Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Therapeutic effect of sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autologous iliac bone graft of chronic calcaneal osteomyelitis / 国际外科学杂志

Objective:To analyze the therapeutic effect of sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft of chronic calcaneal osteomyelitis.Methods:A retrospective analysis was peformed in 29 patients with chronic calcaneal osteomyelitis treated with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from April 2013 to January 2020. There were 19 males and 10 females, with the age of (45.38±12.85) years, ranged from 22 to 67 years. The course of disease was (16.00±6.96) months, ranged from 6 to 36 months. The skin defect area was (41.9±15.9) cm 2, ranged from 11.8 to 86.8 cm 2. The causes of injury: 18 cases of high fall, 6 cases of traffic accidents, 3 cases of heavy rolling, the remaining 2 cases were machine strangulation and sharp stab wounds. The inflammatory markers [white blood cell (WBC), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C reactive protein (CRP)] and bone healing time were recorded before operation, 2, 4, 8 weeks and 6 months after operation. During the follow-up period, the flap texture, survival were observed, and the ankle-posterior foot function recovery was evaluated by the American Association of Foot and Ankle Surgery (AOFAS) score were observed before and after the operation, and the incidence of complications were recorded. The measurement data were expressed as mean±standard deviation ( ± s), and the t-test was used for inter-group comparison; the levels of WBC, ESR, PCT and CRP at different time points before and after operation were compared by repeated measurement ANOVA, and the LSD t-test was used for pairwise comparison. Results:All the 29 patients were followed up for (14.51±6.10) months, ranged from 6 to 30 months. All the flaps survived without abrasion, ulceration, or skin protrusion, and all patients could walk normally with shoes. There were 28 cases of stage I bone healing, with an average of (5.87±2.07) months, ranged from 3 to 12 months. The inflammatory indexes was significantly decreased at different time points after operation ( P<0.05). There was no significant difference between 6 months and 8 weeks after operation ( P>0.05), while there was significant difference at other time points ( P<0.05). The ankle-posterior foot score of AOFAS at 6 months after treatment was significantly higher than that before treatment (83.44±7.93 vs 55.37±8.07), the differences was statistically significant ( P<0.05). The clinical efficacy of foot function recovery was excellent in 12 cases, good in 15 cases and fair in 2 cases among 29 patients .The excellent and good rate was 93.1% (27/29). One patient recurred 1 month after operation and was re-implanted with antibiotic-loaded calcium sulfate mixed autogenous iliac bone after debridement, no recurrence was found. The total complication rate was 31.0%, but there was no significant impact on the patient's life in the later period. All patients returned to daily life and work. Conclusion:The treatment of chronic calcaneal osteomyelitis with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft can effectively control infection, reconstruct calcaneal and soft tissue structure, promote functional recovery of affected limb, and ultimately improve the patient′s quality of life.

Research on clinical efficacy of robot navigation assistance in the treatment of elderly femoral tuberosity fractures / 国际外科学杂志

