Pathogenesis of Airway Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.

Analysis of anxiety and depressive status and influencing factors in patients with colorectal polyps in part of Xinjiang area / 中华消化杂志

Objective:To investigated the prevalence of anxiety and depression symptoms in patients with colorectal polyps in part of Xinjiang area and to explore the associated influencing factors related to psychological status, and to provide evidence and clues to promote the diagnosis and treatment of psychosomatic diseases in digestive system.Methods:From December 2021 to June 2022, at the First Affiliated Hospital of Shihezi University, the Fourth Division Hospital of Xinjiang Production and Construction Corps, the Third Division Hospital of Xinjiang Production and Construction Corps (Kashgar Hospital), the Thirteenth Division Red Star Hospital of Xinjiang Production and Construction Corps, the Tenth Division Beitun Hospital of Xinjiang Production and Construction Corps, the Seventh Division Hospital of Xinjiang Production and Construction Corps, the Fifth Division Hospital of Xinjiang Production and Construction Corps, patients who underwent colonoscopy and colorectal polyps detected were enrolled. The generalized anxiety disorder scale-7 (GAD-7) was used to screen anxiety symptoms, and the patient health questionaire-8 (PHQ-8) was performed to screen depression symptoms, and the general situation questionnaire was used to collect clinical information of patients. The questionnairs were completed via the Questionnaire Star platform or paper questionnaire, and a database was established. The patients were divided into groups according to whether with anxiety and depression symptoms. Multivariable logistic regression models was performed to analyze the factors related to anxiety and depression.Results:A total of 516 questionnaires were distributed and collected, among which 9 questionnaires were incomplete and 507 questionnaires were valid, the effective rate of questionnaires was 98.26%. The detection rates of anxiety and depression symptoms in 507 patients with colorectal polyps were 21.50%(109/507) and 19.33%(98/507), respectively. The results of multivariable logistic analysis revealed that female ( OR=3.87, 95% confidence interval (95% CI) 2.30 to 6.51, P<0.001), maximum diameter of polyp ( OR=1.74, 95% CI 1.14 to 2.67, P=0.011), perception of polyps as cancer ( OR=13.96, 95% CI 1.48 to 132.07, P=0.022), and the occurrence of gastrointestinal symptoms after polyp detection ( OR=5.43, 95% CI 1.74 to 16.92, P=0.004) were independent risk factors of anxiety in patients with colorectal polyps. Female ( OR=2.42, 95% CI 1.47 to 4.00, P=0.001), the number of polyps ( OR=1.07, 95% CI 1.01 to 1.13, P=0.028) and the count of gastrointestinal symptoms ( OR=2.04, 95% CI 1.34 to 3.10, P=0.001) were independent risk factors of depression in patients with colorectal polyps. Conclusion:Gender, polyp size, number of polyps, disease perception, and concomitant gastrointestinal symptoms are associated with anxiety and depression in patients with colorectal polyps.

Effects of radiation therapy on tumor microenvironment: an updated review / 中华医学杂志(英文版)

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.

A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Objectives@#. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. @*Methods@#. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. @*Results@#. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. @*Conclusion@#. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Long-term evaluation and physical and mental effects of residual tinnitus following treatment of sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.

Clinicopathological characteristics and prognosis of non-Hodgkin lymphoma in oral and maxillofacial regions: An analysis of 369 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions.@*METHODS@#Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively.@*RESULTS@#There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients.@*CONCLUSION@#Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.

Application and existing problems of artificial intelligence in oral and maxillofacial surgery / 中华口腔医学杂志

The application of digital technology in the diagnosis and treatment of oral and maxillofacial surgery has promoted the gradual transition from the traditional experience-dependent diagnosis and treatment mode to digital surgery. However, there are some limitations in the application of digital surgical technology. Recently, artificial intelligence has shown tremendous development. The oral and maxillofacial surgery with the goal of digitalization and intelligence has become an important direction of the development of the discipline. Based on the research results domestic and abroad, we discuss the application status and existing problems of artificial intelligence in oral and maxillofacial surgery, in order to promote the further development of artificial intelligence in oral and maxillofacial surgery.

