values were significantly different among patients of different ages (all P<0.05). The FEV 1/FVC values of patients at all ages in the persistent high level group were above 90%.The FEV 1/FVC values of patients in other 3 level groups decreased as a whole as the age increased.FEV 1/FVC of patients in the persistent low level group decreased to below 80% when they entered the school age period and approached 70% in adolescence.The trajectory and fluctuation of maximal midexpiratory flow (MMEF), which represents the small airway function, were similar to those of FEV 1/FVC.Risk factor analysis showed that the risk of lung function decreasing below the average level in children with typical asthma was 11.940 times higher than that in children with cough variant asthma ( P=0.008). The risk of lung function deteriorating to below the average level in children with multiple allergen sensitivities was 7.462 times higher than that in children with single allergen sensitivity ( P=0.015). Children taking drugs irregularly were 6.337 times more likely to suffer persistent low lung function than children taking drugs regularly ( P=0.035). Boys were 6.186 times more likely to suffer a lung function reduction to below the average level than girls ( P=0.002). Conclusions:Four long-term trajectories of lung function in asthmatic children aged 6 to 17 years can be established: persistent high level, above average level, below average level and persistent low level.The long-term lung function of nearly a half of the asthmatic children is below the average level.Many children develop persistent airflow limitation in adolescence, and few at school age.Typical asthma, multiple allergen sensitivities, irregular medication and boy were the risk factors of long-term lung function reduction.

Structural Design and Finite Element Analysis of New Type Posterior Integral Glaucoma Valve / 中国医疗器械杂志

The treatment of refractory Glaucoma is a difficult problem in clinical ophthalmology. For refractory glaucoma patients with hyphema, shallow anterior chamber, anterior conglutination of peripheral chamber angle, corneal endothelium dystrophy or decompensated, at present, there is no effective treatment. In order to solve this problem, a new type posterior integral glaucoma valve with IOP control device was designed using medical titanium alloy, and the valve model was established by Abaqus software, and the stiffness and preload of the valve were analyzed by finite element method. The results showed that the opening and closing of the valve were controlled automatically by the pressure difference between the front and back of the valve, and the opening and flow rate of the valve increase dynamically with the increase of intraocular pressure, and finally reached the set ideal IOP value of steady state.

Comparison of short-term efficacy of VATS subxiphoid thymic tumor resection and intercostal thymic tumor resection / 西安交通大学学报(医学版)

【Objective】 To compare and analyze clinical efficacy and safety of subxiphoid vs. intercostal video-assisted thoracoscopic surgery (VATS) thymic tumor resection. 【Methods】 We selected 124 patients from January 2015 to March 2019, who received VATS thymic tumor resection in the Thoracic Department of The First Affiliated Hospital of Xi'an Jiaotong University. We divided them into the subxiphoid VATS group with 47 cases and intercostal VATS group with 77 cases to analyze clinical characteristics, postoperation outcomes, complications, pain score, and short-term quality of life. 【Results】 There were no significant differences in operation time, blood loss, the rate of postoperative pneumonia, arrhythmia, phrenic nerve paralysis or myasthenia crisis between the two groups (P>0.05). Average hospital stay: It was shorter in subxiphoid VATS group than intercostal VATS group (P<0.05). Pain score: It was lower the first day and the third day after operation in subxiphoid VATS group than in intercostal VATS group (P<0.05). SF-36 health scale score: 3-month and 12-month postoperation score was higher in subxiphoid VATS group than in intercostal VATS group (P<0.05). 【Conclusion】 Subxiphoid VATS thymic tumor resection is safe and feasible; compared with intercostal approach, it can significantly reduce wound pain and improve short-term quality of life.

High Expression of GADD45B Induced by Acid and Bile Acid is A Potential Prognostic Marker for Barrett's Esophagus-associated Adenocarcinoma / 胃肠病学

Background: Esophageal mucosal injury induced by gastroesophageal reflux is a key link to the development of Barrett's esophagus-associated adenocarcinoma. However, the molecular mechanism is still not elucidated. Aims: To investigate the role of differentially expressed genes (DEGs) after stimulating esophageal cells with acid and bile acid in the development of esophageal adenocarcinoma (EAC). Methods: The DEGs were obtained through bioinformatics methods after stimulating esophageal cells with low pH and deoxycholic acid, and GO, KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was performed to screen the hub genes, and their relationships with prognosis and tumor stage of EAC patients were analyzed. The role of co-expressed genes of GADD45B in EAC was also analyzed. Results: Thirty-one overlapping DEGs were obtained after stimulating esophageal cells with low pH and deoxycholic acid, which mainly enriched in the cytokine-cytokine receptor interaction, transcription factors activity, and regulation of cell proliferation and apoptotic process. High expression of GADD45B was correlated with the survival prognosis and tumor stage of EAC patients. GADD45B and its co-expressed genes were involved in the production of tumor necrosis factor. Conclusions: The high expression of GADD45B induced by acid and bile acid is correlated with the prognosis and tumor stage of EAC patients, and is a potential diagnosis and treatment target for Barrett's esophagus-associated adenocarcinoma.

