OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Hypoparathyroidism-sensorineural deafness-renal dysplasia syndrome (HDR). METHODS: A female neonate with HDR syndrome and thyroid deficiency detected at the First Affiliated Hospital of Zhengzhou University on December 6,2023 was selected as the study subject, Low-coverage whole-genome sequencing (Lc WGS) and whole exome sequencing (WES) were carried out. Using "hypoparathyroidism""sensorineural deafness""renal dysplasia""HDR""Barakat" and"GATA3" as keywords, the CNKI, Wanfang Data Knowledge Service Platform and PubMed database were searched, and the retrieval time was set from the establishment to March 2025. RESULTS: A proband, a full-term female infant, had presented with feeding difficulty, micrognathia, and low-set ears. Serological test revealed hypocalcemia, hyperphosphatemia, hypoparathyroidism, low T3, low T4 and high TSH. Hearing test revealed bilateral sensorineural deafness. Ultrasonic test revealed absence of right kidney and thyroid. WES revealed that the she has harbored a deletion of approximately 6.67 Mb at 10p15.1p13, and Lc WGS confirmed the presence of a 6.70 Mb deletion in the same region, which was verified as a de novo variant. Literature review suggested that HDR was rarely diagnosed among neonates. Among the nine cases diagnosed in neonatal period, 66.6% (6/9) exhibited the typical triad, 77.7% (7/9) had hypoparathyroidism with hypocalcemic convulsion as the initial symptom, 22.2% (2/9) had sensorineural hearing loss or renal malformation, and 66.6% (6/9) had multiple malformations including facial dysmorphism and congenital heart disease. 55.5% (5/9) had a large deletion in the 10p15 region, whilst 33.3% (3/9) had a single gene variant. The range of the deletion had correlated with the diversity of clinical phenotypes in HDR syndrome, but the classic triad of symptoms may presented in any combination, independent of deletion size. Association of HDR with thyroid deficiency has been unreported previously. CONCLUSION For neonates presenting with one of the symptoms of HDR triad or in combination with other malformations, genetic testing should be carried out.
Humans ; Hypoparathyroidism/diagnosis* ; Female ; Infant, Newborn ; Hearing Loss, Sensorineural/diagnosis* ; GATA3 Transcription Factor/genetics* ; Nephrosis/genetics* ; Phenotype ; Exome Sequencing

OBJECTIVE To investigate and analyze the operational costs and current charging policies of pharmacy intravenous admixture service （PIVAS） in China， and provide a reference for promoting high-quality and sustainable development of PIVAS. METHODS Questionnaires were distributed in 30 provinces， autonomous regions， and municipalities across the country through the “Wenjuanxing” platform from May 6th to July 1st， 2022. The operational costs， charging status and suggestions of PIVAS were investigated and analyzed. RESULTS A total of 761 PIVAS participated in the survey nationwide， including 666 tertiary medical institutions， 93 secondary medical institutions， and 2 primary medical institutions. Approximately 60.58% of PIVAS had implemented a charging system that allowed charges. Among them， most PIVAS required inspection and evaluation before charging. The annual operating cost of PIVAS in China was approximately 2 098 100 yuan， with the integrated operating cost comprising 89.36% of the total， while the dispensing cost accounted for only 10.64%. Human costs emerged as the highest annual consumption （74.20%）， followed by decoration and facility maintenance costs （4.77%） and equipment acquisition costs （3.44%）. Regarding charges for different drugs nationwide， common drugs had an average charge standard of 4.39 yuan per bag while antibacterial drugs averaged 5.01 yuan per bag； hazardous drugs had an average charge of 23.17 yuan per bag， whereas parenteral nutrition solutions averaged 38.75 yuan per bag. However， the recommended average charges of the four drugs mentioned above were 6.71， 9.63， 38.35 and 44.03 yuan per bag， respectively. CONCLUSIONS At present， there is no unified inspection and evaluation standard and charging standard in China. Moreover， the current charging standard is lower than the recommended standard. It is necessary to combine operational costs and develop more reasonable and fair charging standards.

There are a large number of individuals with HBV infection in China, which seriously endangers public health safety. As a first-line drug used in clinical practice, tenofovir alafenamide fumarate (TAF) has the characteristics of strong efficacy, low drug resistance, and bone and kidney safety. This article summarizes the role of TAF in patients with special types of chronic hepatitis B, such as low-level viremia, multidrug resistance, pregnancy, liver failure, and liver transplantation, and the analysis shows that TAF can reduce viral load in patients with low-level viremia to achieve virologic response, provide new regimens for patients with drug resistance, block mother-to-child transmission, reduce the mortality rate of patients with end-stage liver disease, and improve renal function in patients with chronic kidney disease.

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Objective:To explore the correlation between Traditional Chinese Medicine (TCM) excessive patterns and clinical characteristics of acute exacerbation of chronic obstructive pulmonary disease (COPD) complicated with chronic pulmonary heart disease (CPHD) in high altitude environment.Methods:Patients with acute exacerbation of COPD complicated with CPHD admitted to the Pulmonology Department of Qinghai Provincial Hospital of Traditional Chinese Medicine from December 2016 to November 2017 were selected. Demographic data and clinical medical characteristics data of the patients were collected, and TCM patterns differentiation was conducted. The correlation between each pattern type and clinical characteristics and all collected laboratory indexes were analyzed by multivariate logistic regression.Results:Phlegm obstructing lung pattern showed a negative correlation relationship with mMRC score [ OR=0.419, 95% CI (0.219-0.802), P=0.009], PCT [ OR=8.132×10 -11, 95% CI (1.632×10 -16-4.1×10 -5), P<0.001], Hb [ OR=0.971, 95% CI (0.952-0.989), P=0.002] and PaCO 2[ OR=0.914, 95% CI (0.853-0.980), P=0.011]; turbid phlegm obstructing lung pattern showed a negative correlation relationship with gender(0 male, 1 female) [ OR=0.427, 95% CI (0.204-0.892), P=0.024], Hb [ OR=0.960, 95% CI (0.945-0.975), P<0.001], and there was a positive correlation relationship with LVEF [ OR=1.061, 95% CI (1.006-1.118), P=0.028]; phlegm-heat obstructing lung pattern showed a negative correlation relationship with Hb [ OR=0.950, 95% CI (0.927-0.974), P<0.001]and cardiac function grade [ OR=0.468, 95% CI (0.248,0.881), P=0.019], and there was a positive correlation relationship with PCT [ OR=1.118×10 8, 95% CI (1.466×10 4-8.523×10 11), P<0.001] and D-D [ OR=2.283, 95% CI (1.300-4.010), P=0.004]; there was a negative correlation between phlegm and stasis blocking lung pattern with cardiac function grade[ OR=0.309, 95% CI (0.167-0.570), P<0.001], and there was a positive correlation relationship with Hb[ OR=1.060, 95% CI (1.042-1.078), P<0.001]; there was a negative correlation between wet phlegm and blood stasis heat pattern with PCT [ OR=1.266×10 -13, 95% CI (1.658×10 -21-0.1×10 -4), P<0.001], SaO 2 [ OR=0.934, 95% CI (0.892-0.979), P=0.004], LVEF [ OR=0.896, 95% CI (0.826-0.971), P=0.008], D-D [ OR=0.030, 95% CI (0.002-0.508), P=0.015], and there was a positive correlation relationship with CRP [ OR=1.042, 95% CI (1.018-1.067), P<0.001], RBC [ OR=3.411, 95% CI (1.684-6.910), P<0.001], cardiac function grade [ OR=8.573, 95% CI (2.410-30.504), P<0.001], pulmonary arterial pressure difference [ OR=2.091, 95% CI (1.243-3.516), P=0.005]. Conclusions:Male patients are more prone to phlegm and turbidities than female patients. PCT and D-D were the main risk factors of phlegm-heat obstruction syndrome. Elevated hemoglobin is a risk factor for patients with phlegm stasis and lung syndrome. Heart function classification is the main risk factor of phlegm-dampness-stasis heat syndrome.

Objective:To investigate the effect of curcumin on the nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in cardiomyocytes of rats with early sepsis and its mechanism.Methods:Twenty-four male SD rats were randomly divided into three groups: the sham-operated group (sham group, n=8), the sepsis group ( n=8), and the curcumin intervention group (Cur group, n=8). A rat model of sepsis was prepared by cecal ligation and perforation (CLP). After modeling, 100 mg/kg of curcumin was intraperitoneally injected and repeated 24 h later. Rats in the sepsis group were injected with normal saline. The levels of myocardial injury-specific troponin T (cTnT) in rat plasma were detected by ELISA at 6, 24, and 48 h. Hematoxylin-eosin (HE) staining was used to observe the pathological injury of the myocardium in the myocardial tissue of rat at 48 h. The apoptosis of cardiomyocytes was detected by TUNEL assay. The expression levels of Cleaved caspase-1, NLRP3 and IL-1β protein were detected by Western blot, and the ultrastructural changes of the cardiomyocytes were observed under a transmission electron microscope. Results:The levels of cTnT in rat plasma at 6, 24, and 48 h in the Cur group were significantly lower than those in the sepsis group ( P<0.05). HE staining showed infiltration, cell edema and necrosis of myocardial inflammatory cells in the sepsis group, while only partial cell edema and necrosis were observed in the Cur group. TUNEL assay showed that the apoptosis of cardiomyocytes in the Cur group was significantly lower than that in the sepsis group [(28.4±2.3)% vs. (43.6±3.8)%, P<0.05]. The expression levels of Cleaved caspase-1, NLRP3 and IL-1β in the Cur group were lower than those in the sepsis group and higher than those in the sham-operated group ( P<0.05). Under transmission electron microscopy, the nuclei in the sham-operated group had intact membranes and uniform chromatin distribution; in the sepsis group chromatin margination, pyknosis, mitochondrial cristae breakage, cavitation, and partial breakage of sarcomere were observed; while in the Cur group partial chromatin margination, slightly edema and dilation of mitochondria, with basically complete morphology were observed. Conclusions:Curcumin inhibits NLRP3-mediated acute myocardial injury in septic rats, and its mechanism may be related to pyroptosis induced by the down-regulation of the expression of Cleaved caspase-1 and IL-1β protein.

Urinary tract infections (UTIs) are common, recurrent infections that can range from mild to life-threatening. High recurrence rates of UTIs and increasing antimicrobial resistance may place a greater financial burden on the patients with UTIs. Thus, UTIs is becoming an increasingly serious public health problem. This review summarized how pathogens adhered to and colonized host cells, the important role of bacterial pili in the development of UTIs and the pathogenic mechanisms of different pathogens in UTIs and catheter associated urinary tract infections (CAUTIs). Elucidating the molecular mechanisms of host-pathogen interactions and the pathophysiological consequences of these interactions in UTIs is conducive to further understand the pathogenesis of UTIs.

Objective:To evaluate the diagnostic effects of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rapid screening of rifampicin-resistant tuberculosis.Methods:The clinical data of 150 patients diagnosed with tuberculosis by Bactec MGIT 960 liquid culture drug susceptibility in Zhejiang Chinese Medicine and Western Medicine Integrated Hospital from September 2016 to August 2019 were collected, including Xpert MTB/RIF and gene chip results. The isolated and cultured strains from patients were subjected to fluorescence PCR melting curve detection. Using Bactec MGIT 960 drug susceptibility results as the reference, the diagnostic efficacy of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rifampicin resistance were analyzed, and the receiver operating characteristic curve (ROC) was drawn for comparative analysis.Results:Take Bactec MGIT 960 as the gold standard, the sensitivity of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rifampicin resistance were 88.89% (16/18), 94.44% (17/18), 88.89% (16/18) respectively; the specificity were 96.21% (127/132), 96.21% (127/132), 95.45% (126/132), respectively. There was no statistically significant difference in the sensitivity and specificity among the three detection methods ( P>0.05). The Kappa values of the three molecular methods for detecting rifampicin resistance were 0.794, 0.827 and 0.770, respectively. The three detection methods have good diagnostic value for rifampicin resistance ( P<0.01), but there is no statistically significant difference between the three methods ( P>0.05). There were 8 cases of inconsistent results between the three methods and Bactec MGIT 960 drug sensitivity. Conclusion:Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology have comparable ability to detect rifampicin resistance, all of these have high sensitivity and specificity for detecting rifampicin resistance and are suitable for rapid screening.

Objective To study the epidemiological characteristics of norovirus (NV) and rotavirus (RV) in children with diarrhea. Methods In this study, fecal specimens of 2 135 children with diarrhea admitted to our hospital from January 2019 to December 2019 were collected. The infection of NV and RV virus was detected by immunochromatography and ELISA, respectively. The epidemiological characteristics of RV virus. Results The total positive detection rate of 1 388 children was 65.01% (1 388/2 135), and the positive detection rate of RV virus was 34.52% (651/2 135), which was higher than 30.49% (737/2 135) of NV virus (χ²=7.895, P<0.05); there is no difference in the positive detection rate of NV virus among children of different genders (P>0.05), the positive detection rate of RV in males is 61.74%, higher than that of females 38.26% (χ²=25.318 , P<0.001); the age of children infected with NV and RV viruses are within 2 years old, and the cumulative positive detection rates are 64.21% (418/651) and 60.92% (449/737), which is higher than other ages (χ²=35.791, P<0.001); the high incidence season of NV virus is mainly winter, and the cumulative positive detection rate from October to December is 81.26% (529/651), higher than other seasons (χ²=173.426 , P<0.001), the high incidence season of RV virus is mainly spring and winter, the cumulative positive detection rate from November to March of the next year is 87.11% (642/737), higher than other seasons (χ²=252.628, P<0.001). Conclusion Spring and winter are the seasons of high incidence of viral diarrhea in children. Close monitoring of children under 2 years of age should be strengthened to prevent viral diarrhea early.