The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

Qianjin Weijingtang in Treatment of Chronic Obstructive Pulmonary Disease： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is a chronic heterogeneous airway disease characterized by persistent and progressive airflow restriction， which can be divided into stable COPD and acute exacerbations of COPD （AECOPD）. Its morbidity and mortality remain high， posing a serious threat to human health. Traditional Chinese Medicine （TCM） believes that COPD belongs to the categories of "cough"， "dyspnea syndrome"， "lung distension"， etc. And its basic pathogenesis is intermingled phlegm and stasis with deficiency in origin and excess in superficiality. Qianjin Weijingtang， derived from the Records of Proved Prescriptions， Ancient and Modern （古今录验方）， consists of Phragmitis Caulis， Persicae Semen， Coicis Semen， and Benincasae Semen， with remarkable functions in clearing the lung， resolving phlegm and eliminating blood stasis， and has definite clinical efficacy in treating COPD and its syndromes. At present， in clinical studies， Qianjin Weijingtang has been used to treat COPD with modifications. It can be used alone or in combination with other prescriptions/western medicines to treat stable COPD， AECOPD， COPD complications， and other TCM syndromes of COPD such as phlegm-heat-stagnation obstructing the lung syndrome. It can significantly improve clinical symptoms， lung function， and blood gas indexes， and inhibit inflammatory response. Animal experiments mainly explored the mechanism of COPD from the level of pathological changes. Specifically， the underlying mechanism may be related to regulating T helper 17 （Th17）/regulatory T cells （Treg） balance， up-regulating single immunoglobulin IL-1-related receptor （SIGIRR） for resisting inflammation， up-regulating hyperplasia suppressor gene （HSG） and inhibiting Wnt signaling pathway activation to inhibit airway remodeling. It was found that there were many problems， such as low quality of clinical research， failure in sharing research standards， and the lack of mechanism research. This article systematically reviewed clinical studies of Qianjin Weijingtang in the treatment of COPD and its mechanism based on animal experiments in recent years， and put forward thoughts and suggestions according to the existing problems to provide references for the clinical application and further research on Qianjin Weijingtang.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis / 中华血液学杂志

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.

Clinical analysis of selective tracheostomy necessary for patients undergoing head and neck surgery with free flap reconstruction / 北京大学学报(医学版)

OBJECTIVE@#To discover the factors that may affect the use of selective tracheostomy among patients who have undergone head and neck surgeries with free flap reconstruction, so that the patients will not need tracheostomy nor receive the unnecessary treatment.@*METHODS@#Five hundred and thirty-three patients who had undergone head and neck surgery with free flap reconstruction operated by the same team of surgery at Department of Oral and Maxillofacial Surgery at Peking University School of Stomatology from 2015 to 2016 were reviewed. Three hundred and twenty-one (60.2%) of these patients underwent selective tracheostomy. All the patients' demographic information, operation-related information, prior treatments, comorbidities and complications were recorded and analyzed.@*RESULTS@#The patients with defects of the tongue, mouth floor, oropharynx and bilateral mandible, who underwent neck dissection and with previous radiotherapy and smoking habit were more likely to get selective tracheostomy. Usage of bulky soft tissue flap might also add to the risk of airway obstruction and the need of selective tracheostomy, while other factors were not significantly related to the risk of postoperative airway obstruction and the patients could be kept safe without selective tracheostomy. Most cases without tracheostomy were kept safe except one case, while 8.39% of the patients with tracheostomy suffered from tracheostomy related complications, mainly pneumonia and hemorrhage of the tracheostomy wound, yet none led to serious consequences or even death.@*CONCLUSION@#Selective tracheostomy is not necessary for patients who have undergone head and neck surgeries with free flap reconstruction except that there are defects at the tongue, oropharynx and mandible. Neck dissection, bulky soft tissue flap reconstruction, previous radiotherapy and smoking habit may also add to the risk of postoperative airway obstruction, while a favorable decision would involve a combination of all the above factors to assure the safety of the postoperative airway for the patients undergone head and neck surgeries with free flap reconstruction.

