Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective:To summarized the clinical characteristics and surgical management of anterior cervical enterogenic in pediatric patients. Methods:Clinical data were retrospectively analyzed for 9 children with pathologically confirmed anterior cervical enterogenic cysts（including bronchogenic and esophagogenic subtypes） treated at the Children's Hospital of Shandong University（Jinan Children's Hospital） between January 1, 2020, and November 30, 2023. Results:Nine patients（6 males and 3 females） were involved in this study, aged 14 days to 10 years old. There were 4 cases on the left side, 4 on the right side, and 1 in the middle of the neck. All patients presented with neck masses. The patients were followed up from 3 months to 35 months after surgery and recovered well, with no recurrence or complications observed. Conclusion:①Anterior intestinal cysts in children are rare and easy to be misdiagnosed. ②Concurrent branchial cleft fistulas or associated anomalies may coexist, necessitating comprehensive evaluation. ③Preoperative diagnosis is not easy and mainly depends on pathological diagnosis. ④The treatment of anterior cervical enterogenic cysts in children is surgical resection of the lesion.
Humans ; Male ; Female ; Child ; Retrospective Studies ; Child, Preschool ; Infant ; Neck ; Cysts/surgery*

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

The research focus of diabetes, a common chronic metabolic disease, has shifted from individual factors to environmental factors at the population level. Epidemiological studies suggest an association between exposure to environmental pollutants and the risk of diabetes. Major environmental pollutants include organochlorine pesticides, polychlorinated biphenyls, phthalates and their metabolites, and arsenics, which primarily enter the human body through the skin, respiratory tract, and digestive system. Long-term exposure to these pollutants can affect the pathology of diabetes through various mechanisms, such as promoting insulin resistance, causing insulin secretion deficiencies, inducing oxidative stress-induced glucose metabolism disorders, and affecting DNA methylation. However, the potential damaging mechanism of the impact of environmental pollutants on diabetes remain unclear. Limitations such as insufficient sample sizes, uncertainties regarding exposure time and dosage, and differences between single and co-exposures. In the future, it is necessary to focus on exploring and analyzing the mechanisms of environmental pollutant exposure on diabetes to develop effective prevention strategies, control and reduce the incidence and development of diabetes, and provide new insights into its diagnosis and treatment.

Objective To construct a list of quality scoring criteria for the attached sheet to the summary page of inpatient cases to achieve quantitative evaluation of the data quality.Methods It uses the Data Quality Management model of the American AHIMA as the evaluation framework to develop the list of data quality scoring criteria for the attached sheet,and score in Attached Sheet to the Summary Page of Inpatient Cases issued by the Hubei Provincial Health Commission as a demonstration.Results The average score of the 40 items in Attached Sheet to the Summary Page of Inpatient Casesis 6.725 out of 10.The main quality defects include that all items fail to clarify the person responsible for filling or the time limit for filling.In addition,some items are duplicated with the summary page(35%)or do not have a summary nature(40%).Conclusion Significant room exists for the improvement in the data quality of the attached sheet,especially in defining the person responsible and the time limit for filling in when setting up the items,making sure that the items supplement and extend the summary page,and applying effective quality control methods to the items.

Objective To investigate the feasibility of retroperitoneoscopy in the treatment of adrenal masses in infants under 6 months old.Methods From January 2020 to November 2023,retroperitoneoscopic surgery was performed in 5 infants under 6 months old with adrenal tumors.Their age was from 1 month and 18 days to 4 months and 27 days,and their body weight was 5-8 kg.The lesion was found by prenatal ultrasonography in 1 case and by abdominal ultrasonography for other reasons after birth in 4 cases.Ultrasound and CT indicated a diameter of 1.7-5.5 cm for the adrenal masses.Results The operations of adrenalectomy and tumor resection were completed under retroperitoneoscopy.The operative time was 65-135 min(median,94 min).The intraoperative blood loss was less than 10 ml.The postoperative drainage tube retention time was 3-6 d(median,5 d).Pathological diagnosis showed 4 cases of adrenal neuroblastoma and 1 case of adrenal hyperplasia.Follow-ups for 1-36 months(median,3 months)with abdominal ultrasound and CT scanning showed no recurrence or metastasis.Conclusion Retroperitoneoscopy is relatively safe for the treatment of adrenal tumors in infants under 6 months old(tumors with acceptable boundaries).

