Objective To investigate the value of secreted frizzled-related protein 1(SFRP1),GATA binding protein 3(GATA3)combined with human papillomavirus deoxyribonucleic acid(HPV-DNA)in predicting the risk of postoperative recurrence of high-grade cervical intraepithelial neoplasia(CIN)with positive thin-prep cytologic test(TCT).Methods A total of 200 patients with high-grade CIN and positive TCT results from July 2021 to July 2023 were selected as study subjects.All patients underwent cervical conization,and were divided into recurrence group and non-recurrence group according to the recurrence status one year after surgery.The clinical data,HPV-DNA viral load,and the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cer-vical tissues were compared between the two groups.The HPV-DNA viral load,SFRP1 mRNA,and GATA3 mRNA expression levels in patients with different CIN grades were compared,and their cor-relations with CIN grade and the risk of postoperative recurrence were analyzed.The predictive val-ues of SFRP1,GATA3,and HPV-DNA for the risk of postoperative recurrence were analyzed.Results Among 200 patients,2 were lost during the follow-up period.The recurrence group(n=30)had higher proportions of CIN grade Ⅲ,glandular involvement,positive surgical margins,high-risk human papillomavirus(HPV),higher HPV-DNA viral load,and a higher proportion of HPV positivity at 6 months after surgery compared with the non-recurrence group(n=168),and the differences were statistically significant(P＜0.05).The relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues of the recurrence group were lower than those of the non-recur-rence group,and the differences were statistically significant(P＜0.001).The HPV-DNA level in pa-tients with CIN grade Ⅲ was higher than that in those with CIN grade Ⅱ,and the relative expres-sion levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were lower than those in patients with CIN grade Ⅱ,and the differences were all statistically significant(P＜0.001).Spearman cor-relation analysis showed that HPV-DNA was positively correlated with CIN grade(P＜0.001),while the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were neg-atively correlated with CIN grade(P＜0.001).Logistic regression analysis showed that HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were independ-ent influencing factors for the risk of postoperative recurrence(P＜0.001).The receiver operating characteristic(ROC)curve results showed that the areas under the curve(AUCs)for predicting the risk of postoperative recurrence by HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were 0.787,0.781,and 0.764,respectively,with sensitivities of 80.00％,76.67％,and 76.67％,and specificities of 74.40％,73.81％,and 67.26％,respec-tively.The AUC for the combined prediction of the risk of postoperative recurrence by the three indica-tors was 0.924,with a sensitivity of 80.00％and a specificity of 93.45％,which was superior to the pre-dictive values of each indicator alone(Z=3.159,3.306,4.018,P＜0.001).Conclusion HPV-DNA,SFRP1,and GATA3 in cervical tissues have certain predictive values for the risk of postoperative re-currence in patients with high-grade CIN and positive TCT results,and combined detection can im-prove the predictive efficacy.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder involving digestive, renal, respiratory, and nervous systems caused by SLC7A7 gene mutation.It was first reported in Finland and now has been found worldwide.A total of 8 cases have been reported in China.The abnormal function of the y + amino acid transporter caused by SLC7A7 gene mutation can explain some clinical features, but the pathophysiological mechanism underlying the associated lung, kidney and blood system disorders is not clear.The varying clinical manifestations of LPI often lead to misdiagnosis or delayed diagnosis.This article reviews the pathogenesis, clinical characteristics, diagnosis and treatment of LPI, to enhance clinicians′ understanding of this disease.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

Objective:To investigate the clinical features of pertussis in children and analyze the risk factors of severe pertussis.Methods:The clinical data of 248 children with pertussis hospitalized in Hunan Children′s Hospital from March 2018 to March 2022 were analyzed retrospectively.According to the age at admission, the patients were divided into two groups: ≤3 months and > 3 months.According to the patient′s condition, they were classified into ordinary group and severe group.According to the pathogens detected, the children were divided into single infection group and mixed infection group.The independent sample t-test, chi- square test were used to analyze the clinical indexes of the infants in above groups. Results:(1)Of 248 hospitalized children with pertussis, 204 cases (82.2%) were less than 1 year old, 92 cases (37.0%) had contact with a coughing family member before, and 169 cases (68.1%) were unvaccinated.Among 248 children, 193 cases (77.8%) had an elevated white blood cell count, and 145 cases (58.4%) had mixed infections.The most common pathogen was respiratory syncytial virus [29/248(11.6%)]. About 173 cases (69.7%) had concurrent pneumonia, and 35 cases (14.1%) had pulmonary consolidation.(2)Compared with the group > 3 months of age, more patients in the group ≤3 months of age had contact with a coughing family member before, and suffered from cyanosis, dyspnea, respiratory failure, heart failure and pertussis encephalopathy ( χ2=4.612, 20.810, 7.882, 16.617, 13.740, 7.846, all P<0.05). The proportions of patients in the group ≤3 months of age required intensive care unit(ICU) hospitalization and mechanical ventilation were higher than those in the group > 3 months of age ( χ2=14.810, 21.436, all P<0.05). The mortality of the group ≤3 months of age was higher than that of the group >3 months of age ( χ2=12.016, P<0.05). Children ≤3 months of age had a higher WBC level [(27.83±27.70)×10 9/L vs.(23.34±15.28)×10 9/L, t=22.244, P<0.001], longer duration of spasmodic cough [(16.56±9.33) d vs.(15.06±6.16) d, t=10.145, P=0.002] and longer hospitalization time [(11.47±10.48) d vs.(9.48±4.80) d, t=20.050, P<0.001] than those >3 months of age.(3)Compared with the ordinary group, a higher proportion of children in the severe pertussis group were under 3 months old, and had not been vaccinated against pertussis vaccine ( χ2=14.803, 4.475, all P<0.05). The ratio of patients with dyspnea, an lymphocyte count/neutral cell(LC/NC) ratio <1, mixed infections, lung consolidation and pleural effusion in the severe pertussis group was higher than that in the ordinary group ( χ2=116.940, 43.625, 13.253, 106.370, 11.874, all P<0.05). The patients in the severe pertussis group had a higher WBC [(61.66±29.63)×10 9/L vs.(18.83±10.00)×10 9/L, t=112.580, P<0.001] and a lower LC (0.494±0.186 vs.0.676±0.132, t=13.752, P<0.001) than those in the ordinary group.(4)Compared with the single infection group, the proportions of children with fever, dyspnea, fine moist lung rales, an LC/NC ratio <1, and lung consolidation were higher in the mixed infection group ( χ2=8.909, 6.804, 7.563, 8.420, 12.458, all P<0.05). More children in the mixed infection group required ICU hospitalization and mechanical ventilation than those in the single infection group ( χ2=11.677, 7.397, all P<0.05). The mixed infection group had higher respiratory failure and death rates than the single infection group ( χ2=7.980, 4.267, all P<0.05). Compared with the single infection group, the mixed infection group had a higher WBC level [(27.73±24.13)×10 9/L vs.(21.25±14.65)×10 9/L, t=13.318, P<0.001], longer hospitalization time [(11.593±9.010) d vs.(8.339±4.047) d, t=17.283, P<0.001], and a smaller LC ratio (0.626±0.165 vs.0.684±0.132, t=7.997, P=0.005). (5) Logistic regression analysis showed that age ≤3 months, peak WBC and dyspnea were risk factors of severe pertussis. Conclusions:Hospitalized pertussis children are prone to pneumonia and pulmonary consolidation.Patients aged ≤3 months with a large WBC and dyspnea easily develop into severe pertussis.Monitoring blood routine is helpful for judging the severity of the disease.Mixed infections increase the incidence of complications and can impair the treatment effect.

The increasing incidence of allergic diseases in children has become a global public health problem, which not only endangers physical health, but also imposes a heavy economic burden on society and families.Allergen immunotherapy is a cause-specific treatment therapy for allergic diseases in children, which can change the natural course of allergic diseases and works by inducing the body to establish immune tolerance to allergens.Allergen immunotherapy can not only reduce the clinical symptoms and medication use of children, but also prevent allergic reactions to new allergens, and has good efficacy and safety.This paper reviews the research progress of allergen immunotherapy in children with allergic diseases, especially respiratory allergic diseases, in order to provide more treatment options and new ideas for clinical practice.