Objective:To compare the clinical effects robot navigation assisted and conventional proximal femoral nail antirotation (PFNA) implantation and fixation in the treatment of elderly femoral trochanteric fractures.Methods:A total of 86 elderly patients with tuberosity fracture of the femur were admitted as research samples from January to March in 2022 in the Department of Trauma Orthopaedic, Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University, including 37 males and 49 females, who aged from 63 to 92 years, with an average age of (79.6 ± 6.9) years. All patients were treated with intramedullary nails (PFNA), 32 with dimensity robotic-assisted therapy (robot group) and 54 with traditional methods (conventional group). The length of incision, the number of intraoperative fluoroscopy, the amount of intraoperative blood loss, and the operation time were recorded. The occurrence of postoperative complications in the two groups was observed. The rate of excellent hip Harris score at 3 month after surgery was compared between the two groups. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as [ n(%)], and was conducted by Chi-square test or Fisher exact probability between groups. Results:All patients were followed up for 9 to 12 months, with an average of (10.6 ± 0.9) months. The incision length and tip apex distance (TAD) of the robot group were (3.40±0.82) cm and (21.85±1.44) mm, which were smaller than (4.82±0.75) cm and (26.83±1.75) mm in the conventional group ( P<0.05 for all). The number of intraoperative fluoroscopy and guide needle adjustment [(14.53±3.26) and 0 times] in the robot group were less than those in the conventional group [(20.67±4.84) and (2.83±1.42)] ( P<0.05). The intraoperative blood loss and drainage rate of the robot group were (87.03±9.41) and (46.40±8.91) mL, which were smaller than that of the conventional group [(110.00±12.52) and (69.62±10.22) mL] ( P<0.05). There was no significant difference in the number of days of hospitalization and operation time between the two groups ( P>0.05). The postoperative complication rate in the robot group was 9.4%, which was lower than that in conventional group (42.6%), and the difference was statistically significant ( χ2=11.88, P=0.036). The excellent rate of postoperative hip joint function in the robot group was 75.0%, and the conventional group was 66.7%, and there was no significant difference between the two groups ( χ2=0.66, P=0.416). Conclusion:Robot-assisted navigation downward PFNA surgery can have good clinical effect in the treatment of femoral tuberosity fracture in the elderly, which can reduce the number of surgical incisions and intraoperative fluoroscopy, and reduce the incidence of postoperative complications, which is helpful to achieve minimally invasive surgery and rapid recovery of elderly patients with femoral tuberosity fracture.

Comparison of acute shortening-lengthening and antibiotic calcium sulfate-loaded bone transport for the treatment of segmental tibial defects after trauma / 国际外科学杂志

Objective:To compare the clinical effects of acute shortening-lengthening technique with antibiotic calcium sulfate-loaded bone transport technique for the treatment of segmental tibial defects after trauma.Methods:The clinical data of 58 patients with large tibial defects treated by Ilizarov technique in Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from May 2014 to December 2019 were retrospectively analyzed. Thirty patients were treated by acute shortening-lengthening (group A), and they were divided into those who were successful in one-time shortening during operation (group A1) and those who needed gradual shortening after operation (group A2) according to different shortening conditions. And 28 patients by antibiotic calcium sulfate-loaded bone transport (group B). The external fixation time (EFT) and external fixation index (EFI) of the two groups were compared. Bone defect healing and limb functions were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Complications were compared by Paley classification. The measurement data of normal distribution were expressed as ± s, and t-test was used for comparison between groups; the count data were expressed as n(%), and the chi-square test, Fisher exact probability method or Mann-Whitney U test were used for comparison between groups. Results:Patients were followed for(27.5±5.1)months. There was no significant difference in EFT, EFI, bone defect healing and limb functions between the two groups( P>0.05). The incidence of Grade-Ⅱ[41.2% (7/17)], Grade-Ⅲ [47.1% (8/17)] pin-tract infection in group A1 and Grade-Ⅱ[46.2% (6/13)], Grade-Ⅲ pin-tract [53.8% (7/13)] in group A2 was significantly higher than those in group B[14.3% (4/28)], [17.9% (5/28)] ( P<0.05). The number of complications per capita in group A1 [(1.4±0.3) times/case] and in group A2 [(1.5±0.3) times/case]was significantly higher than that in group B [(1.1±0.5) times/case]. Conclusions:Patients can be cured successfully by both acute shortening-lengthening and bone transport techniques. Compared with acute shortening-lengthening group, the complication incidence in antibiotic calcium sulfate-loaded bone transport group was lower, especially, the infection-related complications. Therefore, antibiotic calcium sulfate-loaded bone transport technique has a greater application prospect in patients with large segmental bone defects caused by infection or osteomyelitis.

Anterolateral or Posteromedial Plate-Assisted Intramedullary Nailing for Fixation of Proximal Third Tibia Fractures: A Biomechanical Study / 医用生物力学

Objective To study the stability of plate-assisted intramedullary nailing for fixing proximal third tibiafractures, compare and observe biomechanical characteristics of anterolateral or posteromedial plate-assisted intramedullary nailing after fixation of proximal third tibia fractures. Methods Eight artificial tibia of 4th-generation sawbones were divided into two groups based on location of the assisted plate, namely, anterolateral plate group and posteromedial plate group, with 4 specimens in each group. Each two locking bolts were fixed to theintramedullary nail proximally and distally, and each three bicortical screws were fixed to the plate proximally and distally. The specimens were osteotomized with a 10-mm defect which located 0. 5 cm to the proximal locking bolt of intramedullary nail or 5-6 cm distally to the knee joint line, in order to simulate an AO/ OTA 41-A2 type proximal third tibia fracture after fixation of intramedullary nail. After osteotomy was finished, axial compression test, three point bending test, cyclic loading and overstress test were conducted by mechanical testing machine. The results of axial stiffness and three-point stiffness between two groups were compared and analyzed. Results Axial compression test showed that the average axial stiffness in posteromedial plate group was lower than that in anterolateral plate group, but no significantly statistical differences were found between the two groups. Three point bending test showed that the average bending stiffness in posteromedial plate group was significantly higher than that in anterolateral plate group when stimulating either varus stress (plate located at pressure side of the fracture, t = 3. 679, P<0. 05) or valgus stress (plate located at tension side of the fracture, t = 8. 975, P<0. 05). Conclusions Plate-assisted intramedullary nailing for fixation of proximal third tibia fractures can minimize the angulation malalignment, improve the stability of nailed proximal tibial fragment and allow the early weight bearing. Both anterolateral and posteromedial plate-assisted intramedullary nail can provide satisfactory axial stability for proximal third tibia fractures, while posteromedial plate-assisted intramedullary nail shows better bending stability than anterolateral plate in countering varus or valgus stress deformity. This study provides an essential basis for clinical decision making about plate-assisted intramedullary nailing for fixing proximal third tibia fractures.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Survival of Non-small Cell Lung Cancer Patients Treated with Fuzheng Gushe Therapy： A Real World Study / 中国实验方剂学杂志

ObjectiveTo analyze the long-term survival of non-small cell lung cancer （NSCLC） patients treated with Fuzheng Gushe therapy in the real world. MethodA retrospective cohort study was carried out with the NSCLC patients treated with Fuzheng Gushe therapy from January 2014 to December 2018 in Dongzhimen Hospital， Beijing University of Chinese Medicine as the integrated traditional Chinese medicine （TCM） and western medicine cohort. The NSCLC data from January 2011 to December 2015 in the Surveillance， Epidemiology， and End Results （SEER） database were downloaded as the western medicine cohort. The propensity score matching （PSM） was employed to balance the confounding factors between the groups， and comparable samples were obtained from the two groups. The Log-rank test was conducted to compare the overall survival between the groups and the survival curves were established. ResultThe integrated TCM and western medicine cohort and the western medicine cohort included 511 and 5 022 NSCLC patients， respectively. The age， sex， and chemotherapy had no significant differences between the two cohorts， while pathological type， lymph node metastasis （N）， distant metastasis （M）， surgery， and radiotherapy were different between the two cohorts （P<0.05）. After PSM， 122 comparable samples were obtained. The overall survival analysis showed that the total survival of the integrated TCM and western medicine cohort was better than that of the western medicine cohort （P<0.05）. The stratified survival analysis showed that the integrated TCM and western medicine cohort had survival advantages in females， males， the young， and adenocarcinoma， N+， and M+ patients （P<0.05）. ConclusionFuzheng Gushe therapy can significantly improve the overall survival of NSCLC patients， especially in the females， the males， the young， and the patients with adenocarcinoma， lymph node metastasis， and distant metastasis.

