Benzodiazepines in complex biological matrices:Recent updates on pretreatment and detection methods / 药物分析学报

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS / 药物分析学报

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

The efficacy of neuroendoscope-assisted drainage with lumbar cistern and large bone flap decompression in the treatment of craniocerebral trauma complicated with temporal uncinate herniation / 中国医师进修杂志

Objective:To observe the effect of neuroendoscope-assisted drainage with lumbar cistern and large bone flap decompression in the treatment of craniocerebral injury complicated with temporal uncinate herniation.Methods:A total of 80 patients with craniocerebral trauma and temporal uncinate herniation hospitalized in Lanling County People′s Hospital from January 2017 to October 2020 were retrospectively included and divided into the observation group and the control group according to the surgical methods, with 40 patients in each group. Surgical procedures were performed by the same group of experienced neurosurgeons. The observation group was treated with neuroendoscope-assisted drainage with lumbar cistern and large bone flap decompression, while the control group was treated with large bone flap decompression only. Cephalic CT was reexamined before and 48 h after the surgery to compare the appearance rates of cisterna ambiens and suprasellar cistern. Intracranial pressure (ICP) was monitored at 3, 5 and 7 d after the surgery, and the scores of Glasgow coma scale(GCS) was recorded. Drainage time, postoperative cerebral edema and cerebral infarction complications were recorded and compared between the two groups. Six months after the surgery, the prognosis was assessed by the Glasgow prognostic scale (GPS).Results:The occurrence rates of cisterna ambiens and suprasellarcistern in the observation group were higher than those in the control group: 67.50%(27/40) vs. 45.00%(18/40), 65.00%(26/40) vs. 42.50%(17/40), χ2 = 4.11, 4.07, P<0.05. The ICP value in the observation group at 3, 5 and 7 d after the surgery were significantly lower than those in the control group, and the scores of GCS in the observation group were significantly higher than those in the control group, there were statistical differences( P<0.05). There was no statistically significant difference in drainage time between the two groups ( P>0.05). The incidence of postoperative cerebral edema in the observation group was lower than that in the control group:7.50%(3/40) vs. 25.00%(10/40), χ2 = 4.50, P<0.05. The incidence of postoperative cerebral infarction in the observation group was lower than that in the control group, and the volume of cerebral infarction was smaller than that in the control group: 5.00%(2/40) vs. 22.50%(9/40), (6.68 ± 1.75) cm 3 vs. (8.20 ± 2.15) cm 3, there were statistical differences ( P<0.05). The incidence of postoperative complications in the observation group was lower than that in the control group: 7.50%(7/40) vs. 40.00%(16/40), χ2 = 4.94, P<0.05. Six months after the surgery, the rate of good prognosis in the observation group was higher than that in the control group: 62.50%(25/40) vs. 35.00%(14/40), χ2 = 6.05, P<0.05. Conclusions:Neuroendoscope-assisted drainage with lumbar cistern and large bone flap decompression in the treatment of craniocerebral trauma and temporal uncinate herniation has good efficacy and safety.

Diurnal variation of serum hypoxia inducible factor-1 α in obese patients with obstructive sleep apnea / 国际外科学杂志

Objective:To observe the diurnal changes of serum hypoxia inducible factor-1α (HIF-1α) and its relationship with polysomnography (PSG) parameters in obese patients with obstructive sleep apnea (OSA).Methods:In this study, 64 obese subjects with OSA (experimental group) and 24 normal subjects (control group) were included. PSG monitoring was performed in all subjects, and peripheral blood samples were collected at night and next early morning to detect the expression level of HIF-1 α mRNA and protein concentration in serum. The data were analyzed by SPSS25.0 software. The counting data was represented by n(%), and t-tests were used for inter group comparisons. The measurement data of normal distribution adopted mean ± standard deviation ( ± s), and the inter group comparison adopted Chi-square. Serum HIF-1α mRNA levels and protein concentrations in the two groups were compared and analyzed by Two-way ANOVA, and Spearman rank correlation was used to analyze the correlation. Results:The ratio of male to female in the control group was 15: 9 and the average age was (39.25 ±10.58) years old, while that in the experimental group was 41∶24 with an average age of (41.31 ±15.20) years. The body mass index (BMI) of experimental group was higher, while all the relevant parameters recorded by PSG were significantly different between two groups ( P<0.001). The results showed that there was no significant difference in the expression of HIF-1α mRNA between the control group and the experimental group ( P=0.914), or between night and morning ( P=0.167). The concentration of HIF-1α protein in the control group was significantly lower than that in the experimental group ( P<0.001), but there was no significant difference in the concentration of HIF-1α protein in the same group at night and in the morning ( P=0.798). The results of correlation analysis showed that there was a significant correlation between PSG related indexes(AHI, minimum blood oxygen, mean blood oxygen and SIT90), night and morning mRNA expression and protein concentration ( P<0.05). Conclusions:Compared with normal people, the concentration of serum HIF-1 α protein in obese patients with OSA is higher, but there is no difference between night and morning. The process of HIF-1 α induced by CIH may be involved in post-translational regulation rather than transcription, and other compensatory mechanisms may also be involved.

A retrospective analysis of occupational pneumoconiosis in Zibo City from 1949 to 2021 / 中国职业医学

Objective: To analyze the base incidence, distribution characteristics, survival status and social security of occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Zibo City. Methods: The new pneumoconiosis patients in Zibo City from 1949 to 2021 were selected as the research subjects using a cross-sectional survey. Household survey or telephone follow-up were carried out, and the distribution characteristics, living conditions and social security situation were retrospectively analyzed. Results: A total of 8 910 patients with pneumoconiosis were investigated, and 96.0% of them were male. The stage Ⅰ pneumoconiosis patients accounted for 91.3%. From 1949 to 2021, the number of pneumoconiosis patients showed a stepwise upward trend with time. Most of the patients suffered from coal worker pneumoconiosis and silicosis, which accounted for 48.7% and 38.9%, respectively. The average age of onset was (52.7±11.4) years, and the average length of service exposed to dust was (21.1±9.4) years. The patients were concentrated in Zichuan District, Boshan District and Zhangdian District, that accounted for 87.8%. The industry distribution was mostly mining industry and manufacturing industry, accounting for 61.1% and 31.6% respectively. Among the 8 910 cases of pneumoconiosis, 543 cases were lost in follow-up. A total of 8 367 patients were followed-up, with a follow-up rate of 93.9%. The mortality rate of patients who completed follow-up was 50.5%, and the mortality rate decreased with the increase of the stage of pneumoconiosis (P<0.01). The rate of adoring social security in the 4 138 surviving patients was 98.4%. Conclusion: The situation of prevention and treatment of pneumoconiosis in Zibo City is challenging. It is necessary to strengthen the special control of dust hazards in mining and manufacturing industries in key areas such as Zichuan District, Boshan District and Zhangdian District.

Management of anticoagulant therapy in a patient with complex venous thromboembolism complicated with acute renal insufficiency / 中国药房

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.

A survey of interventional radiology resources and radiation protection equipment and personal dosimeter wearing rate in Qingdao, China / 中国辐射卫生

Objective To investigate the current status of interventional radiology resources, radiation protection equipment, and the rate of wearing of personal dosimeters in Qingdao, China, and to provide a data basis for strengthening radiation protection and health management for interventional radiation workers. Methods A questionnaire survey was performed on all medical institutions with interventional radiation services in Qingdao. The data from April 1, 2020 to March 31, 2021 were pooled and analyzed. Results A total of 31 medical institutions in Qingdao were investigated, including 23 (74.20%) tertiary hospitals and 8 (25.80%) secondary hospitals. There were 88 pieces of interventional radiation equipment in total in Qingdao, 89.77% of which were in tertiary hospitals. A total of 921 interventional professionals participated, with 865 (93.92%) from tertiary hospitals and 56 (6.08%) from secondary hospitals. The mean annual number of visits to interventional services was 5.72 per 1000 people. Among personal protective equipment, the equipment rates of lead-rubber aprons, lead-rubber caps, and lead-rubber collars were highest, all being 100%. The rate of equipment of interventional protective gloves was lowest, which was only 51.61%. The mean number of each accessory protective equipment for each interventional machine was less than 1. The rate of wearing of dual-dosimeters was 84.36%. Conclusion Tertiary hospitals were dominant among the medical institutions in this survey of interventional radiology services in Qingdao. The most frequently equipped personal protective goods were lead-rubber aprons, caps, and collars. The equipment rates of interventional protective gloves and protective accessories and the rate of wearing of dual-dosimeters were relatively low.

A survey on the current status of cognition of birth safety among married HIV-infected people aged 18-45 years / 中华流行病学杂志

Objective: To understand the current status of fertility safety cognition among married HIV-infected people aged 18-45 years and to provide evidence for fertility safety intervention in HIV-infected families. Methods: Six districts in Chongqing and Zigong City in Sichuan Province were selected. A questionnaire survey was conducted among married HIV-infected people aged 18-45 years who were followed up from November 2021 to April 2022 to collect their general demographic characteristics, histories of sex experience, fertility intention, and knowledge of birth safety. Unconditional logistic regression and Poisson regression were used to analyze the factors affecting the cognition of birth safety. Results: A total of 266 HIV-infected people were included in the study; 58.3% (155/266) were women, and 48.9% (130/266) had fertility desire. The cognition rate of knowledge of birth safety was 59.4% (158/266). The cognition rate of women's knowledge of birth safety was 2.14 (95%CI: 1.25-3.66) times that of men's. The cognition rate of knowledge of birth safety among HIV-infected persons with a high school education level or above was 1.88 (95%CI: 1.08-3.27) times that of those with a low education level. The cognition rate of knowledge of reproductive safety among HIV-infected people with fertility intention was 1.88 (95%CI: 1.10-3.22) times that of those without fertility intention. The cognition rate of knowledge of birth safety among HIV-infected persons who received AIDS knowledge promotion and education was 9.06 (95%CI: 2.46-33.32) times that of those who did not. The cognition rate of measures of birth safety was 5.3% (14/266). The Poisson regression analysis showed no significant difference in the cognition rate of specific measures among gender, age, education and other factors. Conclusions: HIV-infected people aged 18-45 years and married with a spouse have a low awareness of birth safety, and there are risks of HIV transmission between couples and mother-to-child in the family. Targeted birth safety education and intervention should be strengthened to reduce HIV transmission.

Research status of traditional Chinese medicine regulating Th17/Treg balance in the treatment of rheumatoid arthritis / 中国药房

Rheumatoid arthritis （RA） is a refractory autoimmune disease that can cause symmetrical polyarticular disease. The key mechanism of its occurrence and development is the dysequilibrium of helper T cell 17 （Th17）/regulatory T cell （Treg） balance. Therefore， reconstructing Th17/Treg balance may be a new strategy for the treatment of RA. Traditional Chinese medicine has significant advantages in the treatment of RA such as integrity， multi-target， multi-link and multi-path. This paper summarizes the basic and clinical studies on the regulation of Th17/Treg balance in the treatment of RA by traditional Chinese medicine in the past five years， and finds that the active components/sites of traditional Chinese medicine such as flavonoids， alkaloids and terpenes have unique advantages in the regulation of Th17/Treg balance. The traditional Chinese medicine compound formula interferes with Th17/Treg balance by exerting the effects of dispelling wind， dehumidifying， removing blood stasis， unblocking collaterals， relieving pain， dispersing cold and strengthening health. The effect of external treatment of traditional Chinese medicine is obvious and can be used as a clinical adjuvant therapy for RA； related mechanisms of action include regulating the production of inflammatory factors， regulating the expression of transcription factors and interfering with the activation of signaling pathways. However， the existing research has the shortcomings of insufficient mechanism research， few clinical research， limited external treatment research of traditional Chinese medicine， and lack of combination therapy research， which need to be improved by follow- up research.

Fipronil and its metabolites in indoor dust in Shenzhen in 2020 -2021: analysis of residual levels and temporal variations / 公共卫生与预防医学

Objective To explore the residual level of FPMs in indoor dust samples in Shenzhen from 2020 and 2021, and to analyze its temporal distribution characteristics. Methods In the present study, indoor dust samples (n=193) from residential buildings in Shenzhen. were collected to analyze the temporal variation characteristics of FPMs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to determine the concentrations of FP and its four major metabolites (fipronil-sulfone, fipronil-sulfide, fipronil-desulfinyl, and fipronil-amide; abbreviated as FP-SFO, FP-SFI, FP-DES, and FP-AM) in the samples. The sum of the concentrations of FP and its four metabolites was represented as additive mass concentration (ΣFPMs). Additionaly, Wilcoxon test was performed to determine the temporal distribution differences of FPMs’ concentrations. Results From 2020 to 2021, the concentration of ΣFPMs for the in door dust samples in Shenzhen ranged from 0.51 to 4 415 ng/g (median: 18.8ng/g). FP, FP-SFO AND FP-SFI were the major target analytes in the sample with detection rates of 90.60%，86.20% and 75.40%, respectively. The detection rates of other metabolites were low (≤ 44.3%). Analysis of the temporal variation trend of FPMs’ concentrations showed that there was no significant difference in the levels of ΣFPMs between warm season（spring and summer）and cold season（autumn and winter）in the indoor dust samples from 2020 to 2021(2.38 vs 2.84ng/g , P > 0.05). However , the concentrations of FP-SFI and ΣFPMs in the indoor dust samples collected from 2021 showed an significantly increasing trend compared with 2020（1.02 vs 1.89 , 17.80vs. 20.10 ng/g , P < 0.05). Conclusion From 2020 to 2021 , the detection level of FPMs in indoor dust in Shenzhen is relatively high and shows an upward trend , with no obvious seasonal difference. However, whether the residual level of FPMs in indoor dust poses a risk to human health needs further study.

Antitumor of Main Active Components of Poria： A Review / 中国实验方剂学杂志

ObjectiveMalignant tumor has become a serious public health problem， threatening human health. Chinese herbal medicine has become a research focus as it is "simple， convenient， inexpensive， and effective" and exerts anti-tumor effect through "multiple components， multiple targets， and multiple pathways". This paper reviews the anti-tumor effect of triterpenes， polysaccharides and other compounds in Poria， which is expected to serve as a reference for research on the anti-tumor effect of Poria. MethodBasic research， clinical observation， and reviews were retrieved from PubMed， Google Scholar， and China National Knowledge Infrastructure （CNKI） （1995—2022） with the keywords of Poria and malignant tumor. ResultThe main active components of Poria such as triterpenes represented by pachymic acid and polysaccharides represented by pachyman had extensive pharmacological effects in inhibiting the proliferation of malignant tumors， inducing apoptosis， suppressing invasion and metastasis， regulating the immune function， and improving the quality of life. In addition， the cultivation method， medicinal part， growth environment， and harvest cycle of the medicinal plant， and dosage form and processing method of Poria affected the content of different active components. ConclusionThe active components of pachymic acid and triterpenoids have great potential in antitumor， which， however， face the challenges in innovation and quality clinical trials. The lack of quality control standard of Poria may affect the anti-tumor effect， and efforts should be made to formulate specific standard for quality control. The antitumor of Poria is science-based and thus it has broad application prospect. Nevertheless， more efforts should be made before the practical application.

Management strategy of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis and a literature review / 中国药房

OBJECTIVE To provide reference for the management of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis. METHODS The clinical pharmacist participated in the treatment of a thrombocytopenia patient with atrial fibrillation and atherosclerosis， and analyzed the causes of thrombocytopenia according to the patient’s medical history and laboratory examination results. At the same time， the risk of thrombosis-bleeding was evaluated according to the relevant guidelines， and the clinicians were assisted in formulating individual antithrombotic therapy plan and pharmaceutical care plan for the patient. The literature on antithrombotic therapy related to thrombocytopenia was collected and analyzed by retrieving CNKI. RESULTS Thrombocytopenia was considered as primary thrombocytopenia in this patient， and the main risk of bleeding was age ≥65 years old， bleeding tendency， and combined use of antithrombotic drugs. After the clinical pharmacist assessed the risk of thrombosis and bleeding， the clinician was recommended to give full dose of Bemiheparin sodium injection + Dronedarone hydrochloride tablets + Metoprolol succinate sustained-release tablets. In view of thrombocytopenia， the clinician gave Compound zaofan pill， Caffeic acid tablet and Sheng xuexiaoban capsule， but the patient developed diarrhea after the medication. The clinical pharmacist suggested stopping Sheng xuexiaoban capsule， and the clinician adopted the clinical pharmacist’s suggestion. When the patient was discharged from hospital， the clinical pharmacist suggested that the antithrombotic therapy plan for discharge was anticoagulation alone or selective anticoagulation. The clinician chose selective anticoagulation treatment considering that the patient’s current thrombocytopenia， urinary occult blood （+） and fecal occult blood were weakly positive， and ordered the patient to take Metoprolol succinate sustained-release tablets + Atorvastatin calcium tablets at discharge. Literature analysis showed that the causes of thrombocytopenia of patients with thromboembolism mainly included heparin induced-thrombocytopenia， immune thrombocytopenia， etc. All patients were improved after symptomatic treatment. CONCLUSIONS By participating in the management of antithrombotic therapy for the thrombocytopenia patient with atrial fibrillation and atherosclerosis， clinical pharmacists can help effectively control the patient’s condition and ensure the safety and effectiveness of drug use.

Development of a tau-V337M mouse model using CRISPR/Cas9 system and enhanced ssODN-mediated recombination / 生物工程学报

The generation of a tau-V337M point mutation mouse model using gene editing technology can provide an animal model with fast disease progression and more severe symptoms, which facilitate the study of pathogenesis and treatment of Alzheimer's disease (AD). In this study, single guide RNAs (sgRNA) and single-stranded oligonucleotides (ssODN) were designed and synthesized in vitro. The mixture of sgRNA, Cas9 protein and ssODN was microinjected into the zygotes of C57BL/6J mice. After DNA cutting and recombination, the site homologous to human 337 valine (GTG) in exon 11 was mutated into methionine (ATG). In order to improve the efficiency of recombination, a Rad51 protein was added. The female mice mated with the nonvasectomy male mice were used as the surrogates. Subsequently, the 2-cell stage gene edited embryos were transferred into the unilateral oviduct, and the F0 tau-V337M mutation mice were obtained. Higher mutation efficiency could be obtained by adding Rad51 protein. The F0 tau-V337M point mutation mice can pass the mutation on to the F1 generation mice. In conclusion, this study successfully established the first tau-V337M mutation mouse by using Cas9, ssODN and Rad51. These results provide a new method for developing AD mice model which can be used in further research on the pathogenesis and treatment of AD.

Metabolic engineering of Escherichia coli for adipic acid production / 生物工程学报

Adipic acid is a high-value-added dicarboxylic acid which is primarily used in the production of nylon-66 for manufacturing polyurethane foam and polyester resins. At present, the biosynthesis of adipic acid is hampered by its low production efficiency. By introducing the key enzymes of adipic acid reverse degradation pathway into a succinic acid overproducing strain Escherichia coli FMME N-2, an engineered E. coli JL00 capable of producing 0.34 g/L adipic acid was constructed. Subsequently, the expression level of the rate-limiting enzyme was optimized and the adipic acid titer in shake-flask fermentation increased to 0.87 g/L. Moreover, the supply of precursors was balanced by a combinatorial strategy consisting of deletion of sucD, over-expression of acs, and mutation of lpd, and the adipic acid titer of the resulting E. coli JL12 increased to 1.51 g/L. Finally, the fermentation process was optimized in a 5 L fermenter. After 72 h fed-batch fermentation, adipic acid titer reached 22.3 g/L with a yield of 0.25 g/g and a productivity of 0.31 g/(L·h). This work may serve as a technical reference for the biosynthesis of various dicarboxylic acids.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

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.

COL4A5 genotypes and clinical characteristics of children with Alport syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS).@*METHODS@#A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations.@*RESULTS@#Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset.@*CONCLUSIONS@#This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

Primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement: A case report and surgical techniques / 中华创伤杂志(英文版)

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.

Meta-analysis of the effect of hollow nail and bone plate on Lisfranc injury / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of screw and bone plate internal fixation in the treatment of Lisfranc injury.@*METHODS@#The databases of Wanfang, CNKI, Pubmed, EMBASE, VIP, BIOSIS and other databases were retrieved by computer, and the clinical trial literature from January 1, 2000 to August 1, 2021 was retrieved, the methodological quality of the included studies was strictly evaluated and the data were extracted, and the obtained data were meta-analyzed by Revman 5.4 software.@*RESULTS@#Nine randomized controlled trial literature and 10 retrospective cohort studies were included, of which 416 patients in the experimental group were treated with screw internal fixation, and 435 patients in the control group were treated with bone plate internal fixation. Meta-analysis showed that the surgical time of the bone plate internal fixation group was longer than that of the screw internal fixation group [MD=-14.40, 95%CI(-17.21, -11.60), P<0.000 01], the postoperative X-ray anatomical reduction of the bone plate internal fixation group [MD=0.47, 95%CI(0.25, 0.86), P=0.01], the excellent and good rate of postoperative American orthopedic foot and ankle society(AOFAS) foot function score[MD=0.25, 95%CI(0.15, 0.42), P<0.000 01], postoperative AOFAS foot function score [MD=-5.51, 95%CI(-10.10, -0.92), P=0.02] of the bone plate fixation group was better than those of the screw internal fixation group. Two kinds of operation method had no statistical different for postoperative fracture healing time[MD=1.91, 95%CI(-1.36, 5.18), P=0.25], postoperative visual analgue scale(VAS)[MD=0.38, 95%CI(0.09, 0.86), P=0.11], postoperative complications [MD=1.32, 95%CI(0.73, 2.40), P=0.36], the postoperative infection [MD=0.84, 95%CI(0.48, 1.46), P=0.53], the postoperative fracture internal fixation loosening [MD=1.25, 95% CI(0.61, 2.53), P=0.54], the postoperative incidence of traumatic arthritis [MD=1.80, 95%CI(0.83, 3.91), P=0.14].@*CONCLUSION@#Bone plate fixation has better short-term and medium-term results and lower reoperation rate in the treatment of Lisfranc injury, so it is recommended to use bone plate fixation in the treatment of Lisfranc injury.

Efficacy of micro steel plate and Kirschner needle oblique and transverse internal fixation of adjacent metacarpal bone in the treatment of metacarpal diaphyseal oblique fracture / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of micro steel plate and Kirschner needle oblique and transverse internal fixation of adjacent metacarpal bone in the treatment of metacarpal diaphyseal oblique fracture.@*METHODS@#Fifty-nine patients with metacarpal diaphyseal oblique fractures admitted between January 2018 and September 2021 were selected as the study subjects and divided into the observation group (29 cases) and the control group (30 cases) based on different internal fixation methods. The observation group was treated with Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones, while the control group was treated with micro steel plate internal fixation. Postoperative complications, operation time, incision length, fracture healing time, treatment cost, and metacarpophalangeal function were compared between the two groups.@*RESULTS@#No incision or Kirschner wire infections occurred in the 59 patients, except for one in the observation group. No fixation loosening, rupture, or loss of fracture reduction occurred in any of the patients. The operation time and incision length in the observation group were (20.5±4.2) min and (1.6±0.2) cm, respectively, which were significantly shorter than those in the control group (30.8±5.6) min and (4.3±0.8) cm (P<0.05). The treatment cost and fracture healing time in the observation group were (3 804.5±300.8) yuan and (7.2±1.1) weeks, respectively, which were significantly lower than those in the control group (9 906.9±860.6) yuan and (9.3±1.7) weeks (P<0.05). The excellent and good rate of metacarpophalangeal joint function in the observation group was significantly higher than that in the control group at 1, 2, and 3 months after operation (P<0.05), but there was no significant difference between the two groups at 6 months after operation (P>0.05).@*CONCLUSION@#Micro steel plate internal fixation and Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones are both viable surgical methods for treating metacarpal diaphyseal oblique fractures. However, the latter has the advantages of causing less surgical trauma, shorter operation time, better fracture healing, lower cost of fixation materials, and no need for secondary incision and removal of internal fixation.