Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism / 中国药理学通报

Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Clinical effect of cross positioning method for correcting low and moderate astigmatism during small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical outcomes of using the cross-positioning method for correcting low and moderate astigmatism during small incision lenticule extraction(SMILE)surgery with Alpins vector analysis.METHODS: A total of 50 patients(81 eyes)with low and moderate astigmatism with the rule ≤1.50 D who underwent SMILE surgery at the laser myopia treatment center of Xi'an No.1 Hospital from May 2022 to November 2022 were included in the prospective randomized controlled study, and they were divided into two groups according to the random table, with 25 case(41 eyes)in cross-positioning group and 25 cases(40 eyes)in control group. In the cross-positioning group, the patients' head position was adjusted based on the cross intersection lines before the standard SMILE procedure, aligning the lateral canthi with the horizontal line and the midpoint of the eyebrows and the nose bridge with the vertical line. Postoperative visual acuity and refractive results at 3 mo were observed in both groups, and astigmatic changes were analyzed and evaluated using the Alpins vector analysis method.RESULTS: During the follow-up period, 6 cases(11 eyes)in the cross-positioning group were lost to follow-up, while in the control group, 8 cases(14 eyes)were lost to follow-up, with 19 cases(30 eyes)and 17 cases(26 eyes)finally included in the cross-positioning group and the control group, respectively. At 3 mo postoperatively, the uncorrected visual acuity(UCVA)of both groups' operated eyes was ≥1.0, and no serious complications occurred, with no significant differences in UCVA, best corrected visual acuity(BCVA), spherical power, and spherical equivalent between the cross-positioning group and the control group(all P&#x0026;#x003E;0.05). The cylindrical power in the cross-positioning group was 0.00(0.00, 0.00)D, which was lower than -0.13(-0.50, 0.00)D in the control group(P=0.01). The vector analysis results showed that the difference vector(DV)in the cross-positioning group was lower than that in the control group [0.00(0.00, 0.00)vs 0.13(0.00, 0.50), P=0.01], and the index of success(IOS)was better than that of the control group [0.00(0.00, 0.00)vs 0.18(0.00, 0.77), P&#x0026;#x003C;0.01]. At 3 mo postoperatively, 26(87%)and 15(58%)eyes in the cross-positioning group and control groups achieved an angle of error(AE)within ±5°, respectively.CONCLUSION: The cross positioning method was used to calibrate the patients' head position during SMILE surgery, which reduced the axial position error and improved the accuracy of SMILE in correcting low and moderate astigmatism.

Corrective effect of femtosecond laser assisted laser in situ keratomileusis Xtra on patients with moderate to high myopia after 2a postoperatively / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P&#x0026;#x003C;0.01), and there was no difference in UCVA and SE between the two groups(P&#x0026;#x003E;0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P&#x0026;#x003C;0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P&#x0026;#x003C;0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.

Structurally novel HDAC inhibitors based on the trans-β-arylacryl tetrahydroisoquinoline scaffold: the design, synthesis, and anti-cancer activity / 药学学报

In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1,2,3,4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC50 at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC50 = 0.89 μmol·L-1; HCT116, IC50 = 0.49 μmol·L-1) to that of vorinostat (SAHA).Besides,13e, with the most potent HDAC1 enzymatic activity (IC50 = 3.8 nmol·L-1), also displayed attractive cellular activity (A549, IC50 = 1.74 μmol·L-1; HCT116, IC50 = 2.43 μmol·L-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Comparison of the effects between toric-designed and spherical orthokeratology for the control of moderate-to-low myopia in adolescents / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the control effects between toric-designed orthokeratology and spherical orthokeratology on adolescents with moderate-to-low myopia.METHODS: The clinical data of 169 adolescents(290 eyes)with moderate-to-low myopia in Jiayuan Outpatient Department of Shanghai Demu Ophthalmology from July 2020 to June 2021 were analyzed retrospectively. The patients were divided into toric group and spherical group according to the type of orthokeratology, with 81 cases(135 eyes)and 88 cases(155 eyes)respectively. The changes of visual acuity and ocular axis before and after treatment were recorded to evaluate the therapeutic effect.RESULTS: The uncorrected visual acuity of both groups significantly improved at 1a after treatment(P&#x003C;0.01), and the axial length increased compared to that before treatment(P&#x003C;0.01). But there were no significant differences in uncorrected visual acuity(0.014±0.043, 0.017±0.047LogMAR)and axial growth(0.18±0.22, 0.19±0.22mm)between the two groups(P&#x003E;0.05).CONCLUSION: Both toric-designed orthokeratology and spherical orthokeratology can improve the uncorrected visual acuity of adolescents with low-to-moderate myopia, and there is no significant difference in controlling effect on myopia.

