Objective:To compare the clinical features of severe Mycoplasma pneumoniae pneumonia (SMPP) in pediatric intensive care units (PICU) before and after the COVID-19 pandemic.Methods:A retrospective study was conducted in the PICU of Shanghai Children's Hospital. Clinical and laboratory data were collected from medical records of SMPP patients admitted to the PICU before (January to December 2019) and after (March 2023 to February 2024) the COVID-19 pandemic. Patients admitted in 2019 were categorized as the pre-COVID-19 group, while those admitted in 2023-2024 were classified as the post-COVID-19 group.Results:A total of 287 children with SMPP were included, comprising 155 males and 132 females. The pre-pandemic group consisted of 180 cases, while the post-pandemic group had 107 cases. Macrolide-resistant Mycoplasma pneumoniae (MRMP) was detected in 270 cases (94.1%), with no significant difference in MRMP prevalence between the two groups [101 cases (94.4%) vs. 169 cases (93.9%), Z= 0.031, P = 0.861]. The median age of the post-pandemic group was higher than that of the pre-pandemic group [72 (42, 108) months vs. 42 (24, 68) months, Z= 6.438, P < 0.001].Comparisons of complications between the post-pandemic and pre-pandemic groups were as follows: pleural effusion [20 cases (18.7%) vs. 81 cases (45.0%), χ2=20.365, P< 0.001], shock [4 cases (3.7%) vs. 79 cases (43.9%), χ2=52.628, P< 0.001], gastrointestinal dysfunction [2 cases (1.9%) vs. 24 cases (13.3%), χ 2=9.359, P=0.002], liver dysfunction [9 cases (8.4%) vs. 46 cases (25.6%), χ2=12.733, P< 0.001], and renal injury [0 cases vs. 10 cases (5.6%), P=0.015].There was no significant difference in the incidence of respiratory failure [102 cases (95.3%) vs. 172 cases (95.6%), χ2=0.008, P=0.928]. However, the number of cases requiring high-flow oxygen therapy and mechanical ventilation was significantly lower in the post-pandemic group compared to the pre-pandemic group [14 cases (13.3%) vs. 48 cases (26.7%), 21 cases (20.3%) vs. 122 cases (67.8%), all P<0.05].The time from symptom onset to the initiation of tetracycline/quinolone therapy was shorter in the post-pandemic group compared to the pre-pandemic group [7 (3, 10) days vs. 9 (6.3, 11) days, χ2=-3.565, P< 0.001]. The proportion of patients who had already received tetracycline/quinolone therapy before admission to the PICU was significantly higher in the post-pandemic group compared to the pre-pandemic group [25 cases (23.4%) vs. 2 cases (1.1%), χ 2=10.009, P=0.002].Both the total hospital stay and PICU stay were shorter in the post-pandemic group compared to the pre-pandemic group [10.0 (8.0, 14.0) days vs. 15.5 (12.0, 22.0) days, 5 (3.0, 8.0) days vs. 7.0 (5.0, 10.0) days, all P=0.000]. All 7 deaths occurred in the pre-pandemic group, including 5 cases with co-infections and 2 cases with underlying diseases. Conclusions:In the post-COVID-19 era, SMPP cases in the PICU were predominantly observed in children over 5 years old, with a lower incidence of shock, gastrointestinal disorders, liver injury, and kidney injury compared to the pre-pandemic period. Patients with macrolide-resistant Mycoplasma pneumoniae who received timely treatment with tetracycline/quinolones exhibited favorable outcomes.

Neurofibromatosis type 1（NF1）is one of the most common autosomal dominant disorders. The disease is caused by mutations in the NF1 gene，which can involve multiple systems and have a variety of clinical manifestations，including café au lait macules，lisch nodules，neuroglioma，autism spectrum disorder，learning difficulties，neurofibromas，and skeletal dysplasia，et al.In previous studies on the pathogenesis of NF1，most of them have focused on the regulation of the RAS signaling pathway by neurofibromin. In recent years，researchers start exploring pathways other than RAS signaling to explore the potential functions of neurofibromin. This article reviews the research progress on the pathogenesis of NF1 in recent years，aiming to provide new ideas for treatment.