Objective:To investigate the clinical characteristics and prognosis factors in children with pneumocystis carinii pneumonia (PCP) without human immunodeficiency virus (HIV) infected.Methods:From January 2017 to December 2020, 35 non-HIV infected patients with PCP were admitted to Hunan Children′s Hospital.According to the prognosis at discharge, they were divided into survival group and death group.The clinical characteristics of two groups were compared, and the prognostic factors were analyzed.Results:The age of 35 patients ranged from 1 month to 15 years, including 24 males and 11 females.Seven patients(20.0%) had primary immunodeficiency, 5 patients(14.2%) had autoimmune disease, and 4 patients(11.4%) had renal disease.Eighteen patients were treated with long-term hormone and 13 patients were treated with immunosuppressive agents before the onset of the disease.Clinical symptoms included shortness of breath or dyspnea, cough, fever and so on, while with few pulmonary signs.Peripheral blood lymphocyte count was less than 1.5×10 9/L in 18 cases.The median LDH was(654.94±57.66)U/L; Fungal D-glucan increased in 13 cases.The median P/F was(121.29±23.25)mmHg, and P/F was less than 200 mmHg in 16 cases.CD4 cells were less than 500/μL in 15 cases and less than 200/μL in 8 cases.The imaging findings were mainly consolidation or patellar shadow, diffuse ground glass shadow, 3 cases with pleural effusion, and 1 case with pneumothorax.Twenty-two cases survived and 13 died, with a mortality rate of 37.1%.There were statistically significant differences in hospitalization days, CD4 cell count, Fungal D-glucan, P/F, ICU admission and invasive mechanical ventilation between two groups( P<0.05). Logistic multivariate analysis showed that decreased P/F value was an independent risk factor affecting the prognosis of non-HIV infected children with PCP ( OR=0.006, 95% CI 0.975-1.000). Conclusion:The clinical manifestations, laboratory examinations and imaging examinations of non-HIV infected patients with PCP lack specificity.When a diagnosis is suspected, high-resolution CT should be performed based on the results of peripheral blood lymphocyte count, CD4 cell count, fungal D, LDH, and blood gas analysis results as soon as possible, compound sulfamethoxazole should be used timely.Decreased P/F value is an independent factor affecting the prognosis of non-HIV children with PCP.

The clinical manifestation, laboratory findings, and imaging examination of a baby with familial glucocorticoid deficiency were summarized. The patient presented achypnea, cyanosis, and pigmentation of the whole body skin, no convulsion and hypoglycemia found. Laboratory findings revealed low blood cortisol and high blood ACTH levels. A 1-bp homozygous deletion(c.106+ 1delG) in intron 3 of melanocortin 2 receptor accessory protein(MRAP) gene in the patient was found. His parents were found to be heterozygous carrier for the same mutation, without any clinical manifestation.

Objective:To explore the clinical and genetic characteristics of a Chinese baby with perinatal hypophosphatasia (HPP) and his parents for better understanding of the disease.Methods:The clinical data of the patient with HPP was carefully collected. The laboratory and radiographic examination data were taken for this baby patient. Sequencing for all the twelve tissue-nonspecific alkaline phosphatase(ALPL) exons and the flanking exon-intron junctions were performed in the proband and his parents with their genomic DNA from peripheral blood.Results:The blood level of alkaline phosphatase was decreased in this patient while serum calcium level was increased. His bone revealed chondrodysplasia-like change. Compound heterozygous mutations were found in the proband, with c. 346G>A(p.A116T) in exon 5 and c. 1171C>T(p.R391C) in exon 10. His father and mother were without clinical manifestation while respectively carried c. 346G>A(p.A116T and c. 1171C>T(p.R391C) missense mutations, suggesting an autosomal recessive inheritance in this family.Conclusion:Perinatal HPP has a high mortality rate. Skeletal deformities, hypercalcemia, and low level of ALP are important in the differential diagnosis of perinatal HPP.

OBJECTIVE: To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant. CONCLUSION The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.
Adult ; Diabetes Insipidus, Nephrogenic/genetics* ; Exons ; Female ; Frameshift Mutation ; Humans ; Hydrochlorothiazide/therapeutic use* ; Infant, Newborn ; Male ; Pedigree ; Receptors, Vasopressin/genetics*