Status and challenges of neoadjuvant immunotherapy for hepatocellular carcinoma / 中华外科杂志

With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.

Analysis of the status of excess heart age and its risk factors among residents aged 35 to 64 years in China / 中华预防医学杂志

Objective: To analyze the status of excess heart age and its risk factors among Chinese residents aged 35 to 64 years. Methods: The study subjects were Chinese residents aged 35 to 64 years who completed the heart age assessment by WeChat official account"Heart Strengthening Action"through the internet from January 2018 to April 2021. Information such as age, gender, body mass index (BMI), blood pressure, total cholesterol (TC), smoking history, and diabetes history was collected. The heart age and excess heart age were calculated according to the characteristics of individual cardiovascular risk factors and the heart aging was defined as excess heart age≥5 years and 10 years respectively. The heart age and standardization rate were calculated respectively based on the population standardization of the 7th census in 2021.CA trend test was used to analyze the changing trend of excess heart age rate and population attributable risk (PAR) was used to calculate the contribution of risk factors. Results: The mean age of 429 047 subjects was 49.25±8.66 years. The male accounted for 51.17% (219 558/429 047) and the excess heart age was 7.00 (0.00, 11.00) years. The excess heart age rate defined by excess heart age≥5 years and≥10 years was 57.02% (the standardized rate was 56.83%) and 38.02% (the standardized rate was 37.88%) respectively. With the increase of the age and number of risk factors, the excess heart age rate of the two definitions showed an upward trend according to the result of the trend test analysis (P<0.001). The top two risk factors of the PAR for excess heart age were overweight or obese and smoking. Among them, the male was smoking and overweight or obese, while the female was overweight or obese and having hypercholesterolemia. Conclusion: The excess heart age rate is high in Chinese residents aged 35 to 64 years and the contribution of overweight or obese, smoking and having hypercholesterolemia ranks high.

Epidemiological characteristics of human adenovirus 2, 3 and 7 genetypes in hospitalized children with respiratory infection in a hospital of pediatric in Hebei Province from 2018 to 2020 / 中华预防医学杂志

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ2 test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ2=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ2=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ2=20.438, P<0.01; χ2=42.105, P<0.01; χ2=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ2=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.

Relationship between uric acid and coronary atherosclerotic heart disease in adults / 公共卫生与预防医学

Objective To analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.

Research on friction and wear behaviors of silicon-lithium spray coating on zirconia ceramics / 北京大学学报(医学版)

OBJECTIVE@#To study microstructure, friction and wear behaviors of silicon-lithium spray coating on the surface of zirconia ceramics and to preliminarily evaluate its esthetic so as to provide support and guidance for the clinical application.@*METHODS@#Zirconia ceramic specimens were randomly divided into three groups: coating group (two subgroups), polishing group (two subgroups), and glazing group (four subgroups), with 10 samples in each subgroup. The two subgroups of coating group were the zirconia ceramics with the untreated and preliminary polishing surfaces sprayed with silicon-lithium coating, respectively. The two subgroups of polishing group were preliminary polishing and fine polishing of zirconia ceramics, respectively. The four subgroups of glazing group were preliminarily polished zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively; and untreated zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively. The above 8 subgroups of zirconia ceramic specimens were used as friction pairs with 80 steatite ceramics for 50 000 chewing cycles under 50 N vertical load and artificial saliva lubrication using chewing simulation. Scanning electron microscope was used to observe the microstructure of the surface and section of the coating group, and the thickness of the coating and glazing were measured. The linear roughness of the coating and polishing groups was mea-sured using a laser confocal scanning microscope. Vickers hardness was measured using a microhardness tester and the esthetic of zirconia ceramic full crown sprayed with silicon-lithium coating was preliminarily evaluated. White light interferometer was used to measure the width, the maximum depth and the volume of the wear scars of each group, and the wear depth of steatite ceramics and wear rate of zirconia ceramic specimens were calculated. Kruskal-Wallis nonparametric test and Dunn's multiple comparisons test were used to analyze the wear depth of each group (α=0.05).@*RESULTS@#The microstructures of the silica-lithium spray coatings on the untreated and preliminarily polished zirconia ceramic surfaces showed the protruding defects, and the line roughness of coating group was larger than that of the polishing group. The median thickness of the silica-lithium spray coating on the preliminarily polished zirconia ceramic was 13.0 μm (interquartile range, IQR: 11.6, 17.9), while that of the silica-lithium spray coating on the untreated zirconia ceramic was 4.4 μm (IQR: 4.1, 4.7). The Vickers hardness and wear rate of the coating group were between the polishing group and the glazing group. The wear depths of the wear scars of steatite ceramics were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference between glazing and polishing groups (P < 0.05). With the increase of polishing procedure, the wear depth of steatite ceramics decreased in each subgroups. The orders of maximum depth and volume of wear scars of zirconia ceramic were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference in the maximum depth of wear scars between glazing and polishing groups (P < 0.05).@*CONCLUSION@#The silica-lithium spray coating on the zirconia ceramic, can be used as a new method for zirconia ceramic surface treatment, because it can increase the esthetic of zirconia ceramics compared with polishing and reduce the wear of steatite ceramics compared with glazing.