The Distribution and Significance of Activated T Cells and Lymphocyte Subsets in Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution of bone marrow lymphocyte subsets in patients with myelodysplastic syndrome(MDS),the proportion of activated T cells with immunophenotype CD3+HLA-DR+ in the lymphocytes and its clinical significance, and to understand the effects of different types of MDS, different immunophenotypes, and different expression levels of WT1 on the proportion of lymphocyte subsets and activated T cells.@*METHODS@#The immunophenotypes of 96 MDS patients, the subsets of bone marrow lymphocytes and activated T cells were detected by flow cytometry. The relative expression of WT1 was detected by real-time fluorescent quantitative PCR, and the first induced remission rate (CR1) was calculated, the differences of lymphocyte subsets and activated T cells in MDS patients with different immunophenotype, different WT1 expression, and different course of disease were analyzed.@*RESULTS@#The percentage of CD4+T lymphocyte in MDS-EB-2, IPSS high-risk, CD34+ cells >10%, and patients with CD34+CD7+ cell population and WT1 gene overexpression at intial diagnosis decreased significantly (P<0.05), and the percentage of NK cells and activated T cells increased significantly (P<0.05), but there was no significant difference in the ratio of B lymphocytes. Compared with the normal control group, the percentage of NK cells and activated T cells in IPSS-intermediate-2 group was significantly higher(P<0.05), but there was no significant difference in the percentage of CD3+T, CD4+T lymphocytes. The percentage of CD4+T cells in patients with complete remission after the first chemotherapy was significantly higher than in patients with incomplete remission(P<0.05), and the percentage of NK cells and activated T cells was significantly lower than that in patients with incomplete remission (P<0.05).@*CONCLUSION@#In MDS patients, the proportion of CD3+T and CD4+T lymphocytes decreased, and the proportion of activated T cells increased, indicating that the differentiation type of MDS is more primitive and the prognosis is worse.

Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism.@*METHODS@#Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot.@*RESULTS@#The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61.@*CONCLUSION@#Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.

Regulation of ischemic stroke by circadian rhythm and intervention by traditional Chinese medicine / 中国中药杂志

Circadian rhythm is an internal regulatory mechanism formed in organisms in response to the circadian periodicity in the environment, which modulates the pathophysiological events, occurrence and development of diseases, and the response to treatment in mammals. It significantly influences the susceptibility, injury, and recovery of ischemic stroke, and the response to therapy. Accumulating evidence indicates that circadian rhythms not only regulate the important physiological factors of ischemic stroke events, such as blood pressure and coagulation-fibrinolysis system, but also participate in the immuno-inflammatory reaction mediated by glial cells and peripheral immune cells after ischemic injury and the regulation of neurovascular unit(NVU). This article aims to link molecular, cellular, and physiological pathways in circadian biology to the clinical consequences of ischemic stroke and to illustrate the impact of circadian rhythms on ischemic stroke pathogenesis, the regulation of NVU, and the immuno-inflammatory responses. The regulation of circadian rhythm by traditional Chinese medicine is reviewed, and the research progress of traditional Chinese medicine intervention in circadian rhythm is summarized to provide a reasonable and valuable reference for the follow-up traditional Chinese medicine research and molecular mechanism research of circadian rhythm.

Endoscopic resection of type D trigeminal schwannoma through nasal sinus approach / 中华外科杂志

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.

Comparison of bone transport technique combined with bone grafting plus internal fixation versus simple bone transport technique for large segmental bone defects at lower limbs after trauma / 中华创伤骨科杂志

Objective:To compare the clinical efficacy between bone transport technique combined with bone grafting plus internal fixation and simple bone transport technique in the treatment of large segmental bone defects at lower limbs after trauma.Methods:A retrospective study was conducted to analyze the clinical data of 42 patients with large segmental bone defects at lower limbs after trauma who had been treated at Department of Trauma Orthopaedics, Honghui Hospital Affiliated to Medicine College, Xi'an Jiaotong University from September 2015 to September 2019. The patients were divided into 2 groups according to the different methods of repairing bone defects. In group A of 18 patients subjected to bone transport combined with bone grafting plus internal fixation, there were 11 males and 7 females with an age of (35.2±10.3) years, and 12 tibial defects and 6 femoral defects; in group B of 24 patients subjected to simple bone transport, there were 15 males and 9 females with an age of (37.3±9.4) years, and 17 tibial defects and 7 femoral defects. The external fixation time (EFT), external fixation index (EFI), total cure time and complications were recorded and compared between the 2 groups. At the last follow-up, the Ennecking score for limb functional recovery (score/total score 30) and Self-rating Anxiety Scale (SAS) were used to evaluate respectively the functional recovery of the limbs and postoperative anxiety.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). There was no statistically significant difference in the number of surgeries between the 2 groups ( P>0.05). The EFT [(5.9±1.5) months], EFI [(0.45±0.09) months/cm], total treatment time [(16.2±2.4) months], Ennecking score for limb functional recovery (87.0%±8.6%), SAS score [(43.2±9.0) points], and complications per capita [(0.4±0.2) times/case] in group A were significantly better than those in group B [(15.3±4.2) months, (1.19±0.28) months/cm, (19.7±3.5) months, (77.3%±9.2%), (58.2±9.3) points, and (1.2±0.5) times/case] (all P<0.05). Conclusion:In the treatment of large segmental bone defects at lower limbs, compared with simple bone transport technique, bone transport technique combined with bone grafting plus internal fixation has advantages of shorter external fixation time and overall cure time, a lower rate of complications, and better functional recovery of the limbs.

Antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap for one-stage treatment of chronic calcaneus osteomyelitis plus skin and soft tissue defects / 中华创伤骨科杂志

Objective:To investigate the clinical effects of antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap in the one-stage treatment of chronic calcaneus osteomyelitis plus skin and soft tissue defects.Methods:From January 2013 to September 2019, 48 patients were admitted to Department of Orthopedic Trauma, Xi'an Honghui Hospital Affiliated to Xi'an Jiaotong University for chronic calcaneal osteomyelitis complicated with skin and soft tissue defects. They were divided into 2 groups according to different bone grafts. In group A of 26 patients treated at one stage by antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap, there were 16 males and 10 females with an age of (45.0±11.7) years and an area of skin defect of (56.0±16.7) cm 2. In group B of 22 patients treated at one stage by simple autologous iliac bone combined with sural neurocutaneous flap, there were 13 males and 9 females with an age of (43.6±9.6) years and an area of skin defect of (53.8±16.2) cm 2. The volume of the ilium harvested, fracture healing time, infection control, donor site complications, pain score of visual analogue scale (VAS) and function recovery of the ankle were compared between the 2 groups. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for (15.3±6.0) months. Group A had a significantly smaller volume of the ilium harvested [(67.3±14.1) cm 3] than group B [(90.7±23.5) cm 3], a significantly lower rate of donor site complications [3.8% (1/26)] than group B [31.8% (7/22)], significantly lower VAS pain scores at 6, 12, 24, 48 and 72 hours than group B, and significantly lower WBC count, erythrocyte sedimentation rate and C-reactive protein at 2, 4, 8 weeks after operation than group B (all P<0.05). There was no statistically significant difference between the 2 groups in the infection control rate [96.2% (25/26) versus 77.3% (17/22)], the fracture healing time [(6.2±1.9) months versus (6.4±2.1) months], or the ankle-hindfoot score of AOFAS (The American Orthopaedic Foot and Ankle Society) (83.9±7.2 versus 82.5±8.7) at 6 months after operation (all P>0.05). Conclusion:In one-stage treatment of chronic calcaneal osteomyelitis complicated with skin and soft tissue defects, compared with simple autologous iliac bone combined with sural neurocutaneous flap, antibiotic-loaded calcium sulfate-autologous iliac bone combined with sural neurocutaneous flap can reduce the volume of the ilium harvested, pain score of VAS, and incidence of donor site complications, and improve the recovery of inflammatory indicators, leading to fine clinical effects.

Investigation report on an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province in 2021 / 中华地方病学杂志

Objective:To analyze the cause and epidemiological characteristics of an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province, and to provide scientific basis for anthrax prevention and control.Methods:Using on-site epidemiological investigation methods and the "Anthrax Epidemiological Case Investigation Form", case investigations were conducted based on the epidemiological contact history and close contacts of suspected anthrax cases reported by the national health care system ( n = 83). Scorched skin smears, diseased cattle tissues, soil samples from the slaughter site and smears from slaughter utensils were collected from cases for Real-time PCR testing and pathogenic bacteria isolation and culture, respectively. Anthrax determination criteria were carried out with reference to "Anthrax Diagnosis" (WS 283-2020). Results:A total of 13 cases of cutaneous anthrax were found in this outbreak, including 12 clinically diagnosed cases and one confirmed case (positive Real-time PCR test and isolation of a strain of Bacillus anthracis). The epidemiological investigation determined that the source of infection in this outbreak was diseased cattle, the transmission route was through slaughter of diseased cattle, contact with contaminated utensils and related cattle products, and the patients were mainly engaged in occupations related to cattle slaughter or cattle product collection and sale. A total of 84 samples were collected, including 13 skin scabs, 64 environmental samples and 7 beef samples. Thirty-six positive PCR tests were performed, with a positive rate of 42.86% (36/84). Among them, 100.00% (13/13) were positive for skin scab smear specimens, 29.69% (19/64) for environmental samples and 4/7 for beef samples. A total of 8 strains of Bacillus anthracis were isolated, including 6 environmental specimens, 1 suspected case and 1 beef strain, with an overall detection rate of 9.52% (8/84). Eighty-three close contacts were investigated. Thirteen households involved in the epidemic were disinfected by spraying (200 ml/m 2) with chlorine-containing disinfectant (5 000 mg/L), and a total of 40 households involved in the epidemic were disinfected, covering an area of about 10 765 m 2. Forty-five pieces of suspected contaminated clothing were burned and disposed of, and 152 pieces of kitchenware were soaked. Conclusions:Slaughter of infected cattle, contact with contaminated utensils and related cattle products are the main causes of this skin anthrax outbreak. Strengthening market supervision, deepening inter-animal epidemic prevention, carrying out publicity and education on anthrax prevention and control, and enhancing practitioners' awareness of disease prevention is the key to prevent anthrax from occurring.

Reaming after distal tibia cortical fenestration combined with antibiotic-loaded calcium sulphate for treatment of chronic tibial osteomyelitis after intramedullary nail fixation / 中华创伤骨科杂志

Objective:To compare the early clinical efficacy between reaming after distal tibia cortical fenestration combined with antibiotic-loaded calcium sulphate and trench grooving combined with polymethyl methacrylate (PMMA) for the treatment of chronic tibial osteomyelitis after intramedullary nail fixation.Methods:A retrospective analysis was conducted in the 20 patients who had been surgically treated for chronic tibial osteomyelitis after intramedullary nail fixation at Department of Trauma Orthopaedics, Honghui Hospital from January 2019 to January 2021. According to the surgical methods, they were divided into a reaming group and a grooving group. In the reaming group, there were 6 males and 3 females with an age of (47.6±11.4) years; in the grooving group, there were 9 males and 2 females with an age of (49.2±13.9) years. The 2 groups were compared in terms of duration of infection, operation time, intraoperative blood loss, bacterial culture results, total hospital stay, time for inflammatory indexes to return to normal, time for weight-bearing, complication rate, infection control rate, and good to excellent rate by Johner-Wruhs joint function scoring.Results:There was no significant difference in the preoperative general data between the 2 groups, showing they were comparable ( P > 0.05). All patients were followed up for 12 to 25 months after operation. There were no significant differences in the duration of infection, operation time, intraoperative blood loss, bacterial culture results, time for inflammatory indexes to return to normal, complication rate, infection control rate, or Johner-Wruhs scoring between the 2 groups ( P > 0.05). The total hospital stay [(11.7 ± 4.7) d] and weight-bearing time [(5.8 ± 1.6) weeks] for the reaming group were significantly shorter than those for the grooving group [(16.8 ± 4.6) d and (8.1 ± 2.9) weeks] ( P < 0.05). Conclusion:In the treatment of chronic tibial osteomyelitis after intramedullary nail fixation, compared with conventional trench grooving combined with PMMA, reaming after distal tibia cortical fenestration combined with antibiotic-loaded calcium sulphate can not only obtain satisfactory outcomes by infection control but also shorten the treatment cycle by allowing the patients to start early weight bearing.

