Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:Clinical characteristics and diagnosis and treatment process was reported and analyzed of a patient with brucellosis complicated with thyroid abscess, providing reference for the clinical diagnosis of brucellosis complicated with thyroid abscess.Methods:Clinical medical records of a patient with brucellosis complicated with thyroid abscess who was treated at the General Surgery Department of Yanchi County People's Hospital in Wuzhong City, Ningxia Hui Autonomous Region in November 2021 were collected. The clinical manifestations, blood routine, brucella antibodies, thyroid function, bacterial culture, thyroid ultrasound and other examination results, as well as the diagnosis and treatment process, were comprehensively analyzed. Results:The patient was a male, 61 years old, who presented with a neck mass without typical clinical manifestations of brucellosis. Thyroid ultrasound revealed a space occupying lesion, and the preliminary diagnosis was thyroid cystadenoma. Thyroid right lobe and isthmus resection surgery was performed. During the operation, it was found that some of the thyroid glands were tightly adhered to the cervical blood vessels, so the resection surgery was changed to abscess drainage, and the drainage fluid was purulent and bloody. The bacterial culture result of thyroid purulent fluid (intraoperative puncture fluid and postoperative drainage fluid) was brucella lamblia, and the serum brucella test tube agglutination test titer was 1 ∶ 400 (+++). The patient improved and was discharged after local drainage and anti brucella treatment. Follow up for 4 months showed no abnormalities. Conclusions:Brucellosis which begins with a local infection of the thyroid gland is extremely rare, with no characteristic clinical manifestations, and is prone to misdiagnosis. Timely correction of the surgical plan during the treatment process avoids the removal of the patient's thyroid, which has a certain clinical reference value.

Objective:To retrieve and summarize the best evidence on non-pharmacological interventions for pain management in knee osteoarthritis.Methods:The literatures related to non-pharmacological intervention in pain management for knee osteoarthritis were searched on UpToDate, BMJ Best Practice, Australia Joanna Briggs Institute evidence-based healthcare center database, Cochrane Library, National Institute for Health and Clinical Excellence, Guidelines International Network, Medlive, Medline, PubMed, Wanfang database and China National Knowledge Infrasructure. The evidences were extracted after quality evaluation of the included literature.Results:A total of 11 references were included, including 6 guidelines, 2 expert consensuses, 2 systematic evaluations and 1 randomized controlled trial. Finally, 22 pieces of best evidences were summarized from 6 aspects, including health education, pain assessment, referral, psychological intervention, exercise intervention and physical therapy.Conclusions:Summary of the best evidence for non-pharmacological intervention in pain management for patients with knee osteoarthritis can provide evidence-based evidence for clinical healthcare professionals and knee osteoarthritis patients to undergo non-pharmacological pain intervention.

Objective To analyze the reason of drug shortages in medical institutions and take corresponding prevention measures to ensure drug supply .Methods The drug outbound orders in 2012 were retrospectively analyzed to trace the pro‐curement plan of badly‐needed drugs and the delivery time of supplier .Excel was used to carry out classification and statistics for the information of drug shortages combined with the explanations that the supplier failed to supply to summarize the exter‐nal cause and internal cause of drug shortages in medical institutions .Results In 2012 ,the dispensing department received a to‐tal of 46862 plans ,and 1423 items were badly‐needed drugs .The drug shortage rate was 3 .0% .643 times of drug shortages were caused by external causes which accountedfor 45 .2% of all the shortages ;780 times of the drug shortages were caused by internal causes which accounted for 54 .8% .Price inversion accounted for 40 .7% in the external causes that lead to the drug shortages ,and it was the top of the external causes for drug shortages .The low‐priced small varieties and generic drugs ac‐counted for 71 .2% of drug shortages caused by external causes;in the internal causes of drug shortages ,the inventory control accounted for 45 .0% ,ranked the first .Conclusion The scientific and reasonable drug price ,the improvement of bidding poli‐cy ,the joint effort of all parties of drug supply chain ,and the enhancement of the early warning and management of the badly‐needed drugs can reduce drug shortage .

Objective To provide better emergency and patient services in well-equipped comprehensive hospitals, the organization and wisdom therapeutic strategy are of great importance for the recovery of injured patients from the earthquake zone. Method From 12 May 2008, following the 8.0 Magnitude earthquake in Wenchuan county of Sichuan Province, six Chongqing hospitals with third class in grade A were involved in the rescue of the injured patients with great effort. A total of 533 patients were retreated and followed up from quake zone. All the patients were scored with ISS and AIS system. The profiles of the patients examined, operated and clinical infection investigation were documented. Results Of 533 patients, the number of the patients whose ISS is below 16 is 456 (83.6%), the number between 16 and 25 is 65 (12.2%), and the humor above 25 is 12 (2.3%). The patients were classfled based on their fracture parts as follows: head and neck (n = 42), face (n = 7), chest (n = 114), abdominal and cavitas pelvis (n =81), limb and pelvis (n =314), body surface (n =205), with 180 single fracture site, 139 of them being two combined fracture sites, and 114 of them being above three combined fracture sites. Thirty-two of the patients were suffered from amputation. The number of patients suffered from crushing syndrome reached 21, with 281 surgical operations in hospitals. Seventy-nine patients were suffered from infections including 87.3% of pre-hespital infections. The results from bacteria culture and antibiotic susceptibility showed that the infected bacteria mainly involved in Escherichia coli, Staphylococcus anreus, Staphylococcus haemolyticns, Klebsiella pneumoniae, Baumanii, Aerobacter cloacae, Pseudomonas aeruginosa, C type chain coccus, Bacillus aerogenes capsulatus. The antibiotic susceptibility to diverse bacteria has no obvious changes and exists partial overlapping, and infected patients should be given the treatment of cephalosporin, macrolide antibiotic and so on. Conclusions For the emergency conditions after the catastrophe, the comprehensive hospitals must be prepared to meet large quantities of severe trauma and infection therapy. The scientific selection of antibiotics in the combinative therapy is of great importance to the enhancement of early specific treatment, prevention of severe trauma complications and rehabilitation of patients.

Objective To investigate the predisposing factors of urinary tract infection(UTI) with extendedspectrum beta-lactaraase(ESBLs) producing Escherichia Coli(E. coli) and its resistance to antimicrobial agents.Methods 26 cases of UTI patients with ESBLs producing E. coli from 2003 to 2005 in our hospital were analyzed retrospectively and compared with the ESBLs non-producing strains. Results 88.5 % of the patients with UTI in ESBLs producing E. coli had received broad-spectrum antimierobial therapy before the diagnosis, 69.2 % of the patients were complicate UTIS, 42.3 % of the patients experienced invasive operations in urinary tract; the incidence of drug resistance of ESBLs producing bacteria to the second, third-generation cephalosporins and quinolone was significantly higher than that of ESBLs non-producing bacteria, but it was highly sensitive to imipenem. Conclusion The drug resistance of ESBLs producing E. coli is severe gradually. So much attention should be paid to the ESBLs producing bacteria detection in UTIs. Antimicrobial therapy should be initiated under the guidance of drug sensitivity test,it is necessary to rid the predisposing factors of UITs as much as possible in order to decrease ESBLs-producing bacteria infection.

BACKGROUND: The activation of hypothalamus-pituitary-adrenal cortex axis may play key role in the increasing expression of hypothalamic corticotropin-re-leasing hormone (CRH) during stress reaction. However by what way to induce the CRH expression in hypothalamic neuron, and whether CRH can activate hypothalamic neurons are still not very clear.OBJECTIVE: To observe the changes of intracellular cyclic adenosine monophosphate (cAMP) and cytoplasmic Ca2+ concentration in the hypothalamic neurons cultured in vitro due to exogenous CRH stimulation.DESIGN: Comparative observation experiment.SETTING: Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA; Department of Neurosurgery , Tiantan Hospital, Capital University of Medical Sciences MATERIALS: This experiment was carried out in the Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA between December 1999 and March 2002. Hypothalamus was obtained from fetus rat at pregnancy of 17 days for the in vitro culture of hypothalamic neurons.METHODS: Hypothalamic neurons were co-cultured with exogenous CRH,with or without pretreatment with specific CRH 1 receptor antagonist -CP-154526. hypothalamic neurons were randomized into: ① CRH (10-12,10-10, 10-8, 10-6 mol/L) stimulation group. ② CP-154526(500 μmol/L)pretreatment aud CRH ( 10-12, 10-10, 10-8,10-6 mol/L) stimulation group. ③Hypothalamic neurons in corresponding normal control group were exposed to the isotonic saline stimulation. PTI fluorescence image system was used to determine and analyze the change of cytoplasmic free Ca2+ concentration in hypothalamic neurons due to exogenous CRH stimulation and RIA was used to detect the neuronal cAMP content.MAIN OUTCOME MEASURES: ①Cytoplasmic free Ca2+ concentration in hypothalamic neurons. ②cAMP content in hypothalamic neurons.RESULTS: The cytoplasmic free Ca2+ concentration and cAMP content were relatively lower in the hypothalamic neurons in normal control group,which obviously increased due to CRH stimulation [(240±22),(153±11)nmol/L; (3.26±0.19),(0.44±0.02) pmol/dish,P ＜ 0.01];CP-154526 could remarkably suppress the CRH (10-6 mol/L)induced increase in cytoplasmic free Ca2+ concentration and cAMP content in hypothalamic neurons [Ca2+ concentration: (240±22),(171±16)nmol/L; cAMP content:(3.26±0.19), (2.33±0.21) pmol/dish, P ＜ 0.01].CONCLUSION: CRH can directly act on hypothalamic neurons via type 1-receptor,thereby increase the cytoplasmic free Ca2+ concentration and cAMP content in hypothalamic neurons,playing the key role in the modulation of the synthesis and secretion of CRH during the activation of hypothalamic neurons.

OBJECTIVE To explore the characteristics of cochlear hair cell injuries in guinea pigs exposed to blast underpressure(BUP). METHODS The guinea pigs were killed 14 days after exposure to experimental BUP. Their basilar membranes were stained by silver nitrate and the hair cell injuries were quantitatively assessed using the light microscope. RESULTS The outer hair cells(OHCs) of the guinea pigs clearly appeared to be injured following exposure to the experimental BUP at a peak underpressure varying between -22.4kPa and -63.3kPa. The most obvious injury was in the second turn and OHC loss was smallest in the first row and more severe in the second and third rows. OHC loss was seen in all of three experimental groups of animals following exposure to BUP. Furthermore, the higher the peak of underpressure, the more obvious the injury of OHCs. Quantitative morphological analysis of cochlear hair cells showed that the total OHC loss rates in all the experimental groups of guinea pigs exposed to BUP were significantly higher than that of control group animals(P

BACKGROUND: Through what signal pathway does corticotropin release hormone (CRH) regulate hypothalamic neuronal neuroendocrine activity during acute stress?OBJECTIVE: To probe into the regulatory effects of CRH on CREB secretion in hypothalamic neurons.DESIGN: Repetitive measurement design.SETTING: At Field Surgery Research Institute of Daping Hospital, Third Military Medical University of Chinese PLA; Neurosurgery Department,Tiantan Hospital Affiliated to the Capital University of Medical Sciences.MATERIALS: This experiment was carried out in Daping Hospital of Third Military Medical University of Chinese PLA between December 1999and March 2002. Rat fetuses were selected from Wister rats of 17-day gestation.METHODS: In vitro cultured cells were divided into the following groups:① CRH (10-12, 10-10, 10-8 and 10-6 mol/L) stimulation groups. ② Pretreated with nimodipine (5 μmol/L) or CP-154526 (500 μmol/L) followed by CRH (10-12, 10-10, 10-8 and 10-6 mol/L ) stimulation groups. ③ Corresponding control groups stimulated with isotonic physiological saline. PTI fluorescence imaging system was used to detect the changes of neuronal cytoplasmic free calcium concentration; meanwhile, Western blot technique was used to determine the changes of neuronal P-CREB content.MAIN OUTCOME MEASURES: ① Changes of neuronal cytoplasmic free calcium concentration. ② Changes of neuronal P-CREB content.RESULTS: The content of cytoplasmic free calcium in hypothalamic neurons was lower in normal control group, and it increased immediately after exogenous CRH stimulation. However, such increase could be suppressed by pretreatment with nimodipine or CP-154526 before CRH stimulation,and the increase of neuronal P-CREB content was also obviously suppressed.CONCLUSION: During acute stress, the combination of CRH with hypothalamic neuronal CRH 1 receptor leads to the opening of membrane Ltype calcium ions channels, thus enhancing the influx of calcium ions and increasing cytoplasmic free calcium ions content, which would further activate P-CREB signal transduction pathway in neurons. It suggests that CRH may play a vital role in hypothalamic neuronal activation.