Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation in vivo and strong targeting. The application of liposome nano drug delivery system can improve the pharmacokinetic behavior and efficacy of some drugs in vivo to a certain extent, and reduce toxic and side effects. After liposome nanomedicine enter into the body, free drugs will be released, so there will be loaded drugs and free drugs in the body. Loaded drugs are drug repositories, free drugs are related to their efficacy and adverse reactions. Therefore, the pharmacokinetics study of liposomes should focus on both loaded drugs and free drugs. Quantitative analysis of free drugs, liposome particles and their materials is a big challenge. The bioanalysis and pharmacokinetics of liposome nanomedicines will be introduced and discussed in this review. We hope this review will provide a reference for the development of liposome nanomedicine.

Polymer nanomaterials have been attracted more and more attention because of their advantages such as long circulation, reduced immunogenicity and less side effects, and have become a hot research topic in nanomaterials. However, the number of polymer nanomedicines successfully applied in clinical application is very limited, and the unsatisfactory pharmacokinetic behavior is one of the main reasons for thisresult. After polymer nanoparticles enter the body, they will release free drugs and polymer excipients. Polymer nanoparticles are the loaded drugs and free drugs are the active chemicals for efficacy, while polymer excipients may cause excipient drug interactions. Therefore, the focus of the pharmacokinetics study of polymer nanoparticles should not be only limited to the free drugs themselves, but should also focus on the loaded drugs, free drugs and polymer excipients. The dynamic changes of polymer excipients and their metabolites pose new requirements and challenges for the bioanalysis of polymer nanomedicines. The characteristics and application scope of common analytical methods for detection polymer nanomedicines including chromatographic assay will be discussed in this paper. Moreover, this review will also summarize the absorption, distribution, metabolism and excretion of polymer nanomedicines. We hope this review will provide reference for the pharmacokinetics study, safety and effectiveness evaluation of polymer nanomedicines.

AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.

OBJECTIVE: To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors. METHODS: A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging. RESULTS: (1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm². The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival. CONCLUSION The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.
Humans ; Male ; Female ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Proto-Oncogene Proteins B-raf ; Prognosis ; Melanoma/surgery*

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens