Rapid detection and genotyping of SARS-CoV-2 Omicron BA.4/5 variants using a RT-PCR and CRISPR-Cas12a-based assay / 南方医科大学学报

OBJECTIVE@#To establish a rapid detection and genotyping method for SARS-CoV-2 Omicron BA.4/5 variants using CRISPPR-Cas12a gene editing technology.@*METHODS@#We combined reverse transcription-polymerase chain reaction (RT-PCR) and CRISPR gene editing technology and designed a specific CRISPPR RNA (crRNA) with suboptimal protospacer adjacent motifs (PAM) for rapid detection and genotyping of SARS- CoV-2 Omicron BA.4/5 variants. The performance of this RT- PCR/ CRISPPR-Cas12a assay was evaluated using 43 clinical samples of patients infected by wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Omicron BA. 1 and BA. 4/5 variants and 20 SARS- CoV- 2-negative clinical samples infected with 11 respiratory pathogens. With Sanger sequencing method as the gold standard, the specificity, sensitivity, concordance (Kappa) and area under the ROC curve (AUC) of RT-PCR/CRISPPR-Cas12a assay were calculated.@*RESULTS@#This assay was capable of rapid and specific detection of SARS- CoV-2 Omicron BA.4/5 variant within 30 min with the lowest detection limit of 10 copies/μL, and no cross-reaction was observed in SARS-CoV-2-negative clinical samples infected with 11 common respiratory pathogens. The two Omicron BA.4/5 specific crRNAs (crRNA-1 and crRNA-2) allowed the assay to accurately distinguish Omicron BA.4/5 from BA.1 sublineage and other major SARS-CoV-2 variants of concern. For detection of SARS-CoV-2 Omicron BA.4/5 variants, the sensitivity of the established assay using crRNA-1 and crRNA-2 was 97.83% and 100% with specificity of 100% and AUC of 0.998 and 1.000, respectively, and their concordance rate with Sanger sequencing method was 92.83% and 96.41%, respectively.@*CONCLUSION@#By combining RT-PCR and CRISPPR-Cas12a gene editing technology, we successfully developed a new method for rapid detection and identification of SARS-CoV-2 Omicron BA.4/5 variants with a high sensitivity, specificity and reproducibility, which allows rapid detection and genotyping of SARS- CoV-2 variants and monitoring of the emerging variants and their dissemination.

Clinical features and treatment status of adolescent patients with bipolar disorder / 四川精神卫生

BackgroundGender and age differences in the clinical manifestations of patients with bipolar disorder can affect the clinical diagnosis and treatment process. The current treatment effect of bipolar disorder in adolescents is not ideal， which has become the main reason for disability during the learning period. ObjectiveTo analyze the clinical features and medication therapy status of bipolar disorder in adolescents， and to provide references to support for personalized diagnosis and treatment. MethodsOn January 16， 2023， 1 169 patients with bipolar disorder who were hospitalized at Beijing Anding Hospital Affiliated Capital Medical University from January 1， 2014 to December 31， 2017 were retrospectively enrolled. Medical records were collected and analyzed to compare the clinical features among patients of different gender and age groups， and to explore the differences in medication use among patients of different genders in different types of seizures. ResultsMale patients reported a larger proportion of manic episodes， and a smaller proportion of depressive episodes than female patients （P<0.05）.Female patients reported a larger proportion of non-suicidal self-harm behaviors than male patients （χ2=7.761， P<0.01）.And patients in low-age group featured a larger proportion of mixed seizures， impulsive behaviors and family history of bipolar disorders along with a smaller proportion of manic episodes than those in high-age group （P<0.05 or 0.01）. High-age group had a longer average length of hospital stay than low-age group （t=-2.930， P<0.01）. In manic episode patients， males were found to have a larger proportion of valproate and atypical antipsychotic drug administration than females （P<0.01）. Among atypical antipsychotic drugs， males accounted for a larger proportion of administration of risperidone and olanzapine （χ2=26.957） than females （P<0.05 or 0.01）， while females constituted a larger proportion of administration of quetiapine （χ2=14.865） and aripiprazole than males （P<0.01）. In depressive episode patients， females had a larger proportion of administration of olanzapine than males （P<0.01）. In patients with mixed seizures， females occupied a larger proportion of administration of lithium carbonate than males （χ2=9.253， P<0.01）， and males exhibited a larger proportion of administration of valproate than females （P<0.05）. ConclusionDifferences have been shown in diagnostic classification and concomitant symptoms among adolescent bipolar disorder of different genders and ages. Furthermore， medications of lithium carbonate， valproate， atypical antipsychotic and other drugs differ by gender among adolescents of different subtypes of bipolar disorder. ［Funded by Key Special Project of the National Key R&D Program of the Ministry of Science and Technology for "Major Chronic Non communicable Disease Prevention and Control Research" （number， 2017YFC1311101）］

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Advances in the treatment of hypertrophic cardiomyopathy with cardiac myosin inhibitors / 中国药房

In recent years， with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy， novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin， thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient， the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers， and improve New York Heart Association （NYHA） cardiac function class. They are safe， have mild adverse reactions， and can be tolerated by patients. Compared to Mavacamten， Aficamten， as a structurally optimized product， has a shorter half-life and fewer drug-drug interactions， which is more conducive to drug- targeted dose titration.

Predictive value of vascular endothelial growth factor expression and microvascular density for the depth of infiltration in early gastric cancer / 肿瘤研究与临床

Objective:To investigate the predictive value of vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) for the depth of infiltration in early gastric cancer.Methods:The pathological tissues of 24 patients with early gastric cancer (early gastric cancer group), 23 patients with advanced gastric cancer (advanced gastric cancer group) and 10 patients with gastritis (gastritis group) who admitted to Fenyang Hospital Affiliated of Shanxi Medical University from January 2020 to January 2022 were retrospectively collected. Immunohistochemistry was used to detect VEGF expression and MVD in the lesion tissues of each group, and the correlation of VEGF expression and MVD in gastric cancer tissues with the clinicopathological characteristics of patients was analyzed. Postoperative pathological diagnosis was treated as the gold standard. The efficacy of VEGF and MVD in predicting the depth of infiltration in gastric cancer and early gastric cancer was assessed by using the receiver operating characteristic (ROC) curve.Results:The VEGF positive expression rate was 10.00% (1/10), 29.17% (7/24) and 78.26% (18/23) in gastritis group, early gastric cancer group and advanced gastric cancer group, respectively, and the MVD was (21±5) strips/field, (23±9) strips/field and (43±15) strips/field, respectively. The positive expression rate of VEGF and MVD were related with the tumor diameter [>2 cm vs. ≤2 cm:69.70% (23/33) vs. 14.29% (2/14), (39±15) strips/field vs. (20±8) strips/field] and infiltration depth of gastric cancer [intramucosal carcinoma vs. submucosal carcinoma vs. advanced gastric cancer: 26.31% (5/19) vs. 40.00% (2/5) vs. 78.26% (18/23), (20±7) strips/field vs. (36±3) strips/field vs. (43±15) strips/field] (all P > 0.01), while not related with gender, age, tumor location, differentiation degree (all P > 0.05). The ROC curve analysis showed that the area under the curve (AUC) of VEGF and MVD in predicting the depth of infiltration in gastric cancer was 0.716 (95% CI 0.581-0.828) and 0.711 (95% CI 0.573-0.823), respectively; the optimal cut-off value of VEGF and MVD was positive and 24.8 strips/field, with the sensitivity of 53.19%, 61.70%, and the specificity of 90.00% both. The AUC of VEGF and MVD in predicting the depth of infiltration in early gastric cancer was 0.596 (95% CI 0.414-0.760) and 0.506 (95% CI 0.330-0.681) , respectively; the optimal cut-off value of VEGF and MVD was positive and 32.5 strips/field, with the sensitivity of 29.17% , 70.83%, and the specificity of 90.00%, 0, respectively. Conclusions:VEGF expression and MVD are elevated with the increase of depth of gastric cancer infiltration, while the value of the combination of both in predicting the depth of infiltration in early gastric cancer is not high.