Hypoxic pulmonary hypertension(HPH)is a kind of chronic high-altitude sickness disease,which is also the initiation link of high-altitude sickness such as pneumocardial disease and high-altitude pulmonary edema.Its main features are persistent vasoconstriction and irreversible remodeling of blood vessels.HPH has greatly impacted the health of people in the plat-eau section.As a typical representative of ethnic medicine,Zang medicine embodies the wisdom of the Zang people in their long-term struggle against diseases.Adapting to local conditions for a long time,Zang medicine has unique advantages in the treatment of HPH.By reviewing the pathogenesis of HPH and the research of single Zang medicine and the complex prescription of Zang medicine in the treatment of HPH,this article aims to provide a theoretical basis for the physiological and pathological research of HPH and to provide a reference for the clinical application of Zang medicine.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective:To investigate the etiological distribution of hydronephrosis caused by upper uri-nary tract obstruction in adult patients and to improve the diagnostic accuracy for this condition.Me-thods:The clinical information of adult patients with newly diagnosed hydronephrosis in Upper Urinary Tract Repair Outpatient Clinic of Peking University First Hospital from May 2020 to May 2021 were pro-spectively and continuously collected.Patients with ureteral calculi or upper urinary tract tumor were ex-cluded.A total of 767 patients were involved.The underlying causes of upper urinary tract obstruction were identified by senior urological surgeons according to symptoms,medical history,physical examina-tion,and a range of diagnostic imaging techniques including ultrasound,computed tomography(CT),magnetic resonance imaging(MRI),retrograde pyelography,antegrade pyelography,radionuclide reno-gram and ureteroscopy.Results:Among the 767 patients,359(46.8％)were male and 408(53.2％)were female.The median age of these patients was 37 years(range,14-84 years).Hydronephrosis was observed at left-sided in 357 cases(46.6％),right-sided in 251 cases(32.7％),and bilateral in 159 cases(20.7％).The causes of hydronephrosis were classified as follows:(1)Non-iatrogenic factors were found in 464 cases(60.5％).These included urinary malformations in 355 cases(76.5％),infec-tion in 29 cases(6.3％),pelvic lipomatosis and/or cystitis glandularis in 23 cases(5.0％),ureteral en-dometriosis in 18 cases(3.9％),retroperitoneal fibrosis in 15 cases(3.2％),trauma in 7 cases(1.5％)and other non-iatrogenic factors in 12 cases(2.6％).Some of these patients had multiple non-iatrogenic causes.Among the 355 cases with urinary system malformations,252 cases(71.0％)had ureteropelvic junction obstruction.(2)Iatrogenic ureteral injuries accounted for 210 cases(27.4％),including 112 cases(53.3％)of urological surgical injuries,51 cases(24.3％)of radiotherapy for malignant tumor re-lated injuries,34 cases(16.2％)of gynecological and obstetrical surgical injuries,and 13 cases(6.2％)of general surgical injuries.(3)The cause of hydronephrosis remained unknown in 93 cases(12.1％).Conclusion:Hydronephrosis in adults due to upper urinary tract obstruction has a diverse range of cau-ses,with urinary malformations and iatrogenic ureteral injuries being significant contributors.Urological surgeon involved in upper urinary tract reconstruction should be familiar with these potential causes to fa-cilitate accurate diagnosis and effective treatment.

microRNA(miRNA)is a 22nt long sin-gle-stranded non-coding RNA that is involved in a variety of physiological and pathological processes.Bronchial asthma is a heterogeneous disease,and airway inflammation is one of the important mecha-nisms of its pathogenesis.Asthma can be classified into different types based on the different immune mechanisms involved in its pathogenesis,and the mechanism of airway inflammation also varies be-tween different types of asthma.This article reviews the research progress of miRNA in asthma airway inflammation and endotype,and explores the pathogenesis and treatment prospects of miRNA in asthma airway inflammation and endotype.

