Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study / 中国结合医学杂志

OBJECTIVE@#To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application.@*METHODS@#Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events.@*RESULTS@#Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days.@*CONCLUSIONS@#Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

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

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

Progress in Research and Application of CAR-T Cell Therapy in T-Lymphocyte Tumors --Review / 中国实验血液学杂志

T-lymphocyte tumors are a group of diseases containing various types of lymphatic system tumors, with strong heterogeneity and poor clinical outcomes. Chimeric antigen receptor T (CAR-T) cell therapy, as a new immune cell therapy, has made a breakthrough in the field of B-lymphocyte tumors. People are interested in the application prospect of this technique in the field of T-lymphocyte tumors. Some studies have shown that CAR-T cell therapy has made some progress in the treatment of T-lymphocyte tumors, and CAR-T for some targets has entered the stage of clinical trials. However, due to the characteristics of T cells, there are also many challenges. This article reviews the research and application of CAR-T cell therapy in T-lymphocyte tumors.

Investigation of Antigen and Gene Frequency of Kell(K) and Rh(D) Blood Groups in Xinjiang / 中国实验血液学杂志

OBJECTIVE@#To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area.@*METHODS@#A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed.@*RESULTS@#The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01).@*CONCLUSION@#The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.

Effect of Circulating Plasma Cells on the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#to analyze the effect of circulating plasma cells(CPC) on the prognosis of patients with multiple myeloma(MM) in the era of new drugs, and to explore the new definition standard of primary plasma cell leukemia(pPCL).@*METHODS@#The clinical data of 321 patients with newly diagnosed MM and 21 patients with pPCL admitted to our hospital from January 2014 to May 2022 were retrospectively analyzed. According to the proportion of CPC in peripheral blood smears, all patients were divided into 4 groups: CPC 0% group(211 cases), CPC 1%-4% group(69 cases), CPC 5%-19% group(41 cases) and CPC≥20% group(21 cases). The clinical features of patients in each group were compared and the prognosis fators was analyzed.@*RESULTS@#The median OS of the four groups were 44.5,21.3,24.6 and 12.8 months, respectively. Among them, 295 patients(86.3%) were treated with new drugs, and the median OS of the four groups were not reached, 26.7, 24.6 and 14.9 months, respectively. As the survival curves of CPC 5%-19% group and CPC≥20% group were similar, the patients were divided into CPC<5% group and CPC≥5% group, the median OS of CPC<5% group was better than that in CPC≥5% (43.5 vs 22.3 months, P<0.001). In addition, the median OS of patients in the CPC 1%-4% group was also significantly lower than that in the CPC 0% group and similar to that in the CPC≥5% group. Multivariate analysis showed that 1%-4% CPC was an independent risk factor for the OS of patients with CPC<5%. The patients with CPC<5% were stratified by R-ISS staging, and the OS of R-ISS stage Ⅰ or stage Ⅱ with 1%-4% CPC was similar to that of R-ISS stage Ⅲ. The newly defined pPCL patients showed increased tumor load and obvious invasive characteristics. Multivariate analysis showed no independent prognostic factors for pPCL, and high-risk cytogenetic abnormalities(HRCA) had no significant effect on the prognosis.@*CONCLUSION@#The validity of IMWG's new pPCL definition standard was verified, and it was found that the survival of MM with 1%-4% CPC also is poor and the prognosis is very close to pPCL. In addition, the newly defined pPCL has unique clinical and biological characteristics.

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Research Progress and Application of Daratumumab in Non-Multiple Myeloma--Review / 中国实验血液学杂志

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.

Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.@*RESULTS@#APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.@*CONCLUSION@#The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.

Efficacy and Safety of Flumatinib in Treatment of Patients with Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the efficacy and safety of flumatinib in the treatment of patients with chronic myeloid leukemia (CML).@*METHODS@#The clinical data of 56 CML patients treated with flumatinib from January 2020 to December 2021 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. Patients were divided into three groups: 35 new diagnosed CML patients treated with flumatinib (group A), 10 patients with imatinib/dasatinib intolerance (group B) and 11 patients with imatinib/dasatinib resistance (group C) switched to flumatinib treatment, respectively. The molecular response and adverse effects of flumatinib treatment were evaluated.@*RESULTS@#In group A, the early molecular response (EMR) at 3 months was 40.0%, and the major molecular response (MMR) at 6 and 12 months was 43.7% and 46.2%, respectively. In group B, the EMR was 50.0% at 3 months, and the MMR was 70.0% and 66.2% at 6 and 12 months, respectively. Among evaluable patients, 6 cases in group B achieved molecular response of 4.5 (MR4.5) at 12 months after switching to flumatinib treatment. In group C, 3 cases who switched from imatinib resistance to flumatinib achieved MR4.5 at 12 months, but 2 cases who switched from dasatinib resistance to flumatinib failed. Subgroup analysis showed significant differences in EUTOS long-term survival (ELTS) scores for patients in the medium-risk/high-risk group compared with those in the low-risk group for 3-month EMR (18.8% vs 57.9%), 6-month MMR (15.4% vs 63.2%) and 12-month MR4.5 (15.4% vs 69.2%) (P =0.036, P =0.012,P =0.015). The most common adverse effect in group A was thrombocytopenia, accounting for 54.5%, and 22.8% (8/35) patients discontinued the drug due to haematological adverse effects. Compared with patients who did not discontinue the drug or whose recovery time from discontinuation due to haematological toxicity was <1 month, patients whose recovery time from discontinuation was ≥1 month had a significantly worse 3-month EMR, 6-month MMR and 12-month MR4.5 (P =0.028, P =0.021, P =0.002).@*CONCLUSIONS@#Flumatinib has better molecular response and tolerance in patients with primary, imatinib/dasatinib-intolerant or resistant CML. Medium-risk/high-risk in ELTS score and time to recovery from discontinuation due to haematological toxicity ≥1 month are important factors influencing achievement of better molecular response in flumatinib treatment.

