ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Objective:To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients.Methods:In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children′s Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated.Results:Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed.Conclusion:Burosumab can improve clinical symptoms in children with XLH with a good safety profile.

OBJECTIVE: To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. METHODS: Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. RESULTS: Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. CONCLUSION FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.
Humans ; Child ; Glucocorticoids/therapeutic use* ; Receptor, Melanocortin, Type 2/genetics* ; Retrospective Studies ; Adrenal Insufficiency/genetics* ; Mutation

The article reports a rare case of isolated persistent left superior vena cava (PLSVC) found during the catheterization of a dialysis catheter in an end-stage renal disease patient and the occurrence of guidewire entrapment in Chiari net. The patient was scheduled to have emergency dialysis due to end-stage renal disease and acute left heart failure. And a tunnel-cuffed catheter (TCC) for dialysis insertion was planned. Isolated PLSVC was found firstly by the imaging process. Then the guidewire was entrapped at the right atrium in the further operation. During the operation of the guidewire, the guidewire loosened and withdrawn with a fine fiber, which was considered a possibility of Chiari net. In the follow-up after one week, the TCC worked well, and the heart function improved after dialysis.

Renal replacement therapy and perioperative management have difficulties in hemophilia patients with end-stage renal disease. The paper summarized the diagnosis and treatment experience of six hemophilia patients complicated with end-stage renal disease from January 1, 2000 to March 31, 2023 in Peking Union Medical College Hospital. Among 6 patients treated with peritoneal dialysis, 3 were treated with hemodialysis or continuous venous-venous hemodialysis. Altogether 11 dialysis access procedures were conducted successfully, and no serious bleeding or thrombotic events. In further conjunction with literature review, the paper summarized the key points of dialysis access appliance relevant to such patients, to provide reference for renal replacement treatment paths.

Objective:To explore the correlation of psychological capital, role stress and readiness for interprofessional learning in clinical nurses.Methods:From January to February 2021, convenience sampling was used to select 524 clinical nurses from four hospitals in Henan Province as the research object. The investigation was carried out with the Psychological Capital Questionnaire, Role Stress Scale and the Readiness for Interprofessional Learning Scale. AMOS 24.0 software was used for mediation effect analysis and structural equation modeling. A total of 524 questionnaires were distributed, and 523 valid questionnaires were recovered, with a valid recovery rate of 99.8%.Results:Among 523 clinical nurses, the total scores of the Psychological Capital Questionnaire, Role Stress Scale and the Readiness for Interprofessional Learning Scale were (89.11±14.18) , (36.15±10.30) and (74.61±8.24) , respectively. The psychological capital of clinical nurses was positively correlated with readiness for interprofessional learning ( r=0.53, P<0.001) , while role stress was negatively correlated with psychological capital and readiness for interprofessional learning ( r=-0.43, -0.13; P<0.001) . Role pressure could directly affect readiness for interprofessional learning. Psychological capital could directly affect readiness for interprofessional learning, and it could also indirectly affect clinical nurses' readiness for interprofessional learning through role stress, with a mediating effect of 81.67%. Conclusions:Nursing managers should continuously monitor the psychological capital of clinical nurses, and improve clinical nurses' readiness for interprofessional learning through effective management measures and positive psychological interventions, and promote multidisciplinary cross-cooperative learning.