Objective To summarize the clinical experience of thoracoscopic treatment of anterior mediastinal enterogenous cysts.Methods From July 2019 to July 2023,27 children diagnosed as having anterior mediastinal enterogenous cysts were treated with total thoracoscopic surgery through the lateral thoracic approach(three port method)in our department.The patients were placed in a healthy lateral position.The observation hole was located in the 5th intercostal space under the scapula,and the other 2 operating holes were established based on the location of the lesion and the endoscopic diamond-shaped method,both of which were 5 mm trocars.The CO2 pneumothorax was established at a pressure of 6 mm Hg.The visceral pleura of the cyst was opened with an electric hook,the cyst was fixed and pulled by intestinal forceps,and the cyst was completely removed by forceps and electric hook separation alternately.Results No conversion to thoracotomy was required.Complete resection was performed in 26 cases,and residual cyst wall existed in 1 case.Esophageal muscular layer was opened in 9 cases.During the operation,cysts obstructed the surgical field of view in 5 cases,which was not conducive to observation.The cyst puncture and fluid extraction were performed.The operation time was 45-120 min(median,70 min).The amount of blood loss was 3-10 ml(median,5 ml).Postoperative hospitalization lasted for 2-5 d(median,3d).The 27 cases were followed up for 1-43 months(median,22 months),and there was no recurrence.The compressed trachea in 2 cases was all recovered,with emphysema fully recovered.Conclusions Thoracoscopic treatment of anterior mediastinal enterogenous cysts in children is safe and feasible.When the surrounding structure of the lesion is complex,it can be combined with bronchoscopic or gastroscopic surgery if necessary.

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 establish an evaluation system of pathogen detection rate of hospitalized patients before antimicrobial treatment based on process and outcome indicators,and study its application effect.Methods Hospi-talized patients with therapeutic antimicrobial treatment in a tertiary first-class hospital from July 2022 to June 2023 were selected as the study objects.Difference in process and outcome indicators were compared between before(Ju-ly-December 2022,control group)and after(January-June 2023,intervention group)the implementation of inter-vention in the evaluation system for pathogen detection rate of hospitalized patients before antimicrobial treatment.Results 41 577 and 27 052 hospitalized patients received therapeutic antimicrobial agents were included in the inter-vention group and control group,respectively.Pathogen detection rate and the accurate pathogen detection rate in the intervention group were both higher than those in the control group(74.2％vs 62.8％and 90.3％vs 82.5％,respectively),both with statistically significant differences(both P＜0.001).The goal achievement rate and im-provement rate for pathogen detection rate were 237.5％and 18.2％respectively,the goal achievement rate and im-provement rate for accurate pathogen detection rate were 104.0％and 9.5％respectively.For the process indica-tors,the conformity rate of detection and diagnosis,accurate collection rate,timely transfer rate,acceptance rate of pathogen specimens in the intervention group were all higher than those in the control group,differences were all statistically significant(all P＜0.001).For the outcome indicators,detection rates of targeted indicators and blood culture specimens,pathogen detection rate before treatment of restricted and special grade antimicrobial agent,as well as detection rate of sterile body fluid specimens in the intervention group were all higher than those in the con-trol group,with statistical significance(all P＜0.05).In addition,the positive rate of blood culture specimens in-creased from 18.5％before intervention to 21.7％after intervention,with statistically significant difference(P＜0.05).Conclusion The establishment of indicator evaluation system can improve the detection rate and accurate detection rate of pathogens before antimicrobial treatment,as well as the management quality and connotation of indicators.