Changes in CD100 expression and its regulatory effect on CD8 + T cell function in peripheral blood of patients with herpes zoster / 中华皮肤科杂志

Objective:To investigate changes in expression of plasma soluble CD100 (sCD100) and membrane-bound CD100 (mCD100) on peripheral T cells in patients with herpes zoster, and to observe the regulatory effect of exogenous CD100 on CD8 + T cells. Methods:A total of 53 patients with herpes zoster attending the Zhumadian Central Hospital from July 2019 to April 2021 were enrolled, so were 25 age- and sex-matched healthy controls. Anticoagulated venous blood samples were collected, plasma and peripheral blood mononuclear cells were isolated, plasma sCD100 levels were detected by enzyme-linked immunosorbent assay, and mCD100 expression on CD4 + and CD8 + T cells was determined by flow cytometry. After the purification of CD8 + T cells, the secretion levels of cytotoxic molecules and cytokines by CD8 + T cells were measured and compared between herpes zoster patients and controls. Some purified CD8 + T cells from herpes zoster patients were stimulated with recombinant human CD100 and recombinant varicella-zoster virus glycoprotein, and the effect of recombinant human CD100 on the secretion of cytotoxic molecules and cytokines by CD8 + T cells was investigated. Comparisons between groups were conducted by t test. Results:Plasma sCD100 levels were significantly lower in the herpes zoster group (1.12 ± 0.23 ng/ml) than in the control group (1.31 ± 0.28 ng/ml, t = 2.97, P = 0.004), the proportion of mCD100 + CD8 + T cells was significantly higher in the herpes zoster group (17.41% ± 4.26%) than in the control group (14.69% ± 3.70%, t = 2.52, P = 0.014), and no significant difference in the proportion of mCD100 + CD4 + T cells was found between the two groups (2.52% ± 0.58% vs. 2.32% ± 0.56%, t = 1.27, P = 0.208). The herpes zoster group showed significantly decreased mRNA expression of perforin and granzyme B in, and lower secretion levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α by CD8 + T cells compared with the control group (all P < 0.05). After stimulation with recombinant human CD100, levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α in the culture supernatant of CD8 + T cells (43.68 ± 14.12, 126.8 ± 22.92, 12.79 ± 3.66, 310.0 ± 79.90 pg/ml, respectively ) were significantly higher than those in non-stimulated group (34.55 ± 10.78, 99.04 ± 10.44, 9.53 ± 2.00, 275.6 ± 68.04 pg/ml, respectively, all P < 0.05) . Conclusion:There was an imbalance between sCD100 and mCD100 expression in patients with herpes zoster, and exogenous sCD100 may enhance the cytotoxicity of CD8 + T cells in herpes zoster patients.

Comparison of the therapeutic effects of different antibacterial drugs combined in the treatment of adult brucellosis patients / 中华地方病学杂志

Objective:To compare the efficacy of different antibacterial drugs combined in the treatment of adult brucellosis patients.Methods:Using a prospective design, 60 adult brucellosis patients admitted to the Affiliated Hospital of Jining Medical University from January 2018 to December 2021 were selected as the study subjects. They were randomly divided into an observation group ( n = 30) and a control group ( n = 30) using a random number table method. The observation group was treated with rifampicin combined with minocycline, and the control group was given rifampicin combined with doxycycline. The course of treatment in both groups was 6 weeks. The efficacy and clinical symptom disappearance time between the two groups, as well as the blood white blood cell count (WBC), alanine aminotransferase (ALT) levels, and serum interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels before and after treatment, and the occurrence of adverse reactions were compared. Results:The total effective rate of the observation group (96.67%, 29/30) was higher than that of the control group (73.33%, 22/30), with a statistically significant difference (χ 2 = 4.71, P = 0.030). The disappearance time of joint pain, hyperhidrosis, gastrointestinal reactions, and fever in the observation group were shorter than those in the control group, and the differences were statistically significant ( P < 0.05). After treatment, the blood WBC and ALT levels in both groups decreased compared to before treatment ( P < 0.05). After treatment, the blood WBC and ALT levels in the observation group were lower than those in the control group ( P < 0.001). The levels of serum IFN-γ and IL-10 were both decreased after treatment compared to before treatment in two groups, while IL-4 level increased compared to before treatment ( P < 0.05). The levels of serum IFN-γ and IL-10 in the observation group were lower than those of the control group, while IL-4 level was higher than that of the control group ( P < 0.001). The incidence of adverse reactions in the observation group (13.33%, 4/30) was lower than that in the control group (36.67%, 11/30), and the difference was statistically significant (χ 2 = 4.36, P = 0.037). Conclusion:The combination of rifampicin and minocycline in the treatment of adult brucellosis patients has good efficacy and can reduce serum IFN-γ and IL-10 levels and increase IL-4 level with few adverse reactions.

