Adult hemophagocytic syndrome with mutations in UNC13D and MYO5A genes: a case report and literature review / 中国综合临床

Objective:To explore the pathogenesis of primary hemophagocytic syndrome with UNC13D and MYO5A gene mutations.Methods:A case of adult hemophagocytic syndrome with gene mutation of UNC13D and MYO5A admitted to The 940th Hospital of the Joint Logistic Support Force of the PLA on January 28, 2022 was retrospectively analyzed in terms of laboratory examination, gene atlas of its close relatives and prognosis, and related literature was reviewed.Results:The patient was finally diagnosed with primary hemophagocytic syndrome, and chemotherapy was performed twice with hemophagocytic lymphohistiocytosis(HLH)-2004 regimen. The HLA matching of his cytoplasm was semi-compatible. Considering that his cytoplasm carried blood-macrophage related genes, it was not suitable to be selected as a donor, and there were no other suitable relatives. He was transferred to another hospital for allogeneic hematopoietic stem cell transplantation, but failed to receive allogeneic hematopoietic stem cell transplantation during telephone follow-up, and died.Conclusion:The gene mutation of primary hemophagocytic syndrome is the gold standard for the diagnosis of primary HLH. There may be dual gene inheritance pattern in primary HLH, and the combination of immune disorder caused by viral infection and genetic factors may lead to the pathogenesis of primary HLH.

Reflections on the Pain Points of Elderly Care during the Epidemic Prevention and Control Stage from Two Cases of Disease Narration / 中国医学伦理学

The COVID-19 has had a profound impact on human society, the elderly, as a vulnerable group, are the most affected. Based on two cases of disease narrative collected by the department of neurology of a hospital in Guiyang, this paper analyzed the shortcomings of elderly care in the context of epidemic prevention and control. The overall health information literacy of the elderly was low, which made it difficult to obtain correct epidemic related information. The lifestyle of the elderly has changed during the epidemic prevention and control stag. The long time isolation at home has reduced their constitution and made them prone to illness, thus affecting the quality of healthy elderly care. In this stage, the psychological burden of the middle-aged and elderly people has been increasing, which reduced the life satisfaction and subjective well-being of the elderly, and increased the risk of depression. In view of these outstanding problems, this paper proposed corresponding measures, aiming to improve the quality of life and physical and mental health of the elderly during the epidemic prevention and control stage, and provide reference for realizing healthy aging in China.

Application value of nucleic acid testing in syphilis screening reactive blood / 中国输血杂志

【Objective】 To evaluate the application value of nucleic acid testing (NAT) by studying the NAT-yield of syphilis screening reactive blood from five blood centers. 【Methods】 The blood samples and demographic information of syphilis screening positive donors were collected from five domestic blood centers, i. e. Chongqing, Guangxi, Luoyang, Liuzhou, Mianyang and Urumqi. The treponema pallidum particle agglutination (TPPA) and the established SYBR Green qPCR method were used to analyze the difference between the results of NAT and the other two test results. 【Results】 Among 1 679 reactive blood samples for syphilis screening, 819 were confirmed positive by TPPA, accounting for 49%, with the false positive rate exceeded 50%. As to NAT results, the NAT-yield of syphilis screening reactive samples and confirmed positive samples was the same (both 2.20%); the NAT-yield of TPPA-positive and TPPA-negative samples were 2.20% and 2.74%, respectively. 【Conclusion】 Primary syphilis screening by ELISA has high sensitivity, but also presents high false positive rate. Although TPPA confirmatory test has strong specificity, it cannot reflect the existence of T. pallidum. Therefore, NAT may be used as a supplementary test for syphilis screening so as to more effectively ensure the safety of blood transfusion and blood supply.

Different strategies of reducing non-viral nucleic acid of meta-virome in plasma: a comparative study / 中国输血杂志