Analysis of the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.

Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Membrane anatomy-based splenic hilar lymph node dissection for gastric cancer / 中华胃肠外科杂志

There is a consensus that selectively perform splenic lymph node dissection is necessary for high-risk patients with proximal gastric cancer to achieve radical treatment. However, there are still some outstanding issues that need to be solved during the practice of splenic lymph node dissection. These include poorly defined boundaries, technical difficulties, and blurred boundaries in No. 10 and No. 11 lymph nodes, etc. Membrane anatomy has achieved successful applications in the field of gastric and colorectal surgery in recent years. The study of membrane anatomy in the splenic hilum region is controversial due to the special location of the splenic hilum, which involves multiple organs and affiliated mesentery undergoing complex rotation, folding, and fusion during embryonic development. In this manuscript, we summarize the following points based on existing research and personal experience regarding membrane anatomy. 1. There is a membrane anatomical structure that can be used for lymph node dissection in the splenic hilum region. 2. The membrane structure in the splenic hilum region can be divided into two layers: the superficial layer is composed of the dorsal mesogastrium, and the deep layer is composed of Gerota fascia, the tail of the pancreas, and the mesentery of the transverse colon (from head to tail). 3. There is a loose space between the two layers that can be used for separation during surgery. The resection of the dorsal mesogastrium belongs to D2 dissection. The No. 10 lymph node in the deeper layer belongs to the duodenal mesentery, and the resection of the No.10 lymph node exceeds D2 dissection. The complete excision of the gastric dorsal mesentery is consistent with the D2+CME surgical mode proposed by Gong Jianping's group.

Completion rates of bundle treatment of among patients with sepsis shock in intensive care departments of hospitals in Jiangsu Province from 2016 to 2020 years / 中华内科杂志

Current clinical approaches for septic shock increasingly incorporate bundle treatment, a multi-component approach that uses a collection of tests and agents to assist in the identification and treatment of infection. The present study analyzed completion rates of 3 h and 6 h bundle treatment among patients with septic shock in intensive care units (ICUs) of hospitals in Jiangsu Province from 2016 to 2020, using data from the Jiangsu Provincial Intensive Care Medical Quality Control Center. Current approaches and factors affecting treatment completion were assessed.The completion rates of 3 h and 6 h bundle treatment in ICUs of all medical units in Jiangsu Province and in ICUs of hospitals of different levels were recorded. Analyses show that the completion rate of 3 h and 6 h bundle treatment for patients with septic shock in ICUs in Jiangsu Province increased year by year from 2016 to 2020.The completion rate of 3 h bundle treatment increased from 69.82% (3 604/5 162) to 82.47% (8 915/10 775) (all P<0.001). The completion rate of 6 h bundle treatment increased from 62.69% (3 236/5 162) to 72.54% (7 816/10 775) (all P<0.001). In addition, year by year, the completion rate of 3 h bundle treatment in ICUs in tertiary hospitals increased, from 69.80% (3 596/5 152) to 82.23% (7 375/8 969), while the completion rate of 6 h bundle treatment increased from 62.69% (3 230/5 152) to 72.18% (6 474/8 969) (all P<0.001). Completion rates in secondary hospitals also increased year by year, from 80.00% (8/10) to 85.27% (1 540/1 806) for 3 h treatment and from 60.00% (6/10) to 74.31% (1 342/1 806) (all P<0.001) for 6 h treatment. Completion rates for 3 h treatment in first-tier cities (83.99% (2 099/2 499)) and second-tier cities (84.68% (3 952/4 667)) was higher than in third-tier cities (79.36% (2 864/3 609)). The completion rate of 6 h bundle treatment gradually decreased in first-line (77.19% (1 929/2 499)), second-line (74.37% (3 471/4 667)), and third-line (66.94% (2 416/3 609)) cities (all P<0.001). The data collectively show that from 2016 to 2020, the completion rate of bundle treatment in septic shock patients in ICUs in Jiangsu Province improved significantly.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study / 中华妇产科杂志

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.