Clinicopathologic analysis of micro and mini parotid gland tumors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics of micro and mini parotid gland tumors and to provide reference for their clinical diagnosis and treatment.@*METHODS@#Patients with parotid gland tumors treated in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2012 to April 2020 were selected. Relevant clinical data of the patients with tumor diameter ≤20 mm detected by preoperative CT were collected to analyze the clinicopathological characteristics and prognosis of micro and mini parotid gland tumors. And the collected data were divided into two groups with diameter 11-20 mm and diameter ≤10 mm according to tumor diameter measured by preoperative CT. The clinicopathological differences between the two groups were statistically analyzed.@*RESULTS@#A total of 2 067 patients with primary epithelial parotid gland tumors were collected, and 685 patients with tumor diameter ≤20 mm were examined by CT, accounting for 33.1%. The ratio of male to female patients with micro and mini parotid gland tumors was 1 ∶1.93, the average age was (45.3±13.8) years (12-83 years), and the median course of disease was 12 months (1 week to 30 years). Among them, 635 cases (92.7%) were benign tumors, 50 cases (7.3%) were malignant tumors, and the ratio of benign to malignant was 12.7 ∶1. The most common benign tumor was pleomorphic adenoma, and the most common malignant tumor was mucoepidermoid carcinoma. The micro and mini parotid gland tumors were divided into 11-20 mm group (n=611) and ≤10 mm group (n=74), the clinical characteristics comparison of the two groups of gender ratio, average age, course of di-sease had no statistical difference (P>0.05). In the 11-20 mm diameter group, the percentage of benign and malignant tumor was 92.8% (567/611) and 7.2% (44/611) respectively, and the ratio of benign to malignant tumors was 12.9 ∶1. In the ≤10 mm diameter group, the percentage of benign and malignant tumor was 91.9% (68/74) and 8.1% (6/74) respectively, and the ratio of benign to malignant tumors was 11.3 ∶1. There was no significant difference between the two groups (P>0.05). Fifty patients with malignant tumor were followed up for the median follow-up period of 39.5 months (1-91 months). Local recurrence occurred in 2 patients with one death. The overall 2-year survival rate was 93.7% and the 5-year survival rate was 89.3%.@*CONCLUSION@#The majority of micro and mini parotid gland tumors was benign lesion. There was a good prognosis for micro and mini parotid gland carcinoma. Early surgical treatment was recommended for micro and mini parotid gland tumors.

Geospatial analysis of severe road traffic accidents in Singapore in 2013-2014

INTRODUCTION@#Injury is a significant cause of mortality and morbidity. We aimed to investigate which areas in Singapore have a significantly higher incidence of road traffic accidents (RTA) resulting in severe injuries (Tier 1), which is defined as an Injury Severity Score (ISS) greater than 15, and to develop a spatiotemporal model.@*METHODS@#Data was obtained from the National Trauma Registry. The RTA locations were geomapped onto the Singapore map, and spatial statistical techniques were used to identify hotspots with the Getis-Ord Gi* algorithm.@*RESULTS@#From 1 January 2013 to 31 December 2014, there were 35,673 people who were injured as a result of RTAs and 976 Tier 1 RTA victims. A total of 920 people were included in the geospatial analysis. Another 56 were involved in RTAs that did not occur within Singapore or had missing location data and thus were not included. 745 (81.0%) were discharged alive, whereas 175 (19.0%) did not survive to discharge (median ISS 38.00, interquartile range 30.00-48.00). Most of the Tier 1 RTA victims were motorcycle riders (50.1%, n = 461), pedestrians (21.8%, n = 201) and cyclists (9.9%, n = 91). The majority were male and aged 20-40 years, and there was a peak occurrence at 0600-0759 hours. Nine hotspots were identified (p < 0.01).@*CONCLUSION@#Information from studying hotspots of RTAs, especially those resulting in severe injuries, can be used by multiple agencies to direct resources efficiently.