Application of video laryngoscope combined with bronchial blocker and double-lumen tube in the standardized training of anesthesia for tracheal intubation / 中华医学教育探索杂志

Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.

Correlation analysis of plasma microRNA-122 and microRNA-33a with severity of coronary artery disease in patients with type 2 diabetes mellitus and coronary heart disease / 中国医师进修杂志

Objective:To investigate the correlation between plasma microRNA (miR)-122, miR-33a and the severity of coronary artery disease in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease.Methods:The clinical data of 196 patients with T2DM from January 2019 to October 2021 in Xuzhou First People′s Hospital were retrospectively analyzed. Among them, 81 cases were complicated with coronary heart disease (combined group), 115 cases were not complicated with coronary heart disease (control group). The plasma levels of miR-122 and miR-33a were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the plasma level of N-terminal B-type natriuretic peptide precursor (NT-proBNP) was detected by enzyme-linked immunosorbent assay. In combined group, the number of coronary artery lesions was determined according to the results of coronary angiography, and Gensini score was evaluated. Linear regression model was used to analyze the relationship between plasma miR-122, miR-33a and NT-proBNP levels with the incidence of coronary heart disease in patients with T2DM. Receiver operating characteristic (ROC) curve was used to analyze the plasma miR-122 and miR-33a in predicting efficiency of coronary heart disease in patients with T2DM. In combined group, Spearman correlation method was used to analyze the relationship between plasma miR-122, miR-33a and the number of coronary artery lesions, and Pearson correlation method was used to analyze the relationship between plasma miR-122, miR-33a and plasma NT proBNP, Gensini score.Results:The plasma miR-122, miR-33a and NT-proBNP in combined group were significantly higher than those in control group: 5.76 ± 1.35 vs. 1.18 ± 0.33, 1.39 ± 0.37 vs. 0.65 ± 0.11 and (786.87 ± 156.39) ng/L vs. (103.45 ± 19.27) ng/L respectively, and there were statistical differences ( P<0.01). Linear regression result showed that plasma miR-122, miR-33a, and NT-proBNP were positive correlation with occurrence of coronary heart disease in patients with T2DM ( P<0.01); ROC curve analysis result showed that the area under curve of plasma miR-122, miR-33a and combination in predicting coronary heart disease in patients with T2DM were 0.816, 0.845 and 0.912 respectively (95% CI 0.744 to 0.865, 0.768 to 0.892 and 0.836 to 0.967). Coronary angiography result showed that there were 46 cases of single vessel lesions, 25 cases of double vessel lesions and 10 cases of three vessel lesions. The plasma miR-122, miR-33a, NT-proBNP and Gensini score in patients with three vessel lesions were significantly higher than those in patients with double vessel lesions and patients with single vessel lesions: 6.52 ± 0.96 vs. 4.95 ± 0.85 and 3.74 ± 0.52, 1.45 ± 0.31 vs. 1.06 ± 0.25 and 0.81 ± 0.13, (829.78 ± 62.59) ng/L vs. (627.48 ± 47.12) and (502.64 ± 38.24) ng/L, (63.89 ± 12.71) scores vs. (42.18 ± 6.03) and (22.36 ± 2.41) scores, the indexes in patients with double vessel lesions were significantly higher than those in patients with single vessel lesions, and there were statistical differences ( P<0.05). In combined group, Spearman correlation analysis result showed that the plasma miR-122 and miR-33a were positive correlation with the number of coronary artery lesions ( r = 0.879 and 0.825, P<0.05); Pearson correlation analysis result showed that the plasma miR-122 and miR-33a were positive correlation with the plasma NT-proBNP and Gensini score (miR-122: r = 0.896 and 0.788, miR-33a: r = 0.871 and 0.765; P<0.05). Conclusions:The plasma levels of miR-122 and miR-33a are related to the occurrence of coronary heart disease and severity of coronary artery disease in patients with T2DM, which may be used to guide the prevention and treatment of coronary heart disease in patients with T2DM.