【Objective】 To explore the influence of common methods of reducing non-viral nucleic acid on the abundance of plasma virus group. 【Methods】 Three kinds of library construction, five kinds of centrifugation conditions, two kinds of filters, four kinds of enzymes and four concentrations of chloroform were used to treat plasma samples added quantitatively 2.16 mL of pseudorabies virus(PRV) and 2.16 mL of porcine parvovirus(PPV). A total of 21.6 mL of plasma samples were processed, including 54 samples. Subsequently, nucleic acid was extracted, mitochondrial DNA(mtDNA) and two viruses were quantitated, the library of the next generation sequencing was constructed, Illumina NovaSeq 6000 was used for the next generation sequencing. The sequencing data were compared with Kraken Py 2.0 software, and the species annotation analysis was conducted. The corresponding species classification information of each segment was obtained to analyze the impact of different reducing non-viral nucleic acid methods on the relative abundance of microorganisms and two indicator viruses. 【Results】 After sequencing by Illumina NovaSeq 6000, 306.27 GB raw data and 193.17 GB clean data were obtained, with Q20>90%, Q30>85%, Error Rate of 0.03%, and average GC Content of 45.02%. The DNA library construction process significantly increased the proportion of microbial sequences and the PRV abundance [(91.8±0.5)%](P<0.05); RNA library construction and combined library construction can increase the abundance of Pestivirus, an RNA virus, and the PRV abundance was(17.7±3.3)% and(8.1±1.5)% respectively. The Ct value of mtDNA was increased and the proportion of human sequence decreased to less than(89.5±1)%, while the proportion of microbial sequence increased to (2.4±0.03)% after treatment of five centrifugation conditions(P<0.05); After centrifugation at 4℃, 100 g, 30 min, the PRV abundance was increased to (40.6±6)%, and centrifugation at 4℃, 4 000 g, 45 min reduced the PRV abundance to (4.1±0.01)%(P<0.05). Both of 0.22-μm filter and 0.45-μm filter increased the Ct value of mtDNA to above 25.56±0.13, decreased the proportion of human sequence to less than (86.1±0.6)%, increased the proportion of microbial sequence to (3.1±0.1)% and (3.4±0.2)%, and decreased the PRV abundance to (1.6±0.3)% and (4.1±0.7)%(P<0.05), while there was no statistical difference in the effect on PPV concentration and abundance. DNase Ⅰ and Benzonase increased the Ct value of PPV to 25.65±0.06 and 25.36±0.45, decreased the proportion of human sequence to (81.7±5.6)% and (72.8±6.7)%, and increased the proportion of microbial sequence and PRV abundance to (11.0±4.1)% and (16.1±4.7)%, (55.8±2.3)% and (39.0±8.9)%, respectively(P<0 05); After treatment with RNase A, the Ct value of PRV increased to 25.20±0.11, and the human sequence proportion decreased to (85.4±5.6)%(P<0 05); Lysozyme had no effect on removing non-viral nucleic acid. The chloroform of 1%, 5%, 10% and 20% increased Ct value of PRV and mtDNA to no less than 27.17±0.21 and 25.68±0.04; Only 10% chloroform increased the proportion of microbial sequences to (3.1±1.2)%(P<0.05); The abundance of PRV with 1% and 5% chloroform treatment was increased to (48.7±13.3)% and (42.1±5.5)%(P<0.05), while 10% and 20% chloroform reduced PRV abundance to (1.0±0.5)% and (3.4±2.8)%(P<0.05). There was no statistical difference in the effect of chloroform with four contents on PPV abundance. 【Conclusion】 Centrifugation at 4℃, 5 000 g, 10 min is suitable for increasing the overall abundance of virus, and centrifugation at 4℃, 100 g, 30 min is suitable for increasing the content of virus similar to PRV. 0.45-μm filter, DNase Ⅰ, Benzonase and low concentration chloroform can effectively reduce the proportion of non-viral nucleic acid sequence in plasma to increase the abundance of the indicated virus group. Thus, the enrichment effect of plasma meta-virome is closely related to the nature of the virus, and the appropriate virus enrichment method should be selected according to the research purpose to establish the corresponding enrichment strategy.

Preparation quality control and clinical application observation of pooled platelets with leukocytes reduced / 中国输血杂志

【Objective】 To investigate the preparation quality and clinical application effect of pooled platelets with leukocytes reduced. 【Methods】 The quality and clinical effect of the buffy-coated method prepared pooled platelets leukocytes reduced (experimental group, n=40) and apheresis platelets leukocytes reduced (control group, n=40) were compared. 【Results】 The platelet volume (mL), platelet count (×1011), red blood cell contamination (×108) and residual white blood cell (×106) of the experimental group and control group were 278.90±7.92 vs 276.52±8.01, 2.66±0.09 vs 2.66±0.83, 0.54±0.42 vs 0.83±0.84, 0.29±0.54 vs 0.27±0.51, respectively, with no significant difference. The results of bacterial culture were negative, all met the requirements of relevant national standards. In addition, the CCI (×103, 24 h) and PPR (%) were 15.11±9.86 vs 14.61±12.55 and 54.23±18.70 vs 61.41±19.09 respectively, with no significant difference, indicating a certain degree of therapeutic effect. 【Conclusion】 The quality and clinical therapeutic effect of pooled platelets leukocytes reduced were consistent with that of apheresis platelets leukocytes reduced.

Detection of platelet bacteria based on cultomics and metagenomics / 中国输血杂志

【Objective】 To explore the composition of culturable bacteria in platelets through bacterial culturomics and verify the results of culturomics and metagenomics to improve the detection rate of bacteria in platelets. 【Methods】 Platelet samples from 6 healthy people were collected. Eight kinds of culture media were placed in aerobic conditions and 12 kinds of culture media were placed in anaerobic conditions for large-scale culture and isolation of bacteria in platelets. The isolated single colony was identified by 16S rRNA gene sequencing. The bacterial abundance of healthy human platelet microbiome was analyzed by metagenomic sequencing, and the cultivable bacterial species in platelets was confirmed based on metagenomic and culturomics results. 【Results】 A total of 90 strains of bacteria belonging to 3 phylums, 5 classes, 5 orders, 7 families, 9 genus and 23 species were isolated from 6 platelet samples by culturomics. Among them, the strains with more monoclonal clones at the species level were Brevundimonas aurantiaca (16.7%), Bacillus sp. Y1 (15.6%), Cutibacterium acnes (14.4%) and Brevibacillus brevis (13.3%). The platelet samples sequenced by mNGS showed that the abundance values of Proteobacteria, Firmicutes and Actinobacteria were high. The bacteria detected by both culturomics and metagenomic sequencing methods were as follows: Firmicutes: Bacillus sp. Y1, B. thuringiensis, B. cereus, B. mobilis, B. velezensis, Staphylococcus epidermidis, and Brevibacillus brevis; Actinobacteria: Cutibacterium acnes; Proteobacteria: Escherichia coli and Delftia tsuruhatensis. 【Conclusion】 The mutual validation of culturomics and metagenomics has identified some bacteria, proving that bacteria exist in platelets.

Progress of diagnosis and treatment for gastrointestinal neuroendocrine neoplasms / 肿瘤研究与临床

Gastrointestinal neuroendocrine neoplasm (GI-NEN) is an important part of digestive system tumor. With the progress of diagnosis and the further understanding of GI-NEN, the diagnostic rate is increasing. However, GI-NEN is a rare tumor, thus clinicians are not familiar with the diagnosis and treatment. Misdiagnosis and missed diagnosis of GI-NEN often occur, and the treatment regimen is not standardized. In recent years, some progresses of the diagnosis and treatment have been made in GI-NEN, especially in the aspects of pathology, imaging diagnosis, radionuclide therapy, targeted therapy and immunotherapy, which have improved the diagnosis rate and efficacy for GI-NEN. This paper reviews recent literatures of GI-NEN, summarizes its epidemiology, pathological diagnosis, image diagnosis, surgery, targeted therapy, radionuclide therapy, chemotherapy, immunotherapy, and separates GI-NEN into metastatic and non-metastatic groups for detailed review to provide a reference for guiding clinical diagnosis and treatment as well as exploring the new treatment regimens of GI-NEN.

Clinical observation of acupuncture with host-guest combination using Yuan-Primordial and Luo-Connecting points plus Tuina for the third lumbar transverse process syndrome / 针灸推拿医学（英文版）

Objective: To observe the effects of acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina (Chinese therapeutic massage) on the third lumbar transverse process syndrome. Methods: A total of 88 patients with the third lumbar transverse process syndrome were selected and divided into an observation group and a control group according to the random number table method, with 44 cases in each group. The control group was treated with Tuina, and the observation group was treated with additional acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination. The clinical efficacy of the two groups was compared after treatment. The changes in the scores of physical signs, Roland-Morris disability questionnaire (RMDQ), Oswestry disability index (ODI), Quebec back pain disability scale (QBPDS), and pain factors [including serum prostaglandin (PG) E2, neuropeptide Y (NPY), and matrix metalloproteinase-3 (MMP-3)] were observed. Results: After treatment, the total effective rate in the observation group was 93.2％, higher than 75.0％ in the control group; the difference between the two groups was statistically significant (P<0.05). Compared with those before treatment, the scores of physical signs and each low back pain scale, and the levels of serum pain factors in the two groups were decreased (P<0.05), and those in the observation group were lower than those in the control group (P<0.05). Conclusion: Acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina is effective in the treatment of the third lumbar transverse process syndrome; it can improve the patient's physical signs, relieve low back pain, and reduce the levels of serum pain factors.

Research Progress on Gene Mutation and CHIP in Pathogenesis of MDS --Review / 中国实验血液学杂志

With the development of molecular biology techniques, the people's understanding of myelodysplastic syndromes (MDS) has greatly improved, a heterogeneous hematopoietic pre-malignant disorder of the stem cells. Gene mutations include RNA splicing, DNA methylation, chromosome modification, transcription factors, signal transduction kinases, RAS pathways, cohesion complexes, DNA repair, etc. Gene mutation is the determinant of diagnostic typing and therapeutic efficacy of MDS. The new concepts of CHIP and ICUS have aroused people's attention to the elderly patients with clonal hematopoiesis and non-clonal cytopenia but without MDS characteristics, who have the possibility of high-risk transformation to MDS and leukemia. In order to better understand the pathogenesis of MDS, the significance of gene mutations, CHIP and ICUS in the diagnosis and prognosis of MDS were reviewed in this paper.

Phenotype and RHD gene polymorphism of 64 Rh negative individuals / 中国输血杂志

【Objective】 To collect blood samples of 64 RhD negative patients in our hospital for RHD genotyping and phenotype analysis (RhC/c/E/e), and analyze the distribution characteristics of different RHD genotypes. 【Methods】 The RHD gene of RhD negative patients was genotyped by fluorescence quantitative polymerase chain reaction (PCR) method. The Rh phenotype was identified by IgM anti-e, anti-c, anti-C and anti-E, respectively. 【Results】 Forty-two cases of RHD deletion were detected, dominated by ccee phenotype (88.1%); 9 of RHD1227A cases, dominated by Ccee phenotype(77.8%); 8 of RHD-CE(3-9)-D2 cases, dominated by Ccee phenotype (75%); 1 of RHD-CE(3-10)-D2 case with Ccee phenotype, 1 of RHD*711delC case; 1 of RHAG site invalid type were detected. The typing results could not be determined in 2 cases by PCR method. 【Conclusion】 RhD negative patients showed diversity in RHD genotype, dominated by RHD deletion, followed by RHD1227A, RHD-CE(2-9)-D2, RHD-CE(3-10)-D2, RHD*711delC and RHAG site deletions.

Establishment and preliminary application of a joint detection method for transplantation-associated infection pathogens / 中国输血杂志

【Objective】 To investigate the effectiveness of multilink real-time fluorescence quantitative PCR (qPCR) in the detection of common pathogens in transplantation. 【Methods】 The primers of the qPCR detection system were designed for 24 common infectious pathogens after clinical transplantation, and the standard plasmids of each pathogen were used to verify the qPCR reaction.After the primer probe effect and concentration of each pathogen reaction system in this experiment was optimized, the sensitivity, correlation coefficient (R2) and amplification efficiency (E) of qPCR method were analyzed and confirmed.Twenty-two samples from patients, who underwent liver and kidney transplantation in transplant ICU of Sichuan Provincial People′s Hospital, were used to verify the application of the detection system.The total nucleic acid of 100 μL was extracted from each individual and divided into two aliquots, which were detected by multi-link qPCR reaction system and analyzed by high-throughput sequencing method (NGS). At the same time, samples (2 mL each) were taken from the transplanted patients for microbial culture.The results of the three detection methods were compared, and the NGS method was taken as the gold standard to analyze the positive detection rate of the multi-link qPCR method and its difference with the culture method and NGS. 【Results】 The lower limit of qPCR detection for 24 pathogens in the established qPCR detection system was 101cp/μL(R2>0.99), with the positive rate of pathogens at 59.1% (13/22), showing significant difference versus microbial culture (18.2%, 4/22)(P<0.05), but not versus NGS (63.6%, 14/22)(P>0.05). Percentage of pathogens detected was as follows: human herpetic virus type 6 (HHV-6) 30.8% (4/13), cytomegalovirus (HCMV) 23.1% (3/13), Epstein-Barr virus (EBV) 23.1% (3/13), human parvovirus B19 15.4% (2/13), Haemophilus influenzae (Hin) 15.4% (2/13), Enterococcus faecium (EFM) 15.4% (2/13), Clostridium difficile 15.4% (2/13), Escherichia coli 7.7% (1/13), Stenotrophomonas maltophilia (Sma) 7.7% (1/13), Klebsiella pneumoniae (Kpn) 7.7% (1/13), Enterococcus faecalis (Efa) 7.7% (1/13) and Streptococcus pneumoniae (Spn) 7.7% (1/13). The consistency rate of pathogens detected by the three methods was 32% (7/22), among which the consistency rate of multi-link qPCR with NGS method was 59% (13/22), and multi-link qPCR with microbial culture was 41% (9/22). 【Conclusion】 Compared with the microbial culture, the multi-link qPCR method demonstrated high sensitivity, accurate quantification, short time and low cost for the detection of common pathogens in clinical transplantation.Multi-link qPCR combined with NGS and microbial culture is helpful to quickly predict the pathogen infection status of patients after transplantation.

