3D-printed methacrylated gelatin scaffold loaded with fibroblasts promoting angiogenesis in vitro / 中国组织工程研究

BACKGROUND:Combining seed cells with 3D bioprinting technology enables the specific construction of various tissues and organs to meet the demands of tissue repair.However,further research is needed on the promotion of angiogenesis in damaged tissues. OBJECTIVE:By cultivating a 3D scaffold structure of methacrylated gelatin loaded with fibroblasts,obtaining the supernatant,and mixing it in different proportions with a complete culture medium to simulate the cellular microenvironment during tissue repair,this study aimed to explore the role of various cellular microenvironments in promoting angiogenesis in endothelial cells. METHODS:A methacrylated gelatin scaffold structure loaded with fibroblasts was prepared using an extrusion-based 3D bioprinting process.Hydrogel scaffold extract was prepared and mixed with a complete culture medium in ratios of 1:1,1:2,and 1:4 to obtain conditioned medium.Mouse embryonic fibroblasts BALB3T3 and human umbilical vein endothelial cells were co-cultured with complete medium(control group)and hydrogel scaffold extract,respectively.Cell proliferation was assessed using the CCK-8 assay and cell viability was analyzed using live/dead staining.Three kinds of conditioned medium and complete medium(control group)were used to co-culture with human umbilical vein endothelial cells for tube formulation assay,vascular genetic testing,and immunofluorescence staining of CD31. RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the methacrylated gelatin scaffold exhibited a porous structure,and rheological results demonstrated excellent mechanical properties of the hydrogel.CCK-8 assay and live/dead cell staining showed that the hydrogel scaffold extract had no obvious cytotoxicity.(2)Tube formulation assay indicated that the hydrogel showed the total length of cell tubules in 1:1 conditioned medium group was smaller than that in the control group(P<0.05).There were no statistical differences among the four groups in the number of vascular branches formed by endothelial cells(P>0.05).(3)qRT-PCR results showed that for vascular endothelial growth factor mRNA expression,the 1:2 conditioned medium group was lower than the 1:1 conditioned medium group on day 1(P<0.01).On day 3,the expression level of vascular endothelial growth factor in the 1:2 conditioned medium group was higher than that in the control group(P<0.01).On day 5,the cytokine expression level in the 1:2 conditioned medium group was significantly higher than that in the other three groups(P<0.01 or P<0.000 1).The expression in the 1:1 conditioned medium group was significantly lower than that in the other three groups(P<0.05 or P<0.01).On day 1,the expression level of basic fibroblast growth factor in the 1:1 conditioned medium group was significantly higher than that in the control group and 1:4 conditioned medium group(P<0.01,P<0.05).The expression was higher in the 1:2 conditioned medium group than that in the control group(P<0.05).On day 3,the expression levels of cytokines in the 1:4 conditioned medium group was higher than that in the control group(P<0.05).(4)On day 3,the expression of CD31 in the 1:2 conditioned medium group was higher than that in the control group and the 1:4 conditioned medium group(P<0.05).(5)The results indicate that the resulting conditioned media can simulate the microenvironment of vascular regeneration after tissue damage,promoting the vascularization process of endothelial cells.The best promotion of vascularization in endothelial cells was observed when the ratio of supernatant to complete culture medium was 1:2.

Improvement of Skin Barrier and Anti-inflammatory Mechanism of Huangliansan on Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect of Huangliansan on atopic dermatitis （AD） model mice induced by 2， 4-dinitrochlorobenzene （DNCB）. MethodA total of 42 male BALB/c mice were randomly divided into normal group， model group， hydrocortisone group， low， medium， and high-dose groups （0.3， 0.6， 1.2 g·kg-1） of Huangliansan oil， and water extract group （0.6 g·kg-1） of Huangliansan. In addition to the normal group， DNCB was applied on the back of mice in other groups to establish the AD model. On the 15th day after DNCB stimulation， each group was given the corresponding drug or solvent， and the changes in skin lesions， dermatitis score， and frequency of scratching were observed and recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the skin and spleen. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of filaggrin （FLG）， lorophane （LOR）， and involucrin （IVL） in skin， as well as immunoglobulin E （lgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interferon-γ （IFN-γ） in spleen. ResultCompared with the normal group， the model group showed symptoms of skin swelling and scab， and the score of dermatitis， the frequency of scratching， and the spleen index were increased （P<0.05）. The expression levels of FLG， LOR， and IVL in skin tissue were significantly decreased （P<0.01）， and the mRNA expressions of IgE， IL-4， IL-6， IL-1β， and TNF-α in the spleen were significantly increased， while the expression level of IFN-γ was significantly decreased （P<0.01）. Compared with the model group， the symptoms of skin erythema， scaly， and scab of mice in each drug group were alleviated to varying degrees， and the score of dermatitis， the frequency of scratching， and the spleen index were decreased （P<0.05， P<0.01）. In addition， the expression levels of FLG， LOR， and IVL in the skin of mice in the drug group were increased （P<0.05， P<0.01）， and the mRNA expression of IgE， IL-4， IL-6， IL-1β， and TNF-α in spleen were decreased. IFN-γ was increased （P<0.05， P<0.01）， and the lesions of the skin and spleen were improved to varying degrees. The medium-dose group of Huangliansan oil and hydrocortisone group had the most obvious manifestations （P<0.05， P<0.01）. The indexes in the medium-dose group of Huangliansan oil were better than those in the water extract group of Huangliansan. ConclusionHuangliansan may improve the expression level of skin barrier protein， inhibit the expression of helper T cell 2 （Th2）-related inflammatory factors， increase the expression of helper T cell 1 （Th1） inflammatory factors， restore the skin barrier function and Th1/Th2 balance in the spleen， regulate the inflammatory response in the spleen of AD mice， and thus relieve AD. Huangliansan oil is more effective than water extract.

The Influence of In Vitro Diagnostic Technology on Health and Its Application in Economic Evaluation / 中国卫生经济

In vitro diagnostic technology is an important aid for disease prevention,treatment,and prognostic monitoring.The de-velopment of its new technologies,methods and products is of great significance for improving medical quality and protecting public health.On the basis of exploring the mechanism of health impact of in vitro diagnostic technology,it takes dry chemical method and wet chemical method as an example,and compares the economy of the two diagnostic technologies for hyperkalemia diagnosis from the perspective of health system,with a view to draw references for the practical application and evaluation of new in vitro diagnostic techniques,methods and products in the future.

Role of new serological markers in evaluating the progression of liver disease in patients with chronic HBV infection and normal aminotransferases / 临床肝胆病杂志

Antiviral therapy is the basic treatment method for improving prognosis recommended in the management guidelines of chronic hepatitis B in China and globally. For patients with chronic HBV infection and normal transaminases, it is difficult in clinical practice to accurately evaluate the progression of hepatitis and identify suitable patients who need antiviral therapy. In order to objectively and accurately evaluate the degree of liver inflammatory activity in such patients, more and more noninvasive evaluation indicators have been used in addition to conventional liver biopsy. This article reviews the new serological indicators that can reflect the degree of liver inflammation and/or fibrosis in patients with chronic HBV infection and normal aminotransferase levels, hoping to provide a reference for antiviral decision-making in these patients.

Effectiveness of comprehensive intervention on primary dental caries in 3-year-old children in Bengbu / 中国学校卫生

Objective@#To explore the effectiveness of the comprehensive intervention on prevention of deciduous primary caries in 3-year-old children, so as so provide reference for the prevention, health care and treatment of oral caries.@*Methods@#Three-year-old children selected by drawing lots from 10 public kindergartens in 5 districts of Bengbu were examined in 2021, and were randomly divided into intervention group ( n =300) and control group ( n =300). During the initial examination, caries loss (dmf) including dental caries, missing teeth, filling teeth were assessed in the two groups. At the initial examination, the intervention group received caries intervention while no intervention was administered in the non-intervention group until half a year later. Intervention measures included education, diet, self-cleaning and fluoride application intervention. The number of cases and the mean of caries loss in the two groups were compared by χ 2 test.@*Results@#Before the intervention, 43 children in the control group suffered from caries, with 88 dmf, including 44 dmf for boys and 44 dmf for girls. There were 45 children in the intervention group, with 101 dmf, including 49 dmf for boys and 52 dmf for girls. There was no significant difference in the number of dmf between the intervention group and the control group ( χ 2=0.91, P >0.05), and there was no significant difference in the prevalence rate (15.0%, 14.3%, χ 2=0.05, P >0.05). After the intervention, there were 26 new dental caries and 43 dmf in intervention group, including 25 dmf for boys and 18 dmf for girls. In the control group, there were 83 new dental caries and 168 dmf, including 72 dmf for boys and 96 dmf for girls. Compared with the control group, the new dmf in the intervention group was significantly different ( χ 2=75.38, P < 0.05). The number of new dental caries patients in the intervention group was significantly different from that in the control group ( χ 2=36.42, P <0.05).@*Conclusion@#Comprehensive interventions to prevent dental caries can significantly reduce the incidence of primary teeth caries in children. It is suggested to intervene dental caries as early as possible to reduce the incidence of dental caries and other oral diseases.

Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin / 中华预防医学杂志

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.

Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration / 中华预防医学杂志

To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.

Analysis of the clinical characteristics and misdiagnosis of area postrema syndrome manifesting as intractable nausea, vomiting, and hiccups in neuromyelitis optica spectrum disorders / 中华内科杂志

Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.

Effects of adjuvant trastuzumab on long-term survival of T1N0M0 stage human epidermal growth factor receptor 2 positive breast cancer: a real-world study / 中华肿瘤杂志

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group (P<0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group (P>0.05). Multivariate analysis showed that histological grade (HR=2.927, 95 CI: 1.476, 5.805; P=0.002), vascular invasion (HR=3.410, 95 CI: 1.170, 9.940; P=0.025), menstrual status (HR=3.692, 95 CI: 1.021, 13.344, P=0.046), and chemotherapy (HR=0.238, 95 CI: 0.079, 0.720; P=0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%(P=0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%(P=0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Clinical analysis of inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopy / 中华外科杂志

Objective: To examine the safety and effectiveness of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE). Methods: Totally 269 patients admitted to the Anhui Provincial Hospital of Anhui Medical University who underwent IVMTE (IVMTE group, n=47) or thoracoscopy combined with minimally invasive Mckeown esophageal cancer resection (MIME group, n=222) from September 2017 to December 2021 were analyzed retrospectively. There were 31 males and 16 females in IVMTE group, aged (68.6±7.5) years (range: 54 to 87 years). There were 159 males and 63 females in MIME group, aged (66.8±8.8) years (range: 42 to 93 years). A 1∶1 match was performed on both groups by propensity score matching, with 38 cases in each group. The intraoperative conditions and postoperative complication rates of the two groups were compared by t test, Wilcoxon rank, χ2 test, or Fisher exact probability method. Results: Patients in IVMTE group had less intraoperative bleeding ((96.0±39.2) ml vs. (123.8±49.3) ml, t=-2.627, P=0.011), shorter operation time ((239.1±47.3) minutes vs. (264.2±57.2) minutes, t=-2.086, P=0.040), and less drainage 3 days after surgery (85(89) ml vs. 675(573) ml, Z=-7.575, P<0.01) compared with that of MIME group. There were no statistically significant differences between the two groups in terms of drainage tube-belt time, postoperative hospital stay, and lymph node dissection stations and numbers (all P>0.05). The incidence of Clavien-Dindo grade 1 to 2 pulmonary infection (7.9%(3/38) vs. 31.6%(12/38), χ²=6.728, P=0.009), total complications (21.1%(8/38) vs. 47.4%(18/38), χ²=5.846, P=0.016) and total lung complications (13.2%(5/38) vs. 42.1%(16/38), χ²=7.962, P=0.005) in the IVMTE group were significantly lower. Conclusion: Inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopic esophagectomy is safe and feasible, which can reach the same range of oncology as thoracoscopic surgery.