Objective:To explore the performance and value of urine DNA methylation technology in non-invasive diagnosis of upper tract urothelial carcinoma (UTUC).Methods:A retrospective analysis was conducted on the of 107 patients with UTUC (UTUC group) and 121 patients with benign upper urinary tract diseases (control group) admitted to Sun Yat sen Memorial Hospital and Peking University First Hospital from August 2019 to March 2021. There were 64 males (59.8%) and 43 females (40.2%) in the UTUC group, with the age of (67 ± 10) years old.There were 50 cases (46.7%) of ureteral cancer, 42 cases (39.3%) of renal pelvis cancer, and 15 cases (14.0%) of renal pelvis cancer combined with ureteral cancer.45 cases (42.0%) of non muscular infiltrative UTUC, 51 cases (47.7%) of muscular infiltrative UTUC, and 11 cases (10.3%) of unclear stage.There were 14 cases (13.1%) with low tumor grade and 93 cases (86.9%) with high grade. There were 81 males (66.9%) and 40 females (33.1%) in the control group, with the age of (52 ± 14) years old.There were 104 cases (86.0%) of urinary stones, 13 cases (10.7%) of ureteral stenosis or polyps, and 4 cases (3.3%) of simple hydronephrosis. Sixty cases (56.1%) in the UTUC group and 11 cases (9.1%) in the control group underwent urine cytology examination. Seventy-two cases (67.3%) in the UTUC group and 9 cases (7.4%) in the control group underwent urine in situ fluorescence hybridization (FISH) examination. Quantitative PCR detection based on ONECUT2 and VIM gene methylation was performed on urine sediment samples from both groups. If ≥ 1 gene was positive, it was determined as positive, and if both genes were negative, it was determined as negative. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of urine cytology, FISH, and urine DNA methylation tests were evaluated based on pathological or clinical diagnosis criteria.Results:The overall sensitivity of urine DNA methylation test was 84.1%, specificity was 90.9%, accuracy was 87.7%, positive predictive value was 89.1%, and negative predictive value was 86.6%, respectively. It's sensitivity and accuracy were significantly higher than that of urine cytology (43.3%, P<0.05)(52.1%, P<0.05)and FISH (69.4%, P<0.05)(71.6%, P<0.05). The accuracy was significantly higher than that of urine cytology (52.1%, P<0.05) and FISH (71.6%, P<0.05); There was no statistically significant difference in specificity between urine cytology (100.0%) and FISH (88.9%) ( P>0.05). The results of subgroup analysis showed that the diagnostic sensitivity of urine DNA methylation test for tumors in different locations was 74.0% (37/50 cases) for ureteral cancer, 90.5% (38/42 cases) for renal pelvis cancer, and 100.0% (15/15 cases) for renal pelvis cancer combined with ureteral cancer.The diagnostic specificity for different benign diseases was 92.3% (96/104 cases) for urinary stones, 84.6% (11/13 cases) for ureteral stenosis and polyps, and 75.0% (3/4 cases) for simple hydronephrosis. The diagnostic sensitivity of urine DNA methylation test for low-grade UTUC was 64.3%, significantly higher than that of urine cytology (20.0%) and FISH(36.4%)( P<0.05). The diagnostic sensitivity for high-level UTUC was 87.1%, which was higher than that of urine cytology (48.0%) and FISH (75.4%)( P<0.05). The diagnostic sensitivity for non muscular invasive UTUC was 77.8%, which was significantly higher than that of urine cytology (29.2%) and FISH (64.5%)( P<0.05). The diagnostic sensitivity for myometrial infiltrative UTUC was 88.2%, which was superior to urine cytology (53.6%) and FISH (72.7%)( P<0.05). The sensitivity and specificity of urine DNA methylation test in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were 83.0% and 92.0%, respectively.It’s sensitivity and specificity in Peking University First Hospital were 85.2% and 85.7%, respectively. Conclusions:The urine ONECUT2 and VIM gene methylation assay have high sensitivity and accuracy in upper urinary tract urothelial carcinoma, which are superior to urine cytology as well as FISH.

In the past decade, significant progress has been made in the study of epilepsy-causing genetic mutations and the molecular mechanisms of epilepsy clinical manifestations.A growing number of studies have shown that the mechanism of action of pathogenic genes related to clinical symptoms shows significant correlation.In the selection of antiepileptic drugs for patients with different gene mutation, early identification of pathogenic genes has guiding significance for the selection of antiepileptic drugs.This review summairzes common epilepsy pathogenic genes, including ion channels genes, cellular metabolism related genes and cell signaling pathway related genes, and research progress on therapeutic targets corresponding to pathogenic genes in recent years.As research deepens, specific gene defects and their machanisms of action provide a basis for studying new treatment methods.

IL1RAPL1 gene is one of the genes related to X-linked nonspecific mental retardation(MRX), but its pathogenic mechanism has not been fully clarified.Interleukin-1 receptor accessory protein like 1(IL1RAPL1) is a synaptic adhesion molecule located on postsynaptic membrane.The mutation of IL1RAPL1 gene can lead to the deletion or dysfunction of this protein.Recent studies have shown that the IL1RAPL1 protein regulates dendritic formation and mediates the activity of IL-1β molecules on dendritic morphology.This review describes the latest advances in synaptic and neuronal functions of IL1RAPL1, and summarizes some gene mutations that have been found to be associated with mental retardation(MR)and autism spectrum disorder(ASD), to provide evidence for clinical diagnosis and treatment.