HBV genotyping and population genetics analysis of voluntary blood donors in five regions of China / 中国输血杂志

【Objective】 To investigate the distribution of Hepatitis B virus(HBV)genotypes and the genetic characteristics of genotype B HBV populations among voluntary blood donors in five regions of China. 【Methods】 A total number of 630 plasma samples from blood donors with positive HBV HBsAg neutralization test from 2014 to 2016 in Guangxi Blood Center, Chongqing Blood Center, Urumqi Blood Center, Mianyang Central Blood Station and Luoyang Central Blood Station were collected. The S-region sequence of the HBV genome was amplified by semi-nested PCR and followed with Sanger sequencing in order to investigate the HBV genotype distribution and population genetics. 【Results】 Among the voluntary blood donors in five regions, 55 cases of HBV S gene fragments were successfully amplified. Three genotypes were found in HBV typing, including 46 cases of type B(83.64%), 7 cases of type C(12.73%) and 2 cases of type D(3.63%). There were 15 cases of type B and 3 cases of type C in Guangxi; 10 cases of type B and 1 case of type C in Chongqing; 3 cases of type B, 1 case of type C and 1 case of type D in Luoyang; 15 cases of type B in Mianyang; 3 cases of type B, 2 cases of type C and 1 case of type D in Urumqi. The mismatch distribution of the HBVB type population with the largest population number showed a unimodal distribution, and the results of Tajima′s D test and Fu′s Fs test were both negative, indicating that the HBV population in these five regions was expanding. 【Conclusion】 The prevalent genotype of HBV in voluntary blood donors is type B, and the type B HBV population is experiencing a slow expansion, which should attract our attention. In the future, a thorough molecular epidemiological investigation of HBV should be carried out to ensure blood safety.

Recent advances in neonatal Fc receptor targeted drug delivery systems / 药学学报

The neonatal Fc receptor (FcRn) was first found to be a membrane protein that maternal antibodies transmitted to fetuses and newborns, and also expressed in multiple organs and tissues for whole life in adults. It plays a significant role to central regulate the lifespan of immunoglobulin G and serum albumin, as well as its involvement in innate and adaptive immune responses. In modern biopharmaceuticals, FcRn is a great potential drug delivery target and a highlighted subject for current research. This paper briefly describes the basic biological properties and action mechanism of FcRn, as well as the commonly used drug carrier design strategies of FcRn, especially the functional applications of prolonging half-life, targeted drug delivery, transmembrane and antigen presentation and so on. We propose that these distribution in different tissues and the diverse biological activities may have significant implications of targeting FcRn for novel drug delivery systems and immunotherapy.

Effect of psoralen corylifolia on nonalcoholic steatohepatitis in young mice and its possible mechanism / 中国医师杂志

