Objective To compare the differences in virulence-related factor aspartate protease,biofilm formation,and gene expression among clinical isolates of Candida parapsilosis(C.parapsilosis).Methods Gene sequencing and microsatellite typing(MT)method were adopted to identify C.parapsilosis isolated from patients with clinical fungal infection.The production of secreted aspartate protease and biofilm formation ability of each strain were de-tected,and the expression of biofilm formation related-genes BCR1,EFG1,and HWP1,as well as aspartate prote-ase virulence genes SAPP1,SAPP2,SAPP3 were compared among the strains.Results A total of 8 clinically iso-lated C.parapsilosis strains were collected,all of which were identified as genotype Ⅰ.Based on microsatellite ty-ping results,8 clinical strains were divided into 4 microsatellite types.G1,G2,and G3 strains isolated from the urine,peripherally inserted central catheters(PICC),and blood of patient A were of different subtypes.J1,J2,J3,J4,and J5 strains were of the same type,and isolated from blood specimens of patient B at different periods.All 8 clinical strains could form biofilm,and their biofilm formation ability was higher than that of the standard strain of C.parapsilosis(ATCC 22019).G1,G3 and J5 strains had strong biofilm formation ability,J1,J2,J3,and J4 strains had moderate biofilm formation ability,and G2 strain had weak biofilm formation ability.All of the eight clinical isolates secreted aspartate protease,and their in vitro expression levels of the enzyme were higher than that of the standard strain(ATCC 22019).G3,G1,and G2 strains showed low,moderate,and high in vitro enzyme expression respectively,with statistical differences(all P＜0.05).Enzyme expressed moderately in J1 and J5 strains,and highly in J2,J3,and J4 strains.Difference between moderate and high expressions was statistically significant(P＜0.05).The expression levels of biofilm formation genes BCR1,EFG1,and HWP1 in various strains isolated from patients A and B increased.In strains isolated from patient A,the expression level of EFG1 gene in G1 strain was higher than that in G2 strain(P＜0.05).There was no statistically significant difference in BCR1,EFG1,and HWP1 gene expression levels among strains isolated from patient B.The expression levels of as-partate protein genes(SAPP1,SAPP2,and SAPP3)in various strains isolated from patients A and B increased.The expression levels of SAPP1 and SAPP2 in strain G1 were higher than those in G2 and G3(both P＜0.05).There was no statistically significant difference in the expression levels of SAPP1,SAPP2,and SAPP3 genes in strains from patient B.Conclusion Clinical isolates of C.parapsilosis have higher biofilm formation and aspartate protease production abilities than standard strain.The expression of virulence factors varies among strains isolated from different specimens,while there is no significant difference in the expression of virulence factors among strains isolated at different periods.Patients may have been infected with different MT types of C.parapsilosis in multiple sites during the same period.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

Abstract: Objective　To analyze the emergency response and long-term intervention effects after the detection of infectious snails epidemic by loop-mediated isothermal amplification (LAMP) assays in Hannan District, Wuhan City, and to explore the application of LAMP in early surveillance and early-warning of schistosomiasis transmission. Methods Snails picked up by the risk monitoring system in Hannan District were examined by anatomical microscopy and LAMP technology to identify the schistosomiasis infection. Emergency response and intensive intervention were initiated in the environment where positive snails appeared, and the long-term effects were evaluated. Results In May 2018, the infectious snails were detected by LAMP technology in Hannan District, and the positive snails were located in Zhujiacha, Dongzhuang Village, Obstacles and weeds were removed and buried by machine in Zhujiacha. 12 700 m2 of snails were killed by drugs, and the mortality rate of snails was more than 80%; no new seropositive persons were found in the emergency examination within 500 m of the positive snail sites. 506 people were examined in Dong Zhuang Village at the end of the year, and 30 positive IHA cases were detected with a blood positive rate of 5.93%, no positive fecal test was found, and all positive blood test patients took preventive medication. The monitoring results of sentinel rats and wild feces were all negative. Health education was carried out, 7 warning signs were deployed and refreshed, and 500 publicity brochures were distributed. After nearly three years of intensified intervention and monitoring in the villages where the positive environment is located, and the density of snails on the stubborn snail has dropped from 0.094/frame to 0.027/frame, and the positive rate of blood test in Dongzhuang Village has steadily dropped from 5.93% to 3.74%. Conclusions The infected snails missed by microscopy were detected by LAMP in Hannan District, which created conditions for the rapid emergency treatment of environment and elimination of positive snail and improved the sensitivity of the surveillance and early warning system in transmission-interrupted areas.

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.
United States ; Humans ; Ischemic Stroke ; C-Reactive Protein ; Acupuncture Therapy ; Inflammation ; Homocysteine ; Hypersensitivity ; Thrombolytic Therapy

Objective: To explore the application effects of bundle nursing of citric acid extracorporeal anticoagulation on continuous renal replacement therapy (CRRT) of severe burn patients. Methods: A non-randomized controlled study was conducted. Forty-six patients who met the inclusion criteria and received regular nursing of citric acid extracorporeal anticoagulation during CRRT in the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from January to December 2017 were included in regular nursing group (30 males and 16 females, aged 42.0 (38.7,47.0) years, with 201 times of CRRT performed), and 48 patients who met the inclusion criteria and received bundle nursing of citric acid extracorporeal anticoagulation during CRRT in the same hospital from January to December 2018 were included in bundle nursing group (32 males and 16 females, aged 41.0 (36.0,46.0) years, with 164 times of CRRT performed). The clinical data of all the patients in the two groups were recorded, including the length of intensive care unit (ICU) stay, total cost of treatment in ICU, cost of CRRT, unplanned ending of treatment, ending of treatment due to operation (with the rates of unplanned ending of treatment and ending of treatment due to operation calculated), times of disposable hemodialysis filter and supporting pipeline filter (hereinafter referred to as filter) with use time>24 h, times of CRRT, and lifetime of filter. For the patients in both groups who continuously received CRRT for 3 days or more from the first treatment, the prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), total calcium, ionic calcium (with the difference of total calcium or ionic calcium between before and after treatment calculated), creatinine, urea, β₂ microglobulin, cystatin C, platelet count, mean arterial pressure, pH value, oxygenation index, bicarbonate radical, and lactic acid levels before the first treatment (hereinafter referred to as before treatment) and 3 days after the first treatment (hereinafter referred to as after 3 days of treatment). The treatment-related complications of all patients in the two groups were recorded during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. Results: Compared with those in regular nursing group, the length of ICU stay was significantly shortened (Z=-4.71, P<0.01), the total cost of treatment in ICU was significantly reduced (t=-1.39, P<0.01), the cost of CRRT had no significant change (P>0.05), the rates of unplanned ending of treatment and ending of treatment due to operation were both significantly decreased (with χ² values of 12.20 and 17.83, respectively, P<0.01), the times of filter service time>24 h was increased significantly (Z=-5.93, P<0.01), the times of CRRT were significantly reduced (Z=-4.75, P<0.01), and the filter service life was significantly prolonged (Z=-9.24, P<0.01) among patients in bundle nursing group. Thirty-one patients in bundle nursing group and 28 patients in regular nursing group continuously received CRRT for 3 days or more from the first treatment. Before treatment, PT, APTT, and INR of patients in bundle nursing group were 24.10 (16.08, 39.20) s, 38.81 (32.32, 45.50) s, and 1.17 (1.12, 1.19), respectively, similar to 31.75 (22.99, 40.96) s, 41.82 (35.05, 48.06) s, and 1.15 (1.11, 1.19) of patients in regular nursing group (P>0.05); the levels of total calcium and ionic calcium of patients in the two groups were similar (P>0.05). After 3 days of treatment, PT, APTT, and INR of patients in bundle nursing group and regular nursing group were 29.06 (20.11, 39.46) s, 35.25 (30.06, 40.28) s, 1.13 (1.09, 1.17) and 36.51 (26.64, 42.92) s, 39.89 (34.81, 46.62) s, 1.14 (1.10, 1.18), respectively, similar to those before treatment (P>0.05); the level of ionic calcium of patients in regular nursing group was significantly higher than that before treatment (Z=-2.08, P<0.05); the levels of total calcium and ionic calcium of patients in bundle nursing group were both significantly higher than those before treatment (with Z values of -3.55 and -3.69, respectively, P<0.01); compared with those in regular nursing group, APTT of patients was significantly shorter (Z=-2.29, P<0.05), while the total calcium level of patients was significantly higher in bundle nursing group (Z=-2.26, P<0.05). The difference of total calcium between before and after treatment of patients in bundle nursing group was significantly higher than that in regular nursing group (Z=-3.15, P<0.01). The differences of ionic calcium between before and after treatment of patients in the two groups were similar (P>0.05). Before treatment, the level of β₂ microglobulin of patients in bundle nursing group was significantly higher than that in regular nursing group (Z=-2.84, P<0.01), the platelet count of patients in bundle nursing group was significantly lower than that in regular nursing group (Z=-2.44, P<0.05), while the levels of creatinine, urea, cystatin C, mean arterial pressure, pH value, oxygenation index, bicarbonate radical, and lactic acid of patients in the two groups were similar (P>0.05). After 3 days of treatment, the levels of creatinine, urea, β₂ microglobulin, cystatin C, pH value, bicarbonate radical, and lactic acid of patients were all significantly lower than those before treatment (with Z values of -2.10, -2.90, -3.11, -2.02, -2.34, -2.63, and -2.84, respectively, P<0.05 or P<0.01), while the levels of platelet count, oxygenation index, and mean arterial pressure of patients were all significantly higher than those before treatment in bundle nursing group (with Z values of -6.65 and -2.40, respectively, t=-9.97, P<0.05 or P<0.01); the levels of creatinine, urea, β₂ microglobulin, cystatin C, platelet count, pH value, bicarbonate radical, and lactic acid of patients were all significantly lower than those before treatment (with Z values of -5.32, -2.31, -2.41, -2.21, -3.68, -2.93, -2.20, and -2.31, respectively, P<0.05 or P<0.01), while the oxygenation index and mean arterial pressure of patients were both significantly higher than those before treatment in regular nursing group (Z=-5.59, t=-7.74, P<0.01). After 3 days of treatment, compared with those in regular nursing group, the levels of creatinine, cystatin C, platelet count, oxygenation index, bicarbonate radical, and mean arterial pressure of patients were all significantly higher (with Z values of -2.93, -1.99, -6.39, -2.09, and -2.52, respectively, t=-3.28, P<0.05 or P<0.01), while the levels of urea, β₂ microglobulin, pH value, and lactic acid of patients were all significantly lower (with Z values of -3.87, -2.58, -4.24, and -2.75, respectively, P<0.05 or P<0.01) in bundle nursing group. During hospitalization, there were no treatment-related bleeding events or hypernatremia related to citric acid treatment of patients in the two groups. The ratio of total calcium to ionic calcium in one patient in bundle nursing group was >2.5, but there was no manifestation of citric acid accumulation poisoning; 1 patient had hypoionic calcemia, and 1 patient had severe metabolic alkalosis. Five patients had hypoionic calcemia and 2 patients had severe metabolic alkalosis in regular nursing group. Conclusions: The implementation of bundle nursing of citric acid extracorporeal anticoagulation during CRRT for severe burn patients shortens the length of ICU stay, reduces the total cost of treatment in ICU and the occurrence of treatment-related complications, relieves the economic burden of patients, and improves the continuity and quality of treatment.
Adult ; Anticoagulants ; Burns/therapy* ; Citric Acid ; Continuous Renal Replacement Therapy ; Female ; Humans ; Male ; Retrospective Studies

Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.