OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To investigate the diagnostic value of 62-slice spiral CT and its post-processing techniques for tibial plateau fracture(TPF)and its influence on treatment regimens selection.Methods A total of 173 TPF patients diagnosed and treated in our hospital from January 2021 to December 2022 were included,and the diagnostic accuracy,classification diagostic accuracy and fracture collapse degree accuracy of X-ray and CT scans were compared,with surgical and pathological diagnosis as the gold standard.Results CT and its post-processing technique can more clearly show the direction of fracture line,the displacement direction of fracture fragments and the collapse degree of articular surface than X-ray.The fracture morphology of 171 patients seen during the operation was consistent with CT and its post-processing images.The diagnostic accuracy of X-ray for TPF was 93.64%,which was lower than that of CT and its post-processing techniques(98.84% ),and the difference was statistically significant(χ2=6.474,P=0.011).The overall accuracy of X-ray in evaluating the degree of fracture collapse was significantly lower than that of CT 3D reconstruction(65.32% vs.90.75%;χ2=32.644,P<0.001).The total accuracy of CT and its post-processing techniques for TPF Schatzker classification(97.69% )was higher than that of X-ray(88.44% ),and the difference was statistically significant(χ2=11.462,P=0.001).Different CT reconstruction models had statistically significant difference on the total accuracy of TPF Schatzker classification diagnosis(χ2=40.647,P<0.001),and the diagnosis accuracy of volume reconstruction was the highest(96.53% ).Conclusion The application of CT and its post-processing techniques can effectively evaluate TPF,articular surface collapse and fracture classification,and provide imaging reference for clinical decision-making.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Objective: To evaluate the efficacy and prognosis of orthopedic surgical resection surgery in patients with newly diagnosed multiple myeloma (NDMM). Methods: This retrospective cohort study collected clinical data of patients with NDMM who underwent surgery due to spinal cord compression or pathological long-bone fractures at the Peking Union Medical College Hospital from 1 January 2003 to 31 December 2021. Patients who received biopsy or vertebroplasty/kyphoplasty were excluded and patients with the same degree of bone disease and who did not undergo any surgical intervention were selected as controls. Visual analogue scale (VAS) and physical status (ECOG) scores, progression-free survival (PFS), and overall survival (OS) were compared. Statistical analysis included the χ²-test, t-test, and Kaplan-Meier methods. Results: Baseline data were compared between the surgical group (n=40 with 43 interventions) and the non-surgical group (n=80), and included sex, age, paraprotein type, International Staging System (ISS), number of lytic lesions, cytogenetic abnormalities, first-line treatment, and the proportion of patients receiving autologous stem cell transplantation (ASCT) (all P>0.05). Serum M protein levels in the surgical group were significantly lower than those of the non-surgical group [(21.95±16.44) g/L vs. (36.18±20.85) g/L, P=0.005]. The surgical lesions involved the axial skeleton (79.1%, 34/43) or the extremities (20.9%, 9/43). VAS and ECOG scores improved significantly after surgery (VAS: 2.30±0.80 vs. 6.60±1.50, P<0.001; ECOG: 2.09±0.59 vs. 3.09±0.73, P<0.001). The median follow-up time was 51 months. Kaplan-Meier survival analysis suggested that the median PFS (25 vs. 29 months) and OS (46 vs. 60 months) were comparable between the surgical and non-surgical intervention groups (both P>0.05). Subgroup analysis showed that among patients with ISS Ⅰ or those who had received ASCT, PFS in the surgical group was similar to that of the non-surgical intervention group (both P>0.05), while OS was worse (P=0.005, 0.017). Patients with ISS Ⅱ/Ⅲ scores or without ASCT had similar PFS and OS between the surgical and non-surgical intervention groups (all P>0.05). Cox multivariate analysis suggested that ISS and ASCT were independent prognostic factors for OS (ISS: HR=0.42, 95%CI 0.19-0.93, P=0.031; ASCT: HR=0.41, 95%CI 0.18-0.97, P=0.041), while orthopedic surgery did not influence survival (P=0.233). Conclusion: For patients with NDMM, orthopedic surgical resection decreased bone-related complications and improved quality of life, but did not affect survival.
Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; Hematopoietic Stem Cell Transplantation/methods* ; Retrospective Studies ; Quality of Life ; Transplantation, Autologous ; Orthopedic Procedures ; Treatment Outcome

OBJECTIVE: The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population. METHODS: From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria. RESULTS: During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01). CONCLUSION NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.
Adult ; Aged ; Ankle Brachial Index ; Body Mass Index ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Incidence ; Lymphocytes/cytology* ; Male ; Middle Aged ; Neutrophils/cytology* ; Poisson Distribution ; Prospective Studies ; Vascular Diseases/etiology*

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca²⁺ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.
Animals ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Hearing ; Humans ; Mammals/metabolism* ; Mice ; Mice, Knockout ; Molecular Motor Proteins/metabolism*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases