In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

This report describes two cases of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with umbilical cord mesenchymal stem cells (UC-MSCs). Case 1 was a child with severe aplastic anemia who underwent haploidentical bone marrow and peripheral blood HSCT, with a chimerism rate of 99.8% on day +25 and severe immune-mediated thrombocytopenia on day +60. After intravenous immunoglobulin (IVIG) pulse therapy, platelet count increased temporarily but then decreased, while cyclosporine, methylprednisolone, and rituximab had a poor therapeutic effect. Case 2 was a child with Gaucher's disease who underwent unrelated umbilical cord blood HSCT, with a chimerism rate of 96.35% on day +41 and severe immune-mediated thrombocytopenia on day +153. After three sessions of IVIG pulse therapy, the platelet count increased initially but subsequently decreased. Therapies with dexamethasone, prednisone, cyclosporine, and recombinant human thrombopoietin also yielded a poor response. Both children received three sessions of UC-MSCs infusion, and platelet counts increased and were subsequently maintained within the normal range. Case 1 has been followed up for 10 years and remains in disease-free survival. UC-MSCs infusion may be effective for severe immune-mediated thrombocytopenia that is unresponsive to first- and second-line therapies after HSCT and could potentially improve the quality of life and disease-free survival rate.
Child ; Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Thrombocytopenia/therapy* ; Transplantation, Homologous ; Umbilical Cord/cytology*

OBJECTIVE Aimed at investigating whether reflux pharyngitis is an independent risk factor for the failure of type Ⅰ tympanoplasty for chronic otitis media.This is achieved by analyzing the relationship between the postoperative tympanic membrane healing in patients who underwent type Ⅰ tympanoplasty and pharyngolaryngeal reflux finding score(RFS).METHODS Patients who underwent type Ⅰ tympanoplasty in the Department of Otolaryngology Head and Neck Surgery,Nanshan People's Hospital,Shenzhen,China,from January 2023 to July 2024 were retrospectively included.All the patients received preoperative perfect nasal endoscopy,laryngoscopy,evaluation by the RFS questionnaire,preoperative otoscopy for tympanoplasty,pure tone hearing threshold,and temporal bone thin-layer CT examination.Postoperative otoscopic examination was performed to observe tympanic membrane healing and followed up for 3 months.The patients were divided into surgery success group and failure group based on the criterion of whether a complete tympanic membrane was formed by endoscopic examination within 3 months.The RFS scores of the two groups were statistically analyzed.RESULTS A total of 135 patients with an average age of 44.78 years(±12.22 years)took part in this study,with 60 males and 75 females included,and 68 left ears and 67 right ears involved.There were 120 patients in the surgery success group,and 15 patients in the failure group.Statistical analysis revealed that the RFS score of the patients in the tympanoplasty failure group was remarkably higher than that of the patients in the tympanoplasty success group.Moreover,there were significantly more cases with suspected reflux pharyngitis in the surgery failure group(P=0.007).Reflux-induced tympanic membrane lesion and reperforation mostly occurred in the central part of the tympanic membrane graft.CONCLUSION Reflux pharyngitis has been implicated with tympanoplasty failure,and thus may be a causative factor.Additionally,the RFS can be used to screen patients with chronic suppurative otitis media for suspected reflux pharyngitis.Findings from this work indicate that perioperative anti-reflux therapy,combined with dietary and lifestyle counselling for the patients who suffer from reflux pharyngitis and are about to undergo the tympanoplasty surgery may improve surgical success rate.

Hepatic ascites is one of the common and difficult complications in the decompensated stage of liver cirrhosis， and its incidence is increasing. In clinical practice， the prognosis of patients with hepatic ascites after surgery is worse， and the disease is recurrent. Traditional Chinese medicine （TCM） has certain advantages in treating hepatic ascites. However， there is no uniform standard for the preparation of animal models of hepatic ascites in accordance with TCM evidence. Therefore， this paper summarized the literature on animal models of hepatic ascites and analyzed the existing animal models of hepatic ascites based on the clinical diagnostic criteria of hepatic ascites in TCM and western medicine. The results show that the commonly used modeling methods for hepatic ascites mainly include the single-factor method， composite factor induction method， surgical method， and immunization method. Most of them are guided by western medicine theories， and their pathogenic mechanisms are mostly consistent with those of western medicine and are different from TCM evidence. Therefore， it is suggested that TCM intervening factors should be imposed in the process of model preparation， so as to prepare an animal model of hepatic ascites that meets the clinical evidence characteristics of TCM and western medicine.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To explore the clinical correlation and prognostic value of the Albumin-Bilirubin(ALBI)score in children with secondary hemophagocytic syndrome(sHLH).Methods:A retrospective analysis was conducted on the data of children's sHLH cases clearly diagnosed in the Affiliated Hospital of Zunyi Medical University from January 2012 to March 2023.Survival analysis was conducted according to the ALBI classification.Spearman correlation analysis was conducted between the ALBI score and clinical indicators.The Receiver Operating Characteristic(ROC)curve was used to evaluate the ALBI score,select the best cutoff value,and evaluate the accuracy of prognostic prediction value.Kaplan-Meier method was used to draw the survival curve.Log-rank method was used to compare the differences of survival curve between groups.Cox regression was used for prognostic analysis and restricted cubic spline curves used to calculate the relationship between ALBI scores and the risk of death in children with sHLH.Results:A total of 128 children with sHLH were included in this study,with a median age of 38(13.25,84)months.There were 70 males(54.69％)and 58 females(45.31％).The survival analysis results of ALBI grading showed that the survival rate of HLH patients with ALBI grade 3 was significantly lower than those with ALBI grades 1 and 2.Spearman correlation analysis results showed that ALBI score was positively correlated with splenomegaly,respiratory failure,disseminated intravascular coagulation(DIC),pulmonary hemorrhage,gastrointestinal hemorrhage,central nervous system involvement,ALT,AST,TG,LDH,PT,APTT,and SF(the correlation coefficients are:r=0.181,0.362,0.332,0.221,0.351,0.347,0.391,0.563,0.180,0.448,0.483,0.37,0.356),and was negatively correlated with HB,PLT,and FIB(the correlation coefficients are:r=-0.321,-0.316,-0.423),but was not significantly correlated with EBV infection,fungal infection,hepatomegaly,and ANC(P＞0.05).Using the ROC curve,the cutoff value of ALBI was-1.76.Single factor Cox regression analysis results showed that HB＜90 g/L,ALT ≥ 80 U/L,AST≥200 U/L,LDH ≥1 000 U/L,PT ≥20 s,APTT≥40 s,FIB＜1.5 g/L,ALBI ≥-1.76,combined pulmonary hemorrhage,DIC,central nervous system involvement,gastrointestinal bleeding,and not using blood purification may be the prognostic risk factors for children with sHLH(P＜0.05).Multivariate Cox regression results showed that FIB＜1.5 g/L(HR=2.119,95％CI:1.028-4.368),ALBI≥-1.76(HR=2.452,95％CI:1.233-4.875),and central nervous system involvement(HR=4.674,95％CI:2.486-8.789)were independent risk factors affecting prognosis,while blood purification(HR=0.306,95％CI:0.153-0.612)was an independent protective factor for prognosis.The application of restricted cubic splines shows that the risk of death increases with the increase of ALBI score.The area under the ROC curve(AUC)of the ALBI score for predicting the risk of 1-week,2-week,4-week,and overall mortality were 0.825,0.807,0.700,and 0.693,respectively,indicating good predictive performance for early mortality risk.According to subgroup analysis results of clinical manifestations,compared with the ALBI＜-1.76 group,ALBI≥-1.76 was associated with age ≤2 years,EBV infection,HLH-1994/2004 treatment,concomitant respiratory failure,and ANC≤1.0 × 109/L,HB＜90 g/L,PLT＜100 × 109/L,TG≥3.0 mmol/L,LDH ≥ 1 000 U/L,APTT≥40 s,and FIB＜1.5 g/L(P＜0.05).Conclusion:The ALBI score is related to the clinical characteristics and laboratory indicators of sHLH,and can be used as a beneficial indicator for assessing the prognostic risk of sHLH in children.It has good accuracy and clinical application value in predicting the prognosis of sHLH in children.

Objective:To evaluate the safety and efficacy of ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique for the treatment of complex encapsulated lesions.Methods:A total of 48 patients(48 lesions) with complex encapsulated lesions who underwent ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique at Xi′an Chest Hospital from January to October 2023 were retrospectively enrolled, including 39 cases of encapsulated abscess, 7 cases of encapsulated effusion, and 2 cases of encapsulated haematoma; the distribution of the bacterial flora of the abscesses were as follows: 24 cases of tuberculous abscess, 14 cases of bacterial abscess, 1 case of bacterial combined bacterial-fungal abscess, and 7 cases of encapsulated effusion were tuberculous pleurisy, and the clinical data were analysed retrospectively. The maximum upper and lower diameters, right and left diameters, and anterior and posterior diameters of the lesions were measured by ultrasound before and after the operation. The patients′ various biochemical indicators (C-reactive protein, white blood cell count, neutrophil count, erythrocyte sedimentation rate) were detected. The intraoperative and postoperative complications, postoperative outcomes, and postoperative clinical symptoms were recorded.Results:Of the 48 patients, 39 were cured and discharged after negative pressure suction and rotatory excision technique, and 9 patients were cured and discharged after surgical incision and drainage of the lesions. The overall effective rate of negative pressure suction and rotatory excision treatment reached 81.25%, and the average number of days of tube placement was (11.81±7.22) days, and the average number of days of follow-up was (35.77±19.39) days. Compared with preoperative values, the upper and lower diameters, the left and right diameters, and the anterior and posterior diameters of the lesions were all reduced after operation [5.80 (4.95, 7.95)cm vs 8.00 (6.00, 11.82)cm, 4.00 (3.25, 5.00)cm vs 5.85 (4.52, 7.65)cm, 1.80 (1.00, 2.90)cm vs 3.40 (2.50, 6.15)cm, all P<0.01]; and postoperative C-reactive protein, white blood cell count and neutrophil count all decreased (all P<0.05). Before operation there were 31 cases of local swelling, 16 cases of pain, 12 cases of activity limitation, 12 cases of fever, 7 cases of chest tightness, and 6 cases of shortness of breath, and during postoperative follow-up, there were 4 cases of local swelling, 5 cases of pain, and 4 cases of activity limitation. The symptoms of fever, chest tightness, and shortness of breath all disappeared, and there was a statistically significant difference between preoperation and postoperation (all P<0.05). There were no adverse events or complications associated with the intraoperative and postoperative follow-up of negative pressure suction and rotatory excision treatment. Conclusions:Ultrasound-guided percutaneous negative pressure suction and invasive rotatory excision technique for the treatment of complex encapsulated lesions can significantly reduce lesion size, reduce inflammatory response and improve patient symptoms, which is a safe, effective and minimally invasive technique.