Genotype-phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta.

PURPOSE: To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts. METHODS: A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts. RESULTS: A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts. CONCLUSION: The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.

Correlation of lipocalin 2 and glycolipid metabolism and body composition in a large cohort of children with osteogenesis imperfecta.

PURPOSE: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). METHODS: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. RESULTS: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-ß, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05). CONCLUSIONS: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta.

PURPOSE: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients. METHODS: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing. RESULTS: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = - 0.282), height Z score (r = - 0.292), ALP concentration (r = - 0.304), lumbar BMD (r = - 0.276), BMD Z score of the lumbar spine and femoral neck (r = - 0.32; r = - 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children. CONCLUSION: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.

The global burden of lymphoma: estimates from the Global Burden of Disease 2019 study.

OBJECTIVES: The aim of this study was to describe the global trends in the burden of lymphoma from 1990 to 2019. STUDY DESIGN: The data used in this study were from the Global Burden of Disease 2019 study. METHODS: This study described the age-standardised rates of incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lymphoma (non-Hodgkin and Hodgkin's lymphoma, NHL and HL, respectively) annually from 1990 to 2019, stratified by sociodemographic index (SDI) and 21 world regions. The estimated annual percentage changes in these indexes were calculated. RESULTS: In 2019, the age-standardised rates of HL per 100,000 population were lower than those of NHL in terms of incidence (1.1 vs 6.7 per 100,000 person-years, respectively) and prevalence (0.3 vs 5.7 per 100,000 person-years, respectively) but not mortality (21.6 vs 3.2 per 100,000 person-years, respectively). From 1999 to 2019, the global incidence of HL decreased and the incidence of NHL increased, and the prevalence of both HL and NHL increased, but the mortality rates decreased. When stratified by SDI, the incidence of HL decreased in all but middle-SDI regions, the mortality rate of HL decreased in all regions, and both the incidence and mortality rate of NHL increased in all but high-SDI regions. The prevalence of HL and NHL increased in all SDI regions, especially in middle-SDI regions. YLLs and DALYs of HL in all SDI regions and those of NHL in high-SDI regions decreased. YLDs slightly increased in middle- to high-SDI regions. CONCLUSIONS: Lymphoma remains a major public health issue, and better prevention, precise identification, and promising treatments are vitally important.

[Advances in the use of bevacizumab for the treatment of respiratory papilloma].

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

PTH level might be associated with impaired quality of life in patients with nonsurgical hypoparathyroidism.

OBJECTIVE: Nonsurgical hypoparathyroidism (ns-HP) is a rare disease. There are few studies on Quality of Life (QoL) among patients with ns-HP. This study aimed to investigate the QoL among ns-HP patients with regular conventional treatment, and explore the influence factors affecting QoL among these Chinese ns-HP patients. METHODS: This is a cross-sectional study comparing 101 patients identified as ns-HP and 101 healthy controls. The questionnaires of Short Form 36 Health Survey questionnaire version 2(SF-36v2) were used to evaluate QoL. RESULTS: Scores of all eight subdomains of SF-36v2 and physical component scores (PCS), mental component scores (MCS) were significantly lower in the ns-HP group compared with the healthy controls. The indices of all subdomains of SF-36v2 between Q1 (the lowest quartile) and Q4 (the highest quartile) groups were compared, suggesting higher percentages of detectable parathyroid hormone (PTH) before treatment in Q4 group among all QoL indices except two subdomains (physical function and body pain). CONCLUSION: Both mental and physical QoL were impaired in the ns-HP patients even with regular conventional treatment for hypocalcemia, which were more severe in cases with lower baseline PTH levels.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

[The 499th case: Roux-en-Y gastric bypass, limb weakness, and ostealgia].

A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain mediators including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores of the study group and the control group before treatment were 7.94±0.76 and 8.20±0.81, and PSQI scores were 16.84±3.90 and 16.29±3.84, respectively, with no statistically significant differences (both P>0.05). After 4 weeks of treatment, the VAS scores of the two groups were 2.84±0.80 and 3.35±0.87, and PSQI scores were 6.78±1.90 and 7.98±2.40, respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). There were no significant differences of the serum levels of NPY, PGE2, SP and ß-endorphin before treatment in the study group and control group (all P>0.05). After 4 weeks of treatment, the levels of NPY, PGE2, SP and ß-Endorphin in the study group were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group, respectively. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain intensity and sleep quality of patients with severe thoracic PHN and reduce the levels of pain mediators, with a high safety profile.

[Efficacy and safety of high-voltage pulsed radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia].

Objective: To investigate the efficacy and safety of high-voltage pulse radiofrequency combined with pregabalin on severe thoracic postherpetic neuralgia (PHN). Methods: A total of 103 patients with PHN who were admitted to the Department of Pain Medicine of Henan Provincial People's Hospital from May 2020 to May 2022 were retrospectively selected, including 50 males and 53 females, and aged 40 to 79 (65.4±9.2) years. The patients were divided into two groups according to the treatment methods they received: the control group (n=51) and the study group (n=52). The patients in the control group were treated with oral pregabalin, and the patients in the study group received pregabalin plus high-voltage pulse radiofrequency therapy. The pain intensity and efficacy of the two groups were evaluated before treatment and 4 weeks after treatment. The pain intensity, the sleep quality and the efficacy of treatment was evaluated by visual analogue scale (VAS) score, Pittsburgh Sleep Quality Index (PSQI) score and nimodipine method, respectively. The levels of pain factors including serum neuropeptide Y (NPY), prostaglandin E2 (PGE2), substance P (SP) and ß-Endorphin were measured. The differences of the above indicators and the incidence of adverse reactions were compared between the two groups. Results: The VAS scores and PSQI scores of the study group and the control group before treatment were (7.94±0.76), (8.20±0.81), (16.84±3.90) and (16.29±3.84), respectively, with no statistically significant difference (both P>0.05). After 4 weeks of treatment, the VAS scores and PSQI scores of the two groups were (2.84±0.80), (3.35±0.87), (6.78±1.90) and (7.98±2.40), respectively, and the VAS score and PSQI score in the study group were lower than those in the control group (both P<0.05). Serum levels of NPY, PGE2, SP and ß-Endorphin were (298.5±31.0) ng/L, (92.3±11.0) µg/L, (156.8±21.4) ng/L, and (8.6±1.6) ng/L in the study group and (304.2±28.6) ng/L, (94.4±12.9) µg/L, (152.7±23.8) ng/L and (8.2±1.8) ng/L in the control group, with no significant differences (all P>0.05). After 4 weeks of treatment, levels of NPY, PGE2, SP and ß-Endorphin were (240.7±26.8) ng/L, (74.4±8.6) µg/L, (108.9±15.7) ng/L and (4.4±0.9) ng/L, which were lower than those in the control group [(268.1±29.4) ng/L, (79.7±8.3) µg/L, (115.2±16.2) ng/L, (5.2±1.3) ng/L, respectively], with statistically significant differences (all P<0.05). After treatment, 29 cases were cured, 16 cases were markedly effective and 6 cases were effective in the study group, while 16 cases, 24 cases and 8 cases were cured, markedly effective and effective in the control group. The overall efficacy of patients in the study group was better than that in the control group (Z=-2.32, P=0.018). The incidence of adverse reactions in the study group and control group was 11.5% (6/52) and 7.8% (4/51), respectively, with no statistically significant difference (χ2=0.40, P=0.527). Conclusion: High-voltage pulse radiofrequency combined with pregabalin can significantly improve the pain and sleep quality of patients with severe thoracic PHN and reduce the level of pain factors, with a high safety profile.

[Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia].

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

[Urban-rural disparities of depression symptoms and its influencing factors among the elderly aged ≥65 years old in Anhui Province from 2019 to 2020].

Objective: To analyze the difference in depression symptoms and influencing factors between urban and rural elderly people aged ≥65 years old in Anhui Province. Methods: Based on the data from a survey of 68 communities in Anhui Province that implemented the National Elderly Psychological Care Project from 2019 to 2020, the current status of depression symptoms in the elderly was evaluated using the Patient Health Questionnaire-9 (PHQ-9). The difference in the detection rate of depression symptoms between urban and rural elderly people with different characteristics was compared by using the χ2 test. The logistic regression model was used to analyze the relevant factors of depression symptoms in urban and rural elderly people. Results: A total of 15 532 elderly people aged≥65 years old were included in the survey. The detection rate of depressive symptoms was 7.12%, which was higher in rural areas (9.08%) than in urban areas (6.48%). Logistic regression showed that chronic diseases were risk factors for depressive symptoms in elderly people from both urban and rural areas. Positive attitudes towards aging and good mental resilience were protective factors for depressive symptoms in elderly people. Having hobby (OR=0.64, 95%CI: 0.45-0.91), good relationship with children (OR=0.56, 95%CI: 0.41-0.76), good relationship with spouse (OR=0.51, 95%CI: 0.37-0.71), and having at least 6 friends (OR=0.48, 95%CI: 0.32-0.71) were the protective factors for depressive symptoms in urban elderly people. A good relationship with neighbors (OR=0.58, 95%CI: 0.41-0.82) and having 1-2 friends (OR=0.40, 95%CI: 0.25-0.64) were the protective factors for depressive symptoms in rural elderly people. Women (OR=1.49, 95%CI: 1.06-2.10) and higher education level (OR=1.81, 95%CI: 1.19-2.74, compared with illiterate/semi-illiterate in primary school; OR=2.94, 95%CI: 1.82-4.76, compared with illiterate/semi-illiterate in junior high school and above) were the risk factors for depressive symptoms in rural elderly people. Conclusion: There are differences between urban and rural areas in depressive symptoms among elderly people in Anhui Province. The detection rate of depression symptoms among rural elderly people is higher, and the influencing factors of depressive symptoms between urban and rural elderly people are also different, which should be treated specifically in the implementation of intervention measures.

[Clinicopathological features of rectal adenocarcinoma with enteroblastic differentiation].

Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.

[Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis].

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

[Clinical characteristics and molecular mechanisms of hypoparathyroidism related to GATA3 gene mutation].

Objective: To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation. Methods: A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms. Results: The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG). Conclusions: Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.

[The relationship between insulin resistance and risk of long-term mortality in people without diabetes: a 30-year follow-up of the Daqing Diabetes Study].

Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95%CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status (HR=1.97,95%CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders (HR=1.22, 95%CI 1.08-1.39, P=0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

[Clinical analysis of 5 cases of dermatomyositis complicated with macrophage activation syndrome].

To investigate the clinical and immunological features of dermatomyositis (DM) complicated with macrophage activation syndrome (MAS). The demographic and clinical characteristics of five patients diagnosed with DM complicated with MAS hospitalized in the Department of Rheumatology and Immunology, Peking University People ' s Hospital from 2011 to 2021 were collected. The results of clinical manifestations, laboratory tests, immunological features, treatments and prognosis were analyzed and summarized. In this study, five female patients in Peking University People's Hospital with an average age of 63.8 (44.0-83.0) years and an average disease duration of 16.1 (1.5-48.0) months. All the patients had typical DM rash (such as heliotrope sign, V/shawl sign or Gottron's sign/papules). They all had muscle involvement (including myalgia or muscle weakness). Two patients had positive myositis-specific antibodies (MSAs), in which case 1 had anti-TIF1-γ antibody and case 5 had anti-NXP-2 antibody. Four patients had interstitial lung disease except case 3. All of the cases developed MAS in the active stage of DM. Common manifestations of MAS in these five patients included high-grade fever, cytopenia, decreased fibrinogen, elevated ferritin and increased soluble CD25. Case 1 presented with neutropenia (0.6×109 /L), thrombocytopenia (26.0×109 /L), hypofibrinogenemia (0.9 g/L), markedly elevated ferritin (26 331.0 µg/L), decreased NK cell activity. Case 2 had anaemia (hemoglobin 81.0 g/L), thrombocytopenia (55.0×109 /L), hypertriglyceridemia (4.7 mmol/L), hypofibrinogenemia (1.2 g/L), elevated ferritin (>100 000.0 µg/L), hemophagocytosis in bone marrow. Case 3 had anaemia (hemoglobin 88 g/L), decreased fibrinogen (1.9 g/L), increased ferritin (>27 759.0 µg/L), splenomegaly, hemophagocytosis in bone marrow. Case 4 suffered from neutropenia(0.3×109 /L), anaemia(hemoglobin 78 g/L), hypertriglyceridemia (4.2 mmol/L), hypofibrinogenemia (0.9 g/L), increased ferritin (>100 000.0 µg/L), and decreased NK cell activity. Case 5 presented anaemia (hemoglobin 60.0 g/L), thrombocytopenia (67.0×109 /L), hypertriglyceridemia (12.7 mmol/L), decreased fibrinogen (1.1 g/L), and elevated ferritin (>923.0 µg/L). All the patients were treated with methylprednisone pulse therapy (200-500 mg) combined with cyclosporine while case 5 received rituximab after methylprednisone pulses. In addition, case 3 also received the combination of mycophenolate mofetil. Case 1 was given etoposide while case 4 was treated with cyclophosphamide and repeated plasmapheresis at the same time. Moreover, intravenous immunoglobulin was added meantime apart from case 3. The condition of four patients improved significantly, nevertheless case 4 experienced recurred pulmonary symptoms and died of respiratory failure. As for complications about infection, case 2 had bacterial infection with high level procalcitonin (PCT) before MAS treatment and condition was improved after empiric antibacterial therapy. Case 3 had cytomegalovirus DNAemia before diagnosis of MAS and viral titer turned negative after ganciclovir therapy. After treatment of MAS, four patients developed cytomegalovirus DNAemia except case 3, in which case 5 was co-infected with bacteria. To sum, DM complicated with MAS is relatively rare, and its patients are of ten in life-threatening condition. Early detection, treatment and prevention of infection during treatment are critical to improve the prognosis.