Simulator Verification Is Potentially Beneficial for the Fitting of Softband Bone Conduction Hearing Devices in Young Children.

HYPOTHESIS: The current study employed a skull-simulator verification method to assess whether the output of softband bone conduction hearing devices (BCHDs) at the manufacturer's default settings deviated widely from the target determined by the fitting formula. BACKGROUND: Real ear analysis is utilized for the verification of the fitting of air conduction hearing devices (ACHDs) in a variety of institutions. This procedure, however, has not been used in the fitting of BCHDs, largely due to the difficulty of testing the output of these devices to temporal bones. Despite the availability of skull simulators, they have not been utilized clinically to measure BCHD output. MATERIALS AND METHODS: This prospective, single-center study enrolled 42 subjects, aged 3 months to 10 years, with microtia-atresia-associated mild-to-severe bilateral conductive hearing loss. Hearing sensitivity was evaluated behaviorally by pure tone audiometry (PTA) in 22 subjects 4 years or older (the PTA group), and by auditory brainstem response (ABR) in 20 subjects younger than 4 years (the ABR group). Following 6 months of subjects wearing the prescribed softband BCHDs, their dial level (DL) thresholds were reassessed while using their own BCHDs, configured with zero gain across all frequencies, functioning solely as a bone vibrator. These DL thresholds were inputted into the fitting formula, desired sensation level-bone conduction devices (DSL-BCD) for children, to obtain the target values of BCHD output. The simulator output of the BCHD programmed at the manufacturer's default setting was measured in response to speech presented at 55, 65, and 80 dB SPL, followed by gain adjustment based on the differences between the simulator output and the target. Aided speech intelligibility index (SII) was measured before and after the gain adjustment. RESULTS: The softband BCHDs at the manufacturer's settings generally had lower output than the prescribed target values. This difference was larger at low frequencies and low levels. Across the 12 points tested (four frequencies from 500 to 4000 Hz multiplied by three levels), 22 (52.3%) and 42 (100%) BCHDs had deviations of +7 and +5 dB, respectively, at one point or more. The gain adjustments reduced the deviation and improved the SII values at the two lower levels of speech presented. CONCLUSION: The simulator output of softband bone conduction hearing devices (BCHDs) with the manufacturer's settings may exhibit significant deviations from the formula. Objective output verification should be considered a beneficial step in BCHD fitting and is recommended when applicable.

Optimizing Paclitaxel Oral Absorption and Bioavailability: TPGS Co-Coating via Supercritical Anti-Solvent Fluidized Bed Technology.

Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.

Synthesis of 2D layered transition metal (Ni, Co) hydroxides via edge-on condensation.

Layered transition metal hydroxides (LTMHs) with transition metal centers sandwiched between layers of coordinating hydroxide anions have attracted considerable interest for their potential in developing clean energy sources and storage technologies. However, two-dimensional (2D) LTMHs remain largely understudied in terms of physical properties and applications in electronic devices. Here, for the first time we report > 20 µm α-Ni(OH)2 2D crystals, synthesized from hydrothermal reaction. And an edge-on condensation mechanism assisted with the crystal field geometry is proposed to understand the 2D intra-planar growth of the crystals, which is also testified through series of systematic comparative studies. We also report the successful synthesis of 2D Co(OH)2 crystals (> 40 µm) with more irregular shape due to the slightly distorted octahedral geometry of the crystal field. Moreover, the detailed structural characterization of synthesized α-Ni(OH)2 are performed. The optical band gap energy is extrapolated as 2.54 eV from optical absorption measurements and the electronic bandgap is measured as 2.52 eV from reflected electrons energy loss spectroscopy (REELS). We further demonstrate its potential as a wide bandgap (WBG) semiconductor for high voltage operation in 2D electronics with a high breakdown strength, 4.77 MV/cm with 4.9 nm thickness. The successful realization of the 2D LTMHs opens the door for future exploration of more fundamental physical properties and device applications.

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/ß-Catenin Pathway.

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.

A reporter gene assays for bioactivity determination of human chorinonic gonadotropin / 药学学报

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine.

The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0→∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.

Application and evaluation of surgical tool and tool tip recognition based on Convolutional Neural Network in multiple endoscopic surgical scenarios.

BACKGROUND: In recent years, computer-assisted intervention and robot-assisted surgery are receiving increasing attention. The need for real-time identification and tracking of surgical tools and tool tips is constantly demanding. A series of researches focusing on surgical tool tracking and identification have been performed. However, the size of dataset, the sensitivity/precision, and the response time of these studies were limited. In this work, we developed and utilized an automated method based on Convolutional Neural Network (CNN) and You Only Look Once (YOLO) v3 algorithm to locate and identify surgical tools and tool tips covering five different surgical scenarios. MATERIALS AND METHODS: An algorithm of object detection was applied to identify and locate the surgical tools and tool tips. DarkNet-19 was used as Backbone Network and YOLOv3 was modified and applied for the detection. We included a series of 181 endoscopy videos covering 5 different surgical scenarios: pancreatic surgery, thyroid surgery, colon surgery, gastric surgery, and external scenes. A total amount of 25,333 images containing 94,463 targets were collected. Training and test sets were divided in a proportion of 2.5:1. The data sets were openly stored at the Kaggle database. RESULTS: Under an Intersection over Union threshold of 0.5, the overall sensitivity and precision rate of the model were 93.02% and 89.61% for tool recognition and 87.05% and 83.57% for tool tip recognition, respectively. The model demonstrated the highest tool and tool tip recognition sensitivity and precision rate under external scenes. Among the four different internal surgical scenes, the network had better performances in pancreatic and colon surgeries and poorer performances in gastric and thyroid surgeries. CONCLUSION: We developed a surgical tool and tool tip recognition model based on CNN and YOLOv3. Validation of our model demonstrated satisfactory precision, accuracy, and robustness across different surgical scenes.

lmo4a Contributes to Zebrafish Inner Ear and Vestibular Development via Regulation of the Bmp Pathway.

BACKGROUND: In vertebrates, the development of the inner ear is a delicate process, whereas its relating molecular pathways are still poorly understood. LMO4, an LIM domain-only transcriptional regulator, is drawing an increasing amount of interest for its multiple roles regarding human embryonic development and the modulation of ototoxic side effects of cisplatin including cochlear apoptosis and hearing loss. The aim of the present study is to further explore the role of lmo4a in zebrafish inner ear development and thus explore its functional role. METHODS: The Spatial Transcript Omics DataBase was referred to in order to evaluate the expression of lmo4a during the first 24 h of zebrafish development. In situ hybridization was applied to validate and extend the expression profile of lmo4a to 3 days post-fertilization. The morpholino (MO) knockdown and CRISPR/Cas9 knockout (KO) of lmo4a was applied. Morphological analyses of otic vesical, hair cells, statoacoustic ganglion and semicircular canals were conducted. The swimming pattern of lmo4a KO and MO zebrafish was tracked. In situ hybridization was further applied to verify the expression of genes of the related pathways. Rescue of the phenotype was attempted by blockage of the bmp pathway via heat shock and injection of Dorsomorphin. RESULTS: lmo4a is constitutively expressed in the otic placode and otic vesicle during the early stages of zebrafish development. Knockdown and knockout of lmo4a both induced smaller otocysts, less hair cells, immature statoacoustic ganglion and malformed semicircular canals. Abnormal swimming patterns could be observed in both lmo4a MO and KO zebrafish. eya1 in preplacodal ectoderm patterning was downregulated. bmp2 and bmp4 expressions were found to be upregulated and extended in lmo4a morphants, and blockage of the Bmp pathway partially rescued the vestibular defects. CONCLUSIONS: We concluded that lmo4a holds a regulative effect on the Bmp pathway and is required for the normal development of zebrafish inner ear. Our study pointed out the conservatism of LMO4 in inner ear development between mammals and zebrafish as well as shed more light on the molecular mechanisms behind it. Further research is needed to distinguish the relationships between lmo4 and the Bmp pathway, which may lead to diagnostic and therapeutic approaches towards human inner ear malformation.

vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway.

Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to the pathogenesis of HFM is largely unknown. Here, we sought to elucidate the effects of the VWA1 mutation at the molecular level by generating a vwa1-knockout zebrafish line using CRISPR/Cas9. Mutants and crispants showed cartilage dysmorphologies, including hypoplastic Meckel's cartilage and palatoquadrate cartilage, malformed ceratohyal with widened angle, and deformed or absent ceratobranchial cartilages. Chondrocytes exhibited a smaller size and aspect ratio and were aligned irregularly. In situ hybridization and RT-qPCR showed a decrease in barx1 and col2a1a expression, indicating abnormal cranial neural crest cell (CNCC) condensation and differentiation. CNCC proliferation and survival were also impaired in the mutants. Expression of FGF pathway components, including fgf8a, fgfr1, fgfr2, fgfr3, fgfr4, and runx2a, was decreased, implying a role for VWA1 in regulating FGF signaling. Our results demonstrate that VWA1 is essential for zebrafish chondrogenesis through effects on condensation, differentiation, proliferation, and apoptosis of CNCCs, and likely impacts chondrogenesis through regulation of the FGF pathway.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study.

BACKGROUND: The options for first-line treatment of advanced oesophageal squamous cell carcinoma are scarce, and the outcomes remain poor. The anti-PD-1 antibody, tislelizumab, has shown antitumour activity in previously treated patients with advanced oesophageal squamous cell carcinoma. We report interim analysis results from the RATIONALE-306 study, which aimed to assess tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma. METHODS: This global, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 study was conducted at 162 medical centres across Asia, Europe, Oceania, and North America. Patients (aged ≥18 years) with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma (regardless of PD-L1 expression), Eastern Cooperative Oncology Group performance status of 0-1, and measurable or evaluable disease per Response Evaluation Criteria in Solid Tumours (version 1.1) were recruited. Patients were randomly assigned (1:1), using permuted block randomisation (block size of four) and stratified by investigator-chosen chemotherapy, region, and previous definitive therapy, to tislelizumab 200 mg or placebo intravenously every 3 weeks on day 1, together with an investigator-chosen chemotherapy doublet, comprising a platinum agent (cisplatin 60-80 mg/m2 intravenously on day 1 or oxaliplatin 130 mg/m2 intravenously on day 1) plus a fluoropyrimidine (fluorouracil [750-800 mg/m2 intravenously on days 1-5] or capecitabine [1000 mg/m2 orally twice daily on days 1-14]) or paclitaxel (175 mg/m2 intravenously on day 1). Treatment was continued until disease progression or unacceptable toxicity. Investigators, patients, and sponsor staff or designees were masked to treatment. The primary endpoint was overall survival. The efficacy analysis was done in the intention-to-treat population (ie, all randomly assigned patients) and safety was assessed in all patients who received at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03783442. FINDINGS: Between Dec 12, 2018, and Nov 24, 2020, 869 patients were screened, of whom 649 were randomly assigned to tislelizumab plus chemotherapy (n=326) or placebo plus chemotherapy (n=323). Median age was 64·0 years (IQR 59·0-69·0), 563 (87%) of 649 participants were male, 86 (13%) were female, 486 (75%) were Asian, and 155 (24%) were White. 324 (99%) of 326 patients in the tislelizumab group and 321 (99%) of 323 in the placebo group received at least one dose of the study drug. As of data cutoff (Feb 28, 2022), median follow-up was 16·3 months (IQR 8·6-21·8) in the tislelizumab group and 9·8 months (IQR 5·8-19·0) in the placebo group, and 196 (60%) of 326 patients in the tislelizumab group versus 226 (70%) of 323 in the placebo group had died. Median overall survival in the tislelizumab group was 17·2 months (95% CI 15·8-20·1) and in the placebo group was 10·6 months (9·3-12·1; stratified hazard ratio 0·66 [95% CI 0·54-0·80]; one-sided p<0·0001). 313 (97%) of 324 patients in the tislelizumab group and 309 (96%) of 321 in the placebo group had treatment-related treatment-emergent adverse events. The most common grade 3 or 4 treatment-related treatment-emergent adverse events were decreased neutrophil count (99 [31%] in the tislelizumab group vs 105 [33%] in the placebo group), decreased white blood cell count (35 [11%] vs 50 [16%]), and anaemia (47 [15%] vs 41 [13%]). Six deaths in the tislelizumab group (gastrointestinal and upper gastrointestinal haemorrhage [n=2], myocarditis [n=1], pulmonary tuberculosis [n=1], electrolyte imbalance [n=1], and respiratory failure [n=1]) and four deaths in the placebo group (pneumonia [n=1], septic shock [n=1], and unspecified death [n=2]) were determined to be treatment-related. INTERPRETATION: Tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy. Given that the interim analysis met its superiority boundary for the primary endpoint, as confirmed by the independent data monitoring committee, this Article represents the primary study analysis. FUNDING: BeiGene.