8-Azaguanine-induced autophagy contributes to its chemoresistance in hepatic cancer cells / 药学学报

Autophagy, an evolutionarily conserved process by which components of the cell are degraded in lysosomes, may facilitate survival of cancer cells under stress conditions. 8-Azaguanine (8-AG), an inhibitor of purine nucleotide biosynthesis, shows antineoplastic activity in multiple tumor cells. However, chemoresistance has restricted its development as an anticancer agent, and the mechanism of 8-AG resistance is not fully understood. We report here that 8-AG induces a protective autophagy to eliminate its cytotoxicity, and inhibition of autophagy increases cellular sensitivity of cancer cells to 8-AG treatment. Using HepG2 or SMMC-7721 hepatic cancer cell lines, we found that 8-AG inhibited cell viability and induced intrinsic apoptosis, accompanied by the up-regulation of the pro-apoptotic protein BimS, one of Bim (also known as BCL-2-like protein 11, BCL2L11) isoforms. Furthermore, 8-AG treatment enhanced the autophagy flux by promoting the dephosphorylation and activation of Unc-51-like autophagy activating kinase 1 (ULK1) via Akt/mTORC1 (mammalian target of rapamycin complex 1) signaling inhibition. Depletion of autophagy-related gene 7 (ATG7) markedly enhanced the level of BimS, and promoted cell death in response to 8-AG. 8-AG in combination with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf A1) promoted the 8-AG-induced apoptosis in hepatic cancer cells. Altogether, these findings suggest that autophagy promotes chemoresistance of cancer cells for 8-AG, and blocking autophagy increases cellular sensitivity of cancer cells to 8-AG treatment.

Progress in the correlation between mucin and ocular surface diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Mucin is the key factor to determine the stability of tear film and is crucial to maintain ocular surface homeostasis. Goblet cells can alter the secretion of mucin in corneal and conjunctival epithelial cells, contributing to dry eye disease and ocular surface inflammation. Based on the understanding of mucin biology, this review makes a summary on the potential relationship between mucin dysfunction and ocular surface diseases, and we hope to deepen the understanding of the importance of mucin and select the most appropriate treatment plan on the basis of ocular surface diseases.

Relationship between Changes of Lymphocyte Subsets and Early Hematologic Response in Immunosuppressive Therapy of Severe Aplastic Anemia Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST.@*METHODS@#The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed.@*RESULTS@#There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3@*CONCLUSION@#The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.

Prognostic factors of cyclosporine A combined with androgen in the treatment of transfusion dependent non-severe aplastic anemia / 中华血液学杂志

Objective: To analyze the prognostic factors of transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients treated with cyclosporine A (CsA) and androgen. Methods: Clinical data of 77 consecutive TD-NSAA patients treated with CsA and androgen were retrospectively analyzed between 2010 and 2013. We obtained clinical manifestations and baseline parameters of routine blood test from responders, and compared those with non-responders. All data were analyzed by univariate analysis and multivariate analysis. Results: In 77 patients, there were 43 (55.8%) patients achieved hematological response after 6 months'treatment, and 53 (68.8%) patients got response after 12 months. Univariate analysis showed that platelets baseline was the only factor related to hematological response [19 (6-61) ×10(9)/L vs 13.5 (5-45) ×10(9)/L, P=0.001] after 6 months therapy. After 12 months, the statistical differences were maintained, which were platelets baseline [18 (6-61) ×10(9)/L vs 10.5 (5-45) ×10(9)/L, P<0.001], absolute reticulocytes [0.03 (0.01-0.06) ×10(12)/L vs 0.029 (0.02-0.06) ×10(12)/L, P=0.043], transfusion-dependent of platelet (P=0.007) , transfusion-dependent of platelet and erythrocyte (P=0.012) . Multivariate analysis showed that platelets baseline could be an independent prognostic factor of hematological response (P=0.010 or 0.009) . Cutoff value of platelets by receiver operating characteristic curve was 15.5×10(9)/L. Conclusion: Baseline of higher platelets, higher reticulocyte, and no transfusion dependence of platelet are favorable prognostic factors. When platelets baseline is higher than 15.5×10(9)/L, CsA and androgen regimen is rational.