On-Site Assessment of a Cryogenic Disinfectant for the Alpine Environment and Outer Packaging of Frozen Items / 生物医学与环境科学（英文）

OBJECTIVE@#To study the effectiveness and feasibility of cryogenic disinfectants in different cold scenarios and analyze the key points of on-site cryogenic disinfection.@*METHODS@#Qingdao and Suifenhe were selected as application sites for the manual or mechanical spraying of cryogenic disinfectants. The same amount of disinfectant (3,000 mg/L) was applied on cold chain food packaging, cold chain containers, transport vehicles, alpine environments, and article surfaces. The killing log value of the cryogenic disinfectant against the indicator microorganisms ( Staphylococcus aureus and Escherichia coli) was used to evaluate the on-site disinfection effect.@*RESULTS@#When using 3,000 mg/L with an action time of 10 min on the ground in alpine regions, the surface of frozen items, cold-chain containers, and cold chain food packaging in supermarkets, all external surfaces were successfully disinfected, with a pass rate of 100%. The disinfection pass rates for cold chain food packaging and cold chain transport vehicles of centralized supervised warehouses and food processing enterprises were 12.5% (15/120), 81.67% (49/60), and 93.33% (14/15), respectively; yet, the surfaces were not fully sprayed.@*CONCLUSION@#Cryogenic disinfectants are effective in disinfecting alpine environments and the outer packaging of frozen items. The application of cryogenic disinfectants should be regulated to ensure that they cover all surfaces of the disinfected object, thus ensuring effective cryogenic disinfection.

Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review / 中国中药杂志

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Clinical characteristics and genetic analysis of four patients with central hypothyroidism due to IGSF1 gene variants / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene.@*METHODS@#Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed.@*RESULTS@#All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up.@*CONCLUSION@#Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.

Acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP).@*METHODS@#Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated.@*RESULTS@#Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions.@*CONCLUSION@#Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.

Correlation between spatial inclination of Blumensaat line and anterior cruciate ligament injury based on EOS biplanar 3D imaging system / 中国骨伤

OBJECTIVE@#To explore correlation between femoral mechanical axis and Blumensaat line (FMBL) angle of knee joint (angle between Blumensaat line and femoral mechanical axis), α angle (angle between Blumensaat line and axis of distal femur in sagittal plane) on EOS biplane imaging and non-contact anterior cruciate ligament(ACL) injury, and evaluate angle for its accuracy in predicting the populations prone to non-contact ACL injury.@*METHODS@#From February 2018 to October 2020, EOS imaging and clinical data from 88 patients (176 knees) with unilateral non-contact ACL injury were retrospectively analyzed, including 53 males and 35 females, aged from 18 to 45 years old with an average of (30.3±6.2) years old, 48 patients on the left side and 40 patients on the right side. The patients were divided into ACL-affected group and ACL-health group according to side of ACL injuries, and 51 patients (51 knees) with non-ACL identified from EOS database were included in normal control group, including 28 males and 23 females, aged from 20 to 44 years old with an average of (31.6±5.5) years old, 26 patients on the left side and 25 patients on the right side. Full-length EOS imaging of skeleton extremitatis inferioris among three groups were reconstructed to 3D images of skeletal system with EOS software, and then FMBL angle and α angle were measured on the images. Univariate binary Logistic regression analysis was performed to determine the influence of the univariate(FMBL angle or α angle) on ACL status(normal or torn). And the angle cutoff value for univariate was selected based on receiver operating characteristics curve (ROC) to got the best accuracy.@*RESULTS@#There was no statistically significant difference in age, gender and side distribution between ACL-injured group and normal control group(P>0.05). Statistical analyses (one-way ANOVA) indicated no significant difference in FMBL angle between ACL-injured knee group (32.8±2.3)° and ACL-injured contralateral knee group(32.5±2.3)°(P>0.05), but the values between two groups were significantly lower than that in normal control group (37.0±2.0)°(P<0.001). There was no statistically significant difference in α angle among three groups (P>0.05). Univariate binary Logistic regression analysis demonstrated that FMBL angle was risk factor for non-contact ACL injury[OR=0.433, 95%CI(0.330, 0.569), P<0.001]. The area under ROC curve for FMBL angle was 0.909[95%CI(0.861, 0.958), P<0.001], and the sensitivity and specificity were 70.5% and 98.0% respectively, cut-off value was 33.7°.@*CONCLUSION@#FMBL angle formed by Blumensaat line and femoral mechanical axis is one of the risk factors for non-contact ACL injury and has good predictive accuracy. The general population with FMBL angle below 33.7° may be increased risk for ACL injury.