Research progress of mesh-related visceral complications after tension-free inguinal hernia repair / 中华消化外科杂志

Mesh-related visceral complications caused by mesh erosion after tension-free inguinal hernia repair are one kind of rare long-term complications, but they are easily neglected. Interval time from initial hernia repair to mesh-related visceral complications by preperitoneal and laparoscopic repair is short. Rutkow and transabdominal preperitoneal repair have the highest reported rate. Lichtenstein has the longest interval time and the lowest reported rate. The most frequently eroded organs are sigmoid colon, bladder and small intestine. The common clinical manifestations of sigmoid colon erosion are hematochezia, abdominal wall fistula and colitis, hematuria and recurrent urinary tract infection in bladder erosion cases, intestinal obstruction and abdominal wall fistula in intestinal erosion case, sigmoid-bladder fistula and intestinal-bladder fistula in multiple organ erosion cases. Resection or repair of corresponding organs with mesh removal have good efficacies in most patients. The authors summarize and analyze researches on mesh-related visceral complications after tension-free inguinal hernia repair from 1994 to 2021, review their advances, in order to raise awareness of such complications in clinicians.

Effect study of guideline-based care bundles on the prevention of enteral nutrition-related diarrhea in ICU patients / 中国实用护理杂志

Objective:To construct the evidence-based care bundles for enteral nutrition-related diarrhea in ICU patients and evaluate its effectiveness.Methods:Evidence-based care bundles for enteral nutrition-related diarrhea in ICU patients were constructed according to the best evidence from 5 guidelines. 12 best evidences were summarized, and 12 cluster schemes for diarrhea management were constructed. 175 patients admitted to ICU of Shandong Provincial Hospital Affiliated to Shandong First Medical University from June to December 2020 were selected as the pre implementation group which was given enteral nutrition nursing according to routine nursing measures, and 186 patients admitted to ICU from March to October 2021 were selected as the post implementation group which received nrusing care with evidence-based cluster schemes. The rate of diarrhea in ICU patients undergoing enteral nutrition support before and after using best evidence was compared, and awareness of best evidence among nurses before and after training, and implementation of various measures by nurses after the plan were also compared.Results:After the care bundles were applied, the incidence of diarrhea decreased from 26.29% (46/175) to 11.83% (22/186) with statistically significant difference ( χ2=12.33, P<0.05). The diarrhea knowledge score was improved from 52-100 (75.79 ± 10.18) points to 72-100 (90.00 ± 6.71) points and had a significant difference ( t=-8.88, P<0.05). After the care bundles were applied, the rate of ICU nurses′ diarrhea identification and evaluation, analysis of influencing factors of enteral nutrition associated diarrhea, nasal feeding, selection of enteral nutrition formula and drug were 94.83% (55/58), 91.38% (53/58), 100.00 (58/58), 93.10% (54/58), 94.83% (55/58),significantly improved than 68.97% (40/58), 63.79% (37/58), 81.03% (47/58), 62.07% (36/58), 70.69% (41/58) before applied ( χ2 values were 8.66-14.33, all P<0.01). The implementation rate after the plan was more than 95.00%. Conclusions:The application of the evidence-based care bundles can effectively reduce the incidence of enteral nutrition diarrhea in ICU patients, improve nursing practice and the quality of care.

Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

Meta-analysis for the effects of problem solving therapy on the elderly patients with depression / 中国实用护理杂志

Objective:To evaluate the clinical effects of problem solving therapy on the elderly patients with depression by Meta-analysis.Methods:Randomized controlled trials articles regarding the effects of problem solving therapy on the elderly patients with depression were searched from the database of PubMed, EMbase, Medline, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Database and Wanfang Data electronically. SMD was used as the post merger response, and its 95% CI was calculated. Results:Ten articles were recruited and a total of 1 005 patients were included, 501 patients in the intervention group and 504 patients in the control group. Meta-analysis showed that problem solving therapy was significantly better than the control group in the treatment of depressive symptoms in the elderly patients with depression ( SMD =-0.64, 95% CI -0.98 - -0.31, P<0.05); during the follow-up within 3 months and 6 months after the intervention, the improvement of depression in the intervention group was better than that in the control group ( SMD=-0.62, 95% CI -1.00 - -0.25, P<0.05) and ( SMD =-0.79, 95% CI -1.03 - -0.55, P<0.05), respectively. Compared with the control group, the intervention group had an effect on the improvement of dysfunction ( SMD=-1.28, 95% CI -2.22 - -0.35, P<0.05). Conclusions:Problem solving therapy can improve the depressive symptoms of the elderly patients with depression and the clinical effect remains stable for a certain period of time; problem solving therapy has an improvement effect on the dysfunction of the elderly patients with depression.

Regulation of Wnt/β-catenin Signaling Pathway in Renal Interstitial Fibrosis by Traditional Chinese Medicine：A Review / 中国实验方剂学杂志

Chronic kidney disease （CKD） has become a public health problem worldwide with renal interstitial fibrosis （RIF） serving as the important pathological feature and pathological outcome of various CKD. Therefore， anti-fibrosis therapy has important practical significance for delaying the progression of CKD and improving the prognosis of CKD patients. The Wnt/β-catenin signaling pathway is a conserved signaling pathway through evolution， which plays a vital role in organ formation， tissue homeostasis， and disease progression during embryonic development. A growing body of research has confirmed that the Wnt/β-catenin signaling pathway is one of the key signaling pathways in a variety of kidney diseases and its activation is closely related to RIF. RIF is aggravated by the specific regulation of the expression of downstream target genes， such as fibroblasts， zinc finger transcription factor 1 （Snail1）， M2 macrophages， matrix metalloproteinase-7 （MMP-7）， plasminogen activator inhibitor-1 （PAI-1）， and renin-angiotensin system（RAS）， and relieved by targeting the signaling pathways， such as Klotho， Dickkopf-related protein 1 （DKK1）， secreted frizzled-related protein 1 （Sfrp1）， and indocyanine green-001. In addition，the pathological view of RIF in traditional Chinese medicine （TCM） coincides with that in western medicine. Based on the etiology and pathogenesis of TCM in the combination of deficiency and excess， TCM regulates fibrosis-promoting mediators by tonifying deficiency， eliminating turbidity， removing the toxin， resolving stasis， and treating both symptoms and root causes in a multi-target， multi-layer， and multi-pathway manner to inhibit the Wnt/β-catenin signaling pathway and play an important role in renal protection. Therefore， this study reviewed the regulatory mechanism of the Wnt/β-catenin signaling pathway in RIF and the protective effect of targeting this signaling pathway on renal function and discussed the potential role of TCM in delaying the progression of RIF， which is expected to provide new targets and strategies for the prevention and treatment of RIF.

Regulatory Effect of Quyu Huatan Tongmai Prescription on Intestinal Microflora in Golden Hamster with Hyperlipidemia / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg-1）， Huatan group （0.39 g·kg-1）， Jiedu group （0.07 g·kg-1）， and prescription group （1.42 g·kg-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

Structural design of an ankle multi-dimensional rehabilitation training device / 中国康复理论与实践

@#Objective To design a novel ankle rehabilitation trainer to meet the rehabilitation needs of multiple motion after ankle injury.Methods Based on the model of ankle motion, combined with the mechanical design and the rehabilitation techniques, a trainer was designed using SolidWorks software, including rotational plane and dynamic mechanism design, allowing a multi-dimensional motion.Results The trainer completed the motion of plantar-flexion/dorsiflexion, inversion/eversion, and adduction/abduction of ankle, to carry out uniaxial or multidimensional motor rehabilitation.Conclusion The mechanical structure of the rehabilitation trainer is simple, meeting the needs of ankle rehabilitation training program, which can be used to relieve ankle joint motor dysfunction.