Clinical characteristics and outcome of COVID-19 in elderly patients / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical characteristics， treatment and outcome of elderly patients with COVID-19. 【Methods】 We made a retrospective analysis of the clinical data of elderly patients with COVID-19 admitted by the National Anti-epidemic Medical Team of The First Affiliated Hospital of Xi’an Jiaotong University in Department of the seventh ward of Renmin Hospital of Wuhan University between February 9 and March 15， 2020. We fully extracted the patients’ demographics， epidemiological characteristics， clinical manifestations， laboratory examination， imaging performance， treatment and outcomes. 【Results】 In this study we included a total of 30 patients（18 males and 12 females）， with an average age of（71.1±14.4） years. Their underlying diseases included cardiovascular and cerebrovascular diseases（23 patients）， chronic pulmonary disease（3 patients）， digestive disease（2 patients）， diabetes mellitus（3 patients）， and chronic kidney disease（1 patients）. Before admission， 22 patients received oral medication. The initial symptoms were fever and cough. The peak body temperature averaged（38.4±0.6）℃ The mean time from symptom onset to hospitalization was 15.0±7.7 days. The clinical classification was mainly severe type in 26 patients（87%）. Laboratory examination revealed lower lymphocyte count（0.7±0.2）×109/L， and higher blood D-D dimer lever（6.9±13）μg/L. Serum lactate dehydrogenase（LDH） significantly increased（310±136）U/L. Serum C-reactive protein（61±52）mg/L and erythrocyte sedimentation rate（ESR）（66±38）mmol/L slightly increased. Imaging performance revealed that diffuse lesions were located in bilateral pulmonary parenchyma（22 patients） and in single pulmonary parenchyma（7 patients）. Ground-glass opacity was found in all the patients， and the average number of CT examination during hospitalization was 3.5±1.3. Viral load revealed that nucleic acid in nasopharyngeal swabs of 30 patients was all positive， nucleic acid in the feces of 6 patients was positive， and nucleic acid in nasopharyngeal swab of 1 patient was positive， whose nucleic acid in alveolar lavage fluid was negative. Serum IgG antibody level was（157.5±29.2）AU/mL and IgM antibody level was（69.0±148.7）AU/mL. Complications included ARDS in 5 patients， AKI in 5 patients， cardiac injury in 3 patients， shock in 2 patients， nosocomial infection in 3 patients， coagulation disorder in 3 patients， and gastrointestinal bleeding in 3 patients. Finally， 5 patients received non-invasive mechanical ventilation and 2 patients received invasive mechanical ventilation. Another 2 patients underwent CRRT and 1 patient received CRRT plus ECMO. Of the 3 patients with critical type， 2 died and 1 survived. There were 25 patients who turned from severe type into normal type/light type， and 1 patient finally died（turned from severe type into critical type）. In the end， 15 patients were cured and discharged. The average time of viral nucleic acid from positive to negative was 12.4±5.6 and the average time of lesion absorption in computer tomography was 16.9±5.8 days. The total hospital stay was 22.9±8.1 days， and the 28-day mortality rate was 6.7%. 【Conclusion】 COVID-19 in elderly patients is mostly severe and its initial symptoms are still fever and cough. Patients should be immediately hospitalized when symptoms develop. The time of viral nucleic acid transformation and imaging improvement is longer than that of others. The mortality in critically ill patients is higher than that of others. Clinicians should pay more attention to the elderly people.

The 487th case: prominent eyes, headache, blurred vision / 中华内科杂志

One 51 years old man was admitted to the rheumatology department with a history of prominent eyes, headache and blurred vision for half year. The main manifestations included retrobulbar inflammatory pseudotumor and retroperitoneal fibrosis. He was initially diagnosed as granulomatosis with polyangiitis. Prednisone and cyclophosphamide were administrated and effective. New mass of dura mater and osteosclerosis presented during follow up. Finally Erdheim Chester disease(ECD) was diagnosed by biopsy and pathological examination. Vemurafenib, a v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) inhibitor, 480 mg was given twice a day. The patient′s condition is stable and still in follow-up. Although ECD is a rare histiocytosis, clinicians should pay attention to its manifestations and differential diagnoses.