Effect of posture on total hip arthroplasty through direct anterior approach / 中国骨伤

OBJECTIVE@#To investigate the effect of different postures on direct anterior approach(DAA) total hip arthroplasty.@*METHODS@#Total of 94 patients who underwent DAA total hip arthroplasty from July 2016 to June 2020 were retrospectively analyzed. They were divided into two groups according to different positions during the operation, including 45 cases in lateral position and 49 cases in supine position (with the aid of stent). The general data such as gender, affected limb, body mass index(BMI), incision length, operation time, intraoperative bleeding volume, drainage volume 24 hours after operation, hemoglobin difference before and after operation, first landing time after operation, postoperative hospitalization time, postoperative complications, visual analogue scale(VAS) at 1 day, 1, 2 weeks, 1, 3 and 6 months after operation, Harris score at 1, 2 weeks, 1, 3 and 6 months after operation were observed and compared between the two groups.@*RESULTS@#Patients in both groups were followed up for 6 to 12 months with an average of (8.31±2.22) months. There was no significant difference between two groups in gender, affected limb, age, height, weight, body mass index(BMI), preoperative VAS score and preoperative Harris score(P>0.05). The incision length, operation time, intraoperative bleeding volume, 24-hour drainage volume, hemoglobin difference before and after operation, first time to the ground and postoperative hospitalization time of patients in supine position (assisted by stent) group were all better than those in lateral position group(P<0.05);There was no significant difference in the number of blood transfusions during and after operation(P=0.550). There was no significant difference in anteversion angle and abduction angle in the supine position(with the aid of stent) group during and after operation (P=0.825, P=0.066);There was significant difference in anteversion angle and abduction angle in the lateral position group during and after operation(P<0.05). VAS of patients in supine position (assisted by stent) group were lower than those in lateral position group at 1 day, 1, 2 weeks and 1 month after operation(P<0.05), and there was no statistical difference between two groups at 3 and 6 months after operation(P>0.05). Harris scores of patients in supine position(assisted by stent) group were higher than those in lateral position group at 1 week, 1 month and 3 months after operation(P<0.05), and there was no significant difference between two groups at 6 months after operation(P>0.05).@*CONCLUSION@#Compared with the lateral position, the supine position DAA total hip arthroplasty has the advantages of small incision, short operation time, less bleeding, early landing time, short hospitalization time, and small intraoperative acetabular cup position judgment error. It has the advantage of fast postoperative recovery, but the recovery of hip joint function is the same after 6 months.

Electrotaxis of alveolar epithelial cells in direct-current electric fields / 中华创伤杂志(英文版)

PURPOSE@#This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.@*METHODS@#AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis.@*RESULTS@#The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.@*CONCLUSION@#EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

How to effectively manage the refractory coronary thrombus? A systemic mini-review / 老年心脏病学杂志（英文版）

The main management principle for patients with coronary thrombus should be "more removal and less implantation". Routine thrombus aspiration (TA) is ineffective for intracoronary thrombus or high residual thrombus burden after TA and may result in a refractory coronary thrombus. It is unwise to implant a stent in the vessel with high residual thrombus, which is associated with no-reflow, impaired microvascular perfusion, and consequently worse clinical outcomes. Therefore, increasing the efficiency of TA during percutaneous coronary intervention procedures, especially under some conditions of refractory coronary thrombus, is very important to restore myocardial reperfusion and improve microvascular dysfunction early. In the present work, we aimed to demonstrate the factors that may affect TA efficiency and introduce several highly effective approaches to treat refractory coronary thrombus.

Immunoprotective effect of recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice / 中国血吸虫病防治杂志

Objective To evaluate the immunoprotective effect of active immunization with recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice. Methods Female BALB/c mice at 6 weeks of age, each weighing approximately 20 g, were divided into the recombinant protein immunization group, the infection control group and the normal control group, of 25, 18, 15 mice in each group, respectively. Mice in the recombinant protein immunization group were given active immunization with recombinant BmPPIase protein, and 18 mice with the highest antibody titers were intraperitoneally injected with 100 μL of B. microti-infected whole blood 2 weeks after the last immunization. Mice in the infection control group were intraperitoneally injected with 100 μL of B. microti-infected whole blood, while 15 mice in the normal control group received no treatment. Blood samples were collected from mice in the recombinant protein immunization group and the infection control group on days 0 to 30 post-immunization for detection of B. microti infection, and blood samples were collected on days 0, 7, 14, 21, and 28 post-immunization for routine blood tests with a blood cell analyzer and for detection of serum cytokines using cytometric bead array. Results Anti-BmPPIase antibodies were detected in 25 mice in the recombinant protein immunization group 2 weeks after the last immunization, with titers of 5 × 103 to 8 × 104. B. microti infection rate peaked in mice in both the recombinant protein immunization and the infection control group on day 7 post-immunization, with positive infection rates of 13.3% and 50.0%, and there were significant differences between the two groups in terms of B. microti infection rate on days 3 (χ2= 113.18, P < 0.01), 5 (χ2 = 475.22, P < 0.01), 7 (χ2 = 465.98, P < 0.01) and 9 post-infection (χ2= 18.71, P < 0.01), while the B. microti infection rate tended to be 0 in both groups on day 11 post-immunization. Routine blood tests showed higher red blood cell counts [(5.30 ± 0.50) × 1012 to (9.87 ± 0.24) × 1012 counts/L)] and hemoglobin levels [(89.67 ± 22.80) to (148.60 ± 3.05) g/L)] in the recombinant protein immunization group than in the infection control group on days 0 to 28 post-immunization. Cytometric bead array detected higher serum interferon-γ [(748.59 ± 17.56) to (3 858.28 ± 1 049.10) fg/mL], tumor necrosis factor-α [(6 687.34 ± 1 016.64) to (12 708.13 ± 1 629.79) fg/mL], interleukin (IL)-6 [(611.05 ± 75.60) to (6 852.68 ± 1 554.00) fg/mL] and IL-17a [(167.68 ± 185.00) to (10 849.27 ± 355.40) fg/mL] and lower IL-10 levels [(247.65 ± 138.00) to (18 787.20 ± 2 830.22) fg/mL] in the recombinant protein immunization group than in the infection control group during the study period. Conclusions Recombinant BmPPIase protein induces up-regulation of interferon-γ, tumor necrosis factor-α and presents a high immunoprotective activity against B. microti infection in mice, which is a potential vaccine candidate protein.