Objective:To study the protective effect and possible mechanism of psoralen corylifolia on non-alcoholic steatohepatitis (NASH) induced by high-fat diet in mice.Methods:The newly weaned female mice in the offspring of C57BL/6J mice fed with normal diet were selected as the control group (gavage of distilled water); the newly weaned female mice in the offspring of C57BL/6J mice fed with high-fat diet were randomly divided into model group (gavage distilled water), low-dose group[psoralen corylifolia 1.125 mg/(g·d)], high-dose group [psoralen corylifolia 2.25 mg/(g·d)] and vitamin E group [vitamin E 0.01 mg/(g·d)]. Six mice in each group were fed continuously for 8 weeks. Automatic biochemical analyzer was used to detect serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), total cholesterol (TC) level in mice; The liver tissue pathological changes were observed by hematoxylin-eosin (HE) and Sirius-red (SR) staining; The level of reactive oxygen species (ROS) in liver tissue was detected by dihydroethidium (DHE) fluorescence probe; the activity of NADPH oxidase was detected by kit; The protein expressions of nuclear factor-κB (NF-κB), phosphatidylinositol 3 kinase (PI3K p85), protein kinase B (Akt), P47 phox and protein kinase C-α (PKC-α) were detected by Western blot.Western blot. Results:The levels of serum ALT, AST, TG, TC and homeostasis model assessment of insulin resistance (HOMA-IR) index in the model group were higher than those in the control group (all P<0.01). After treatment, the levels of serum ALT, AST, TG, TC and HOMA-IR in low-dose group, high- dose group and vitamin E group were lower than those in model group (all P<0.05). HE and SR staining showed that hepatocytes in the model group were swollen, and there were lipid droplets of different sizes, vacuoles and obvious fibrosis. After treatment, hepatocyte steatosis and fibrosis decreased and the contents of ROS and NADPH oxidase in liver decreased(all P<0.05); Western blot showed that the p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox protein expression in the model group were higher than those in the control group (all P<0.01). After treatment, the protein expression levels of p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox decreased (all P<0.01). Among the above indexes, the protective effect of high-dose group on liver NASH was better than those of vitamin E group and low-dose group (all P<0.05). Conclusions:Psoralen corylifolia can improve the liver function of NASH model mice, which may be related to the inhibition of oxidative stress, inflammatory reaction and liver fibrosis, which provides a new idea for the prevention and treatment of children with NASH.

Expert consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine / 中华危重病急救医学

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

Structure‒tissue exposure/selectivity relationship (STR) correlates with clinical efficacy/safety

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

Advances on association between indoor air pollution and 8-hydroxydeoxyguanosine in human urine / 环境与职业医学

8-hydroxydeoxyguanosine (8-OHdG) in human urine is a marker reflecting oxidative stress and DNA oxidative damage. People spend 80%-90% of their life indoors; therefore, indoor air quality is directly related to human health. In this paper, the urinary 8-OHdG levels were presented in populations grouped by different demographic characteristics, lifestyle, occupational exposure, and health status, and elucidated indoor pollutants affecting human urinary 8-OHdG level, such as pollutants from outdoor sources, smoking, indoor combustion and cooking fumes, the chemicals in interior decoration materials, and building foundation soils. The article aims to provide a theoretical basis for predicting the impact of indoor air pollution on human health (DNA oxidative damage and related diseases) by measuring the concentration of 8-OHdG in human urine.

Cortical 5-hydroxytryptamine receptor 3A (Htr3a) positive inhibitory neurons: diversity in type and function / 生理学报

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a

Absence of BAX differentially affects astrocyte density in the mouse cortex and hippocampus / 生理学报

Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.

Emerging infectious diseases in voluntary blood donors in parts of China: Based on metagenomics analysis / 中国输血杂志

【Objective】 To analyze the metagenomics and microbiology of voluntary blood donors in China, so as to assess the potential threats of emerging infectious diseases to the safety of blood transfusion. 【Methods】 12 300 plasma samples (10 mL each) collected by central blood stations in Chongqing, Liuzhou, Urumqi, Mianyang, Wuhan, Nanjing, Mudanjiang, and Dehong Prefecture area from 2012 to 2018 were subjected to total DNA extraction after ultracentrifugation (32 000 rpm/min, centrifugal radius 91.9 mm) in minipools of 160 donations. The metagenomic library was constructed, and deep sequencing was conducted by Illumina Hiseq 4 500. By comparing with reference sequences of bacteria, fungi, parasites and viruses, metagenomic data were analyzed, classification of microbes were identified, and potentially harmful pathogens were evaluated. 【Results】 A total of 632 GB clean data were obtained by deep sequencing, and the top three pathogens were Pseudomonas(0.561 1%), Burkholderia(0.468 7%) and Serratia(4.242 0%). Pathogens with potential threat which could be transmitted by blood transfusion or blood products were found, such as human parvovirus B19(0.126 6%), Leishmania spp(1.348 5%) and Toxoplasma gondii(0.615 8%). 【Conclusion】 Our study analyzed metagenomics of voluntary blood donors in parts of China and revealed pathogens that may cause potential harm to blood safety, which were helpful for targeted prevention and control of emerging infectious diseases.