Background Procymidone (PCM) exposure can cause damage to reproductive organs of male mice, but whether its mechanism is related to the retinoic acid (RA) signaling pathway is unclear. Objective To explore the possible mechanism of PCM-induced testes damage in adolescent mice. Methods Three-week-old ICR mice (n=64) were randomly divided into a control group and three dose groups (low, medium, and high), with 16 mice in each group. PCM was administered orally at 0, 50, 100, and 200 mg·kg⁻¹·d⁻¹ for 21 consecutive days. Serum and bilateral testes in each mouse were collected to detect content of testosterone in serum and to observe histological changes in testis section after the mice were sacrificed one week after cessation of drug administration. Real-time fluorescence quantitative PCR and Western blotting were used to detect the mRNA expression abundances of genes related to the RA signaling pathway and apoptosis genes Casp9 and Casp12, and the protein expression levels of CYP26A1, ALDH2, and CASP9 respectively. Results Compared with the control group, there was no significant change in the overall appearance and testicular appearance of mice in each dose group after the PCM exposure. According to pathological section observation, the testicular seminiferous tubules of mice in the low-dose group showed slight atrophy and reduced sperm production; the testes of mice in the medium- and the high-dose groups showed obvious pathological damage (e.g. dilated lumen of seminiferous tubules, damaged spermatogenic epithelium, decreased number of spermatogonia, and partial absence of sertoli cells); as the concentration of PCM increased, the degree of spermatogenic epithelial damage in mice gradually increased and the number of spermatozoa in the seminiferous tubules decreased. There were no significant differences in the distance between the anus and the genitals, testicular mass, testicular volume, and testicular organ coefficient among the four groups of mice (P>0.05). The body weights of the mice in the low-, medium-, and high-dose groups were (34.91±1.89), (34.88±1.75), and (32.94±1.37) g respectively, and that in the high-dose group was lower than that in the control group, (35.93±1.99) g, (P<0.05); the serum testosterone concentrations were (313.77±5.32), (305.31±3.47), and (304.80±5.28) pg·mL⁻¹ respectively, which were lower than that in the control group, (319.05±1.92) pg·mL⁻¹ (P<0.05); as the dose of PCM increased, the body weight and serum testosterone concentration showed decreasing trends. The mRNA expression levels of Stra6 and Rbp1 in the high-dose group were higher than those in the control group (P<0.05); the mRNA expression levels of Aldh2, Aldh1a1, Aldh1a3, Rarα, Rar\begin{document}$\beta $\end{document}, Rxrα and Rxr\begin{document}$\beta $\end{document} in the medium-and the high-dose groups were higher than those in the control group (P<0.05); the mRNA expression levels of Cyp26a1 and Cyp26b1 in the medium- and high-dose groups were lower than those in the control group(P<0.05); the mRNA expression levels of apoptosis genes Casp9 and Casp12 in the medium-and the high-dose groups were higher than those in the control group (P<0.05). The protein expression level of CYP26A1 in each exposure group was lower than that in the control group (P<0.05), and the expression level decreased with increasing concentration of PCM; the expression level of ALDH2 protein in the medium- and the high-dose groups and the protein expression level of CASP9 in each exposure group were higher than those in the control group (P<0.05), and the levels increased with increasing concentration of PCM. Conclusion PCM can damage the testis tissues of adolescent mice, where RA signaling pathway, Casp9 and Casp12 genes, and CASP9 protein are activated.

Objective To explore the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis(NEC).Methods A retrospective study was carried out in the infants with NEC admitted to 6 cooperative hospitals in Guangdong Province between January 2005 and December 2014.The clinical features and risk factors of poor prognosis in preterm and full-term infants diagnosed NEC,early onset and late onset NEC were analyzed.Results A total of 449 cases who met the criteria were admitted during the study time.The mortality was 23.6％ (106/449 cases),of which the preterm group was 24.6％ (58/238 cases) while the full-term group was 22.7％ (48/211 cases),the early onset group was 22.1％ (45/204 cases) while the late onset group was 24.3％ (57/235 cases).The median number of NEC onset in preterm group was 11 d after birth while the number of the full-term group was 6 d.Full-term infants who diagnosed NEC were more likely to manifest themselves as abdominal distension (52.1％ vs.42.0％,x2 =4.597,P =0.032),vomiting(36.5％ vs.17.2％,x2 =21.428,P =0.000) and bloody stool(30.3％ vs.21.4％,x2 =4.653,P =0.031);but in the onset of NEC,preterm infants more likely to have feeding intolerance (21.0％ vs.12.8％,x2=5.309,P =0.021).The early onset group of full-term NEC was much common in twins or multiplets(9.4％ vs.1.1％,x2 =6.226,P =0.013),which rate of surgical therapy was much higher (41.0％ vs.27.0％,P =0.036) and the breast-feeding rate before NEC was lower than the late onset group(14.5％ vs.32.6％,x2 =9.500,P =0.002),the differences were statistically significant.The gestational age and birth weight were bigger in the early onset group of preterm NEC[(33.8 ±2.5) weeks vs.(32.2 ±2.8) weeks,t =4.261,P =0.000;(2.1 ±0.5) kg vs.(1.7 ± 0.5) kg,t =4.735,P =0.000)],but length of stay was shorter than the late onset group (18.0 d vs.26.5 d,P =0.000).Logistic regression analysis showed that the risk factors of poor prognosis of full-term NEC were shock,peritonitis and sepsis;while risk factors of poor prognosis of preterm NEC were small for gestational age infant,pulmonary hemorrhage,shock,intestinal perforation and sepsis;the risk factors of poor prognosis of the early onset group of full-term NEC was shock;while those of the late onset group were shock and peritonitis;the risk factors of poor prognosis in the early onset group of preterm NEC were shock and sepsis,while those in the late onset group were pulmonary hemorrhage,shock,intestinal perforation and sepsis.Conclusions Compared to the preterm NEC,the onset time of full-term NEC was earlier and the clinical manifestations were more typical.Early identification and management of shock,peritonitis,intestinal perforation,sepsis and pulmonary hemorrhage can reduce the risk of poor prognosis of neonate NEC.