Supercritical fluid coating of flavonoids on excipients enhances drug release and antioxidant activity.

Supercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles. The results showed that temperature, pressure, carrier, and drug solution concentration have a large effect on yield. Within the study range, low supercritical CO2 density at higher temperature and lower pressure, a larger surface area carrier, and moderate drug solution concentration led to a higher yield. The effect of the solvent on the yield of flavonoids is a result of multiple factors. Scanning electron microscopy (SEM) images showed that the drug-loaded particles prepared from different carriers and solvents have different precipitations pattern on the carrier surface, and their particle sizes were smaller than unprocessed particles and those prepared by the SAS process. Fluorescence microscopy (FM) results showed that the flavonoids were uniformly coated on the carrier. X-ray powder diffraction (XRPD) results showed that the crystalline morphology of SAS-FB particles remained unchanged after the SAS-FB process, although the diffraction peak intensity decreased. The cumulative dissolution of SAS-FB particles was more than four times faster in the first 5 min than that of the unprocessed flavonoids. The antioxidant activity of SAS-FB processed LUT, NGR and DMY was 1.89-3.78 times, 4.92-10.68 times and 0.99-2.57 times higher than that of the untreated flavonoids, respectively. The approach provides a reference for the application of SAS-FB technology in flavonoids.

Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high-fat diet.

Aging-associated microbial dysbiosis exacerbates various disorders and dysfunctions, and is a major contributor to morbidity and mortality in the elderly, but the underlying cause of this aging-related syndrome is confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging and succumb to death by 4 weeks, and are therefore useful as a premature aging research model. Here, fecal microbiota transplantation from SIRT6 KO mice into wild-type (WT) mice phenocopies the gut dysbiosis and premature aging observed in SIRT6 KO mice. Conversely, an expanded lifespan was observed in SIRT6 KO mice when transplanted with microbiota from WT mice. Antibiotic cocktail treatment attenuated inflammation and cell senescence in KO mice, directly suggesting that gut dysbiosis contributes to the premature aging of SIRT6 KO mice. Increased Enterobacteriaceae translocation, driven by the overgrowth of Escherichia coli, is the likely mechanism for the premature aging effects of microbiome dysregulation, which could be reversed by a high-fat diet. Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high-fat diet for correcting gut dysbiosis and alleviating premature aging. This study provides a rationale for the integration of microbiome-based high-fat diets into therapeutic interventions against aging-associated diseases.

The association of air pollutants with hospital outpatient visits for child and adolescence psychiatry in Shenzhen, China.

BACKGROUND: Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