Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the ≤ 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Objective:To summarize the clinical characteristics and first aid measures of children with drowning，and to provide scientific basis for the treatment and prevention of drowning in children.Methods:The clinical data of drowning children admitted to the Children's Medical Center of the First Affiliated Hospital of Hunan Normal University（Hunan Provincial People's Hospital）from January 2011 to December 2021 were retrospectively summarized. Baseline characteristics，prehospital emergency care and prognosis of the included children were analyzed.According to the time span, drowning children were divided into two stages, the first stage (2011-2016) and the second stage (2017-2021). According to cerebral performance category assessment scale,drowning children with cardiac arrest were divided into two groups: a group with good neurological prognosis and a group with poor neurological prognosis. The baseline characteristics,pre-hospital emergency care, and prognosis of drowning children during different periods and with different prognosis were analyzed.Results:A total of 53 children were enrolled during the study period，with 24 cases in the first phase（2011-2016）and 29 cases in the second phase（2017-2021）.Boys accounted for 73.6%（39/53）of the cases, the age ranged from 1 month and 24 days to 14 years old，with 1-4 years old being the most common，accounting for 58.5%（31/53）, and the season in which drowning occurred was more common in the summer（39.6%, 21/53）.Six cases (11.3%) had significant neurological sequelae, and the mortality rate was 3.8%（2/53）.There was a decrease in the proportion of drowning with water control in the second stage compared to the first stage（37.5% vs. 13.79%, P=0.046）.Thirty-two（60.4%）children experienced on-site cardiopulmonary resuscitation(CPR) after drowning，with 24 cases in the group with good neurological prognosis and 8 cases in the group with poor neurological prognosis.Children in the poor neurological prognosis group required CPR for a long duration [10.00（1.50, 25.00）min]，had lower body temperature，Glasgow Coma Score，pH and higher blood glucose levels on admission（all P < 0.05）. Conclusion:Drowning is most common in preschool children，common in boys，and drowning prevention measures for young children deserve focused attention. Children found to be in cardiac arrest at the time of drowning have a long duration of drowning and CPR，which predicts a poor neurological prognosis，and timely and effective on-site CPR is the key to reducing the drowning rate.

Objective To investigate the effect of the HtrA serine peptidase 3(HTRA3)gene on choroidal neovascu-larization(CNV)and M2 macrophage polarization.Methods Fasting venous blood was collected from 30 patients with wet age-related macular degeneration(wAMD group)and 30 healthy subjects(normal group).The serum HTRA3 messen-ger ribonucleic acid(mRNA)level was detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RF/6A cells were randomly divided into the control group,NC-sh group and HTRA3-sh group.Lentiviral vectors of NC-shRNA and HTRA3-shRNA were transfected into RF/6A cells in the NC-sh group and HTRA3-sh group by Lipo-fectamine2000.HTRA3 transfection was detected by qRT-PCR and Western blot.Then,the RF/6A cells were randomly di-vided into the N group,H group,H+NC-sh group and H+HTRA3-sh group.After cell transfection,RF/6A cells in the N group were cultured in a RPMI 1640 complete medium at a normoxia state,and cells in other groups were cultured in a RP-MI 1640 medium with 200 mmol·L-1 CoCl2 at a hypoxia state.Tubule formation was measured by Matrigel.The C57BL/6J mice were divided into the control group,CNV group,CNV+NC-sh group and CNV+HTRA3-sh group,with 12 mice in each group.Mice in the control group were unmodeled mice,and mice in the other groups were laser-induced CNV model mice.NC-shRNA and HTRA3-shRNA lentiviral vectors with a titer of 1 × 1011 TU·mL-1 were administered to mice in the CNV+NC-sh group and CNV+HTRA3-sh group via intravitreal injection.Mice in the control group and CNV group were in-jected with phosphate buffered saline.After 7 days of treatment,the mice were examined by fundus fluorescein angiogra-phy,and the eyeballs received hematoxylin & eosin staining.The mRNA levels of HTRA3,chitinase-like protein 3(Ym-1),arginase 1(Arg-1),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and vascular endothelial growth factor(VEGF)in RF/6A cells or choroidal tissues were detected by qRT-PCR.The protein expression levels of HTRA3,VEGF and nuclear factor kappa B(NF-κB)p65 in RF/6A cells or choroidal tissues were detected by Western blot.Re-sults Compared with the normal group,serum HTRA3 mRNA level of patients in the wAMD group increased(t=11.804,P＜0.001).Compared with the control group and NC-sh group,the expressions of HTRA3 mRNA and protein in RF/6A cells in the HTRA3-sh group decreased(all P＜0.05).Compared with the N group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF in RF/6A cells in the H group increased(all P＜0.05).Compared with the H+NC-sh group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF decreased in RF/6A cells in the H+HTRA3-sh group(all P＜0.05).Compared with the control group,the mRNA and protein expression levels of HTRA3 increased,the relative fluorescence intensity of CNV increased,the mRNA levels of Ym-1 and Arg-1 in-creased,the iNOS and COX-2 mRNA levels decreased,and the NF-κB p65 protein expression level increased in mice of the CNV group(all P＜0.05).Compared with the CNV+NC-sh group,the mRNA and protein expression levels of HTRA3 de-creased,the relative fluorescence intensity of CNV decreased,the mRNA levels of Ym-1 and Arg-1 decreased,the mRNA levels of iNOS and COX-2 increased,and the NF-κB p65 protein expression level decreased in mice of the CNV+HTRA3-sh group(all P＜0.05).Conclusion Down-regulation of HTRA3 can inhibit the formation of CNV and the polarization of M2 macrophages.HTRA3 may be an important potential target for the prevention and treatment of wAMD.

Metal-organic frameworks (MOFs) are crystalline materials with a multidimensional porous network structure, formed through coordination bonds with metal ions as nodes and organic ligands as connecting bridges. Due to their excellent physicochemical properties, MOFs have extensive applications in the field of biomedicine, ranging from antibacterials, drug carriers, imaging to sensors. Nanoscale metal-organic frameworks (nMOFs), commonly utilized drug carriers, can gain enhanced safety, targeted delivery, and superior therapeutic effect through endocytosis. In this review, we comprehensively summarize the factors influencing the endocytosis of nMOFs, focusing on three key physicochemical properties, particle size, morphology and surface modification. Based on different illness models, the review succinctly summarizes the latest advancements in understanding the endocytosis pathways of nMOFs while critically reflecting on the inherent limitations of current research methods. Lastly, the review offers valuable insights into future research methodologies and objectives, aiming to lay the groundwork and provide meaningful guidance for the synthesis and development of nMOFs as promising versatile drug carriers.

  Objective  To investigate the occurrence of chronic postsurgical pain (CPSP) among patients with preoperative COVID-19, and further analyze the risk factors for CPSP.  Methods  This study was a ambispective cohort study, with subjects from a completed cohort study with follow-up. We included the clinical data of the patients with preoperative COVID-19 who underwent surgery at Peking Union Medical College Hospital from December 1, 2022 to February 28, 2023. Follow-up was conducted up to 6 months postoperatively, with the primary outcome being CPSP. Multivariate Logistic regression analysis was used to analyze the correlation between COVID-19-related exposure indicators and CPSP.  Results  A total of 4117 surgical patients were included, all of whom had preoperative COVID-19. Among them, 4002 cases had mild symptoms during the acute phase, 62 cases had severe symptoms, and 53 cases were critically ill. At 6th month postoperatively, 1298 cases (31.53%) had long COVID-19 syndrome, and the incidence of CPSP was 5.59% (95% CI: 4.88%-6.28%). After adjusting for confounding factors including age, gender, comorbidities, anesthesia method, and type of surgery, multivariate Logistic regression analysis revealed that critically ill COVID-19 during the acute phase (aOR=3.35, 95% CI: 1.48-7.62, P < 0.001) and presence of long COVID-19 syndrome postoperatively (aOR=2.50, 95% CI: 1.90-3.29, P < 0.001) were associated with CPSP.  Conclusions  It is clear for the first time that critically ill COVID-19 during the acute phase and the presence of long COVID-19 syndrome postoperatively are the risk factors for CPSP among patients with preoperative COVID-19.

Objective:To understand the epidemiological characteristics of human parainfluenza viruses（HPIVs）infections in patients with acute lower respiratory tract infection（ALRTI）in Changsha，Hunan from 2013 to 2023.Methods:The respiratory virus detection results,demographic characteristics and clinical data of children hospitalized with ALRTI in Children's Medical Center of Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2013 to December 2023 were retrospectively collected.The epidemic characteristics and clinical symptoms of HPIVs infection were analyzed.Results:During the study,59 725 children with ALRTI were included,the detection rate of HPIVs was 6.66% (3 978/59 725),among which,HPIV1,HPIV2,HPIV3 were detected in 753(1.26%) cases,217(0.36%) cases and 3 055(5.12%) cases,respectively.Among 3 978 cases infected with HPIVs,the overall detection rate in males was higher than that in females(6.99% vs. 6.14%),and the detection rate of HPIVs in 6-11 months old was higher than those in other age groups,with statistically significant differences( P<0.001).Among cases infected with HPIVs,the main clinical diagnosis were mild pneumonia (77.28%) and acute bronchiolitis (14.40%).The detection rate of HPIV3 was the highest (84.62%) in 208 HPIVs-positive children with severe pneumonia,and the difference was statistically significant ( P<0.001).The detection rate of HPIVs varied across different years,reaching its peak in 2020 with a detection rate of 13.99% ( P<0.001).The overall epidemic peak of HPIVs was in spring and summer.The seasonal epidemic characteristics in different types of HPIVs were not completely consistent.The detection rates of HPIV1(2.07%) and HPIV2(0.60%) were the highest in autumn,while that of HPIV3 (7.11%) was the highest in spring ( P<0.001).The seasonal epidemic characteristics of HPIVs have changed in different years:From 2013 to 2019,HPIVs was mainly prevalent in spring and summer,then shifted to summer and autumn in 2020,and autumn as well as winter in 2021 to 2022,then resumed in spring and summer in 2023. Conclusion:From 2013 to 2023,HPIVs in Changsha,Hunan Province had unique epidemiological characteristics.HPIV3 is the dominant type of HPIVs infection in the hospitalized children with ALRTI in Changsha，Hunan.The epidemic peak of HPIVs was postponed in 2020 to 2022.Paying attention to the continuous monitoring of HPIVs infection is helpful to guide clinicians' diagnosis and treatment.