Application of femoral I.D.E.A.L localization in anterior cruciate ligament reconstruction with single bundle anterior cruciate ligament / 中国骨伤

OBJECTIVE@#To evaluate the effect of femoral I.D.E.A.L localization in single bundle anterior cruciate ligament reconstruction (ACLR).@*METHODS@#From January 2019 to October 2022, 122 patients with anterior cruciate ligament injury were treated with ACLR, including 83 males and 39 females. The age ranged from 23 to 43 years old, with an average of (32.19 ±8.55) years old. The course of disease ranged from 1 week to 6 months. According to the different surgical schemes, the patients were divided into two groups, namely the traditional group, which adopted the over-the-top femoral lateral positioning scheme, including 64 patients. The I.D.E.A.L group adopted the I.D.E.A.L femoral lateral positioning scheme, including 58 patients. The patient has pain and dysfunction of knee joint before operation. MRI of knee joint indicates anterior cruciate ligament injury. The visual analogue scale(VAS), International Knee Documentation Committee(IKDC) scoring system and Lysholm scoring system were used to evaluate the knee joint function of the patient. KT-2000 was used to detect the recovery of knee joint after operation and to count the postoperative complications.@*RESULTS@#The wounds healed well after operation. One hundred and twenty-tow patients were followed up for 15 to 46 months, with an average of (25.45±9.22) months. The knee joint stability of patients after operation was significantly increased. The VAS at 1 day and 1 week after operation of patients in the I.D.E.A.L group was significantly lower than that in the traditional group(P<0.05). The IKDC score and Lysholm score of patients in the I.D.E.A.L group were significantly higher than those in the traditional group(P<0.05). In the traditional group, there were 6 cases of short-term (<1 month) complications and 19 cases of long-term (≥1 month)complicatios. In the I.D.E.A.L group, there were 3 cases of short-term complications and 7cases of long-term complications(P<0.05).@*CONCLUSION@#The single bundle anterior cruciate ligament reconstruction and femoral I.D.E.A.L positioning can achieve better early postoperative effect and reduce early postoperative pain.

Experimental study on high-frequency subharmonic scattering characteristics of ultrasound contrast agent microbubbles under low ambient pressure / 生物医学工程学杂志

Correlation between nonlinear subharmonic scattering of ultrasound contrast agent microbubbles and ambient pressure is expected to be used for local brain tissue pressure monitoring. Although high-frequency ultrasound has achieved high-resolution imaging of intracranial microvessels, the research on high-frequency subharmonic scattering characteristics of microbubbles is insufficient at present, which restricts the research progress of estimating local brain tissue pressure based on high-frequency subharmonic scattering of microbubbles. Therefore, under the excitation of 10 MHz high-frequency ultrasound, the effects of different acoustic pressures and ambient pressures on the high-frequency subharmonic scattering characteristics of three different ultrasound contrast agents including SonoVue, Sonazoid and Huashengxian were investigated in this in vitro study. Results showed that the subharmonic scattering amplitudes of the three microbubbles increased with the increase of ambient pressure at the peak negative acoustic pressures of 696, 766 and 817 kPa, and there was a favorable linear correlation between subharmonic amplitude and ambient pressure. Under the above three acoustic pressures, the highest correlation coefficient of SonoVue was 0.948 ( P = 0.03), the highest sensitivity of pressure measurement was 0.248 dB/mm Hg and the minimum root mean square error (RMSE) was 2.64 mm Hg. Sonazoid's highest correlation coefficient was 0.982 ( P < 0.01), the highest sensitivity of pressure measurement was 0.052 dB/mm Hg and the minimum RMSE was 1.51 mm Hg. The highest correlation coefficient of Huashengxian was 0.969 ( P = 0.02), the highest sensitivity of pressure measurement was 0.098 dB/mm Hg and the minimum RMSE was 2.00 mm Hg. The above in vitro experimental results indicate that by selecting ultrasound contrast agent microbubbles and optimizing acoustic pressure, the correlation between high-frequency subharmonic scattering of microbubbles and ambient pressure can be improved, the sensitivity of pressure measurement can be upgraded, and the measurement error can be reduced to meet the clinical demand for local brain tissue pressure measurement, which provided an important experimental basis for subsequent research in vivo.

Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection / 中国中药杂志

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Research Progress of Allogeneic Hematopoietic Stem Sell Trans-plantation in the Treatment of Adult Hemophagocytic Lympho-histiocytosis --Review / 中国实验血液学杂志

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.

Applicability of Seven Glomerular Filtration Rate Evaluation Formulas in Dose Adjustment of High Concentration of Methotrexate Chemotherapy in Children with ALL / 中国实验血液学杂志

OBJECTIVE@#To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPIscysc, Cockrofi-Gault, CKD-EPIScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary.@*RESULTS@#All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPIscysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05).@*CONCLUSION@#Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPIscysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.

Biomechanical analysis of four internal fixations for Pauwels Ⅲ femoral neck fractures with defects / 中国骨伤

OBJECTIVE@#To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture.@*METHODS@#Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared.@*RESULTS@#When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS.@*CONCLUSION@#For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Characteristics of plasma Epstein-Barr virus DNA in children with primary infection / 中华儿科杂志

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.