Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

OBJECTIVE: To investigate the clinical and genetic characteristics of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) due to variant of WASF1 gene, and to review the literature on NEDALVS associated with WASF1 gene variants. METHODS: A 4-year-and-8-month-old boy with NEDALVS diagnosed at Linyi People's Hospital in July 2024 due to "discovering language development delay for more than 2 years" and his family members were selected as the study subjects. Clinical data of the family members were collected. Peripheral venous blood samples were collected from family members. Whole-exome sequencing (WES) was performed, and candidate variants were verified, by Sanger sequencing. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Using the MUpro website, SWISS-MODEL, PyMOL, Clustal X, PolyPhen-2, and Mutation Taster software, bioinformatics analysis of protein three-dimensional structure modeling for gene mutations, cross-species conservation of mutant amino acids, and pathogenicity prediction of mutation sites. Relevant literature was retrieved from databases such as CNKI, Wanfang Data Knowledge Service Platform, and PubMed, and the clinical phenotypes and genotypes of patients with WASF1 gene mutations reported in the literature were summarized and analyzed. This study was approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: YX200303). RESULTS: The proband, a 4-year and 8-month-old male, mainly presented with delayed language and motor development, accompanied by autistic behaviors; the proband's younger brother was 2 years and 7 months old at the time of consultation, mainly presented with delayed language and motor development, accompanied by short stature; the proband's mother mainly presents with limited language expression and poor interpersonal interaction; the proband's maternal grandmother mainly presents with soliloquizing?behavior. The results of WES showed that the proband carried a heterozygous mutation c.214C>T (p.Arg72Cys) in the WASF1 gene, and this site has not been recorded in the database. Sanger sequencing confirmed that the proband's younger brother, mother, and maternal grandmother had harbored the same variant. Based on the guidelines from the ACMG, this variant was rated as likely pathogenic (PM2_Supporting+PP1+PP3+PP4). Through SWISS-MODEL homology modeling and PyMOL structure visualization analysis, it was further confirmed that this variant can lead to a decrease in protein stability. Amino acid sequence conservation analysis of the WASF1 protein using Clustal X software suggested that the c.214C>T (p.Arg72Cys) variant has caused replacement of a highly conserved amino acid. According to the results of PolyPhen-2 and Mutation Taster, the p.Arg72Cys variant was predicted to be a hazardous. By following the retrieval strategy set in this study, a total of 5 research articles regarding to patients with NEDALVS caused by WASF1 gene mutations were retrieved, which involved 15 patients. Combining the proband and their family members discovered in this study, there were a total of 19 NEDALVS patients. The main clinical features included: motor developmental delay (100%, 17/17), language/intellectual developmental delay (100%, 17/17), epilepsy (64.7%, 11/17), autistic behavior (76.5%, 13/17), hypotonia (70.6%, 12/17), abnormal electroencephalogram (64.7%, 11/17), and short stature (17.6%, 3/17). All 19 patients had heterozygous mutations, with 8 mutation sites. Missense mutations were the most common, accounting for 84.2% (16/19). CONCLUSION A pathogenic variant of the WASF1 gene was identified in a pedigree affected with NEDALVS. Discovery of the novel variant has, expanded the mutational spectrum of the WASF1 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; China ; Exome Sequencing ; Mutation ; Neurodevelopmental Disorders/genetics* ; Pedigree ; Seizures/genetics* ; East Asian People/genetics*

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

The construction of smart hospital is an important part of modern hospital management system,and it is also the key way to build the new system of high-quality hospital development.In terms of building smart hospitals,multi-campus hos-pitals face more difficulties and challenges than single campus hospitals,such as the lack of top-level design,the difficulty of in-tegrated management,the uneven development of hospitals and the widespread phenomenon of information islands.This study summarizes and analyzes the difficulties encountered in the construction and application of smart hospitals in multi-hospital areas.Guided by problems,it puts forward countermeasures and suggestions for the construction of refined and high-quality smart hospi-tals in multi-campus hospitals,including strengthening overall and forward-looking awareness,integrating management according to hospital conditions,characteristic development under demand guidance,establishing a data integration center for smart hospi-tals,scientific planning of talent reserve and discipline layout,etc.

Objective To explore the application of nucleic acid test in the diagnosis of HIV western blotting (WB) indeterminate and negative samples. Methods A total of 2 518 HIV samples to be confirmed were collected from the Hubei HIV Confirmation Center Laboratory from 2014 to 2022. The results of follow-up antibody test and nucleic acid test of WB indeterminate and negative samples were analyzed, and the diagnostic rate, sensitivity, specificity and coincidence rate of the two detection strategies were compared. Results There were totally 133 indeterminate or negative samples by WB test. Of the 99 indeterminate samples , 76 (76.77%) had nucleic acid test results >5000 copies/mL. 40 cases were followed up, of which 33 cases (82.50%) turned positive and 7 (17.50%) were still uncertain. Of the 7 samples with 20~5000 copies /mL (7.07%), 2 cases were followed up and both turned positive during the follow-up. 1 case (1.01%) with nucleic acid <20 copies/mL turned positive during follow-up. Among the 34 WB negative samples, 15 cases (45.45%) were > 5 000 copies/mL, 9 of which were seroconversion. The diagnostic rates of ^“antibody confirmation^” and ^“nucleic acid test^” were 96.78% (2 437/2 518) and 99.60% (2 508/2 518), respectively. The sensitivities were 98.02% (2 430/2 479) and 99.88% (2476/2 479), and the specificities were 78.13% (25/32) and 100.00 % (32/32), respectively. The coincidence rates were 97.77% (2 455/2 511) and 99.88% (2 508/2 511), respectively. Conclusion Nucleic acid supplemental test strategy has high diagnostic rate, sensitivity, specificity and coincidence rate. WB indeterminate and negative samples can be diagnosed as early as possible through nucleic acid supplemental testing.

Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.

Surgery for periprosthetic fractures (PPF) is one of the most complex procedures in orthopedics. It is difficult, highly risky and extremely challenging, because the patients are usually advanced in age and suffering from essential organ dysfunction, numerous comorbidities, poor overall body condition, poor bone quality combined with osteolysis and even bone loss, and because the surgeons have to apply the concepts and techniques of Modern Orthopedic Trauma and artificial joint revision techniques in fracture fixation and prosthesis revision. This paper expounds on the clinical challenges due to the characteristics of PPF in order to call on clinical surgeons to update their concepts, deal with seriously and standardize their PPF treatment, and effectively improve their efficacy.

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.