Comparison of our modified hybrid bone transport technique and conventional bone transport technique in treatment of distal tibial osteomyelitis with bone defects involving the articular surface / 中华创伤骨科杂志

Objective:To introduce our modified hybrid bone transport technique using hindfoot arthrodesis nails combined with antibiotic-loaded calcium sulfate by comparison with conventional bone transport in the treatment of distal tibial osteomyelitis with bone defects involving the articular surface.Methods:The clinical data of 34 patients were retrospectively analyzed who had been treated at Department of Orthopaedics, Honghui Hospital for distal tibial osteomyelitis with bone defects involving the articular surface from September 2014 to September 2019. They were divided into 2 groups according to their way of repairing bone defects. In the modified group of 14 cases subjected to the treatment using the modified hybrid bone transport technique, there were 9 males and 5 females, with an age of (39.4±7.3) years. In the conventional group of 20 cases subjected to the treatment using conventional bone transport technique, there were 12 males and 8 females, with an age of (41.2±6.6) years. The external fixation time (EFT), external fixation index (EFI), self-rating anxiety scale (SAS) were recorded and compared between the 2 groups. Healing of bone defects and function were evaluated at the last follow-up according to the criteria of Association for the Study and Application of the Method of Ilizarov (ASAMI) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-posterior foot score, respectively. Complications were recorded according to the Paley classification.Results:There was no significant difference in the general data between the modified group and the conventional group, showing they were comparable ( P>0.05). Thirty-four patients were followed up for 18 to 32 months (average, 27 months) after operation. The modified group had significantly shorter EFT [(3.9±1.6) months] than the conventional group [(9.8±2.2) months], and significantly lower EFI [(0.48±0.09) months/cm] than the conventional group [(1.42±0.32) months/cm] ( P<0.05). The SAS [(48.1±4.7) points] in the modified group was significantly lower than that in the conventional group [(61.2±6.2) points], and the number of complications per capita in the former [(0.8±0.4)/case] was significantly smaller than that in the latter [(1.42±0.32)/case] ( P<0.05). There were no significan differences in the healing of bone defects or AOFSA ankle-posterior foot score ( P>0.05). In the modified group and the conventional group, respectively, 13 versus 12 patients were satisfied while 1 versus 8 patients unsatisfied, 1 versus 8 patients had grade-Ⅱ infection while 13 versus 12 patients did not, and 1 versus 9 patients had grade-Ⅲ infection while 13 versus 11 patients did not. There were significant differences between the 2 groups in the above indexes (all P<0.05). Conclusion:In the treatment of distal tibial osteomyelitis with bone defects involving the articular surface, compared with conventional bone transport technique, our modified hybrid bone transport technique using hindfoot arthrodesis nails combined with antibiotic-loaded calcium sulfate may lead to better clinical efficacy due to the advantages of shorter external fixation time, lower external fixation index and fewer complications.

Efficacy comparison of 3D printing technology-assisted and conventional open reduction and internal fixation for multiple rib fracture / 中华创伤杂志

Objective:To compare the efficacy of 3D printing technology-assisted and conventional open reduction and internal fixation of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 61 patients with multiple rib fracture admitted to Mindong Hospital Affiliated to Fujian Medical University and Fujian Provincial Hospital from July 2018 to March 2020. There were 44 males and 17 females, with age range of 18-73 years [(45.1±12.9)years]. Unilateral lung contusion and laceration occurred in 31 patients, while bilateral in 30. There were 19 patients accompanied by hempneumothorax and 16 by flail chest. Totally, 31 patients received 3D printing technology assisted open reduction and internal fixation (3D-assisted incision group) and 30 patients received conventional open reduction and internal fixation (conventional incision group). The incision length, operation time, intraoperative blood loss, postoperative 3-day visual analogue scale (VAS), duration of pain, indwelling time of chest tube, total length of hospital stay, postoperative bone callus formation time and rate of rib bone plate loosening were comapared in two groups. The short form 36 health survey (SF-36) score (ie, physical function, physical function, physical pain, general health, energy, social function, emotional function, mental health) preoperatively, at postoperative 6-month and at the last follow-up was compareted between two groups. Complications were observed at the same time.Results:All patients were followed up for 18-38 months [(26.4±5.5)months]. In 3D-assisted incision group, the incision length was (5.9±1.3)cm, with operation time for (84.6±7.8)minutes, intraoperative blood loss for (85.5±13.9)ml, postoperative 3-day VAS for (2.5±0.5)points, duration of pain for (5.9±0.7)days, indwelling time of chest tube for (3.4±0.7)days, total length of hospital stay for (7.0±1.0)days, postoperative callus formation time for (2.6±0.7)weeks and rate of rib bone plate loosening for 3.2%(1/31). By contrast, in conventional incision group, the incision length was (10.9±2.4)cm, with operation time for (127.1±12.5)minutes, intraoperative blood loss for (183.0±30.9)ml, postoperative 3-day VAS for (6.5±0.9)points, duration of pain for (11.2±1.8)days, indwelling time of chest tube for (7.8±0.8)days, total length of hospital stay for (15.1±1.2)days, postoperative callus formation time for (4.6±0.8)weeks and rate of rib bone plate loosening for 20.0%(6/30) ( P<0.05 or 0.01). There was no significant difference in preoperative SF-36 score between the two groups ( P>0.05). At 6 months after surgery, the subscores of SF-36 in 3D-assisted incision group were higher than those in conventional incision group except for "mental health" ( P<0.05 or 0.01). At the last follow-up, all the subscores of SF-36 in 3D-assisted incision group were higher than those in conventional incision group ( P<0.05 or 0.01). There were no obvious complications such as pulmonary infection or atelectasis. Conclusions:For multiple rib fracture, 3D printing technology-assisted open reduction and internal fixation is superior to conventional open reduction and internal fixation for it can shorten incision length, operation time, indwelling time of chest tube, total length of hospital stay and postoperative bone callus formation time, reduce intraoperative blood loss, relieve postoperative pain, reduce rate of rib bone plate loosening and improve quality of life of the patients.

Comparison of double mini locking plate and anatomical locking plate in the treatment of comminuted olecranon fracture / 国际外科学杂志

Objective:To compare the efficacy of double mini locking plate and anatomical locking plate in the treatment of comminuted olecranon fracture.Methods:The clinical data of 46 patients who underwent comminuted olecranon fracture in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from March 2017 to May 2020 were analyzed retrospectively. Among them, 21 cases were treated with double mini locking plate (double plate group) and 25 cases with anatomical locking plate (single plate group). The operation time, patient satisfaction, range of motion, return to work time, soft tissue stimulation to remove internal fixation, Mayo elbow performance score (MEPS), disabilities of arm, shoulder and hand score (DASH) of the two fixation methods were statistically compared. Measurement data with normal distribution were represented as ( ± s), and comparison between groups was conducted using the t test. Comparison between groups of count data was conducted using the chi-square test or Fisher exact probability. Results:All 46 patients were followed up for to (19.17±2.79) months. All fractures healed after operation. There was no significant difference in operation time, range of motion, patient satisfaction, MEPS and DASH scores among the two groups( P>0.05). The time of returning to work was (8.47±2.13) weeks in the double plate group and (9.78±1.98) weeks in the single plate group, and the difference was statistically significant ( P< 0.05). There were 9 cases of internal fixation due to soft tissue stimulation, 1 cases in double plate group and 8 cases in single plate group, and the difference was statistically significant ( P<0.05). Conclusions:Compared with anatomical locking plate, the treatment of olecranon fracture with double mini locking plate can effectively reduce soft tissue stimulation and promote patients to return to work early, and the operation time is not significantly prolonged, and the biomechanical advantage is obvious, the clinical effect is satisfactory and the postoperative function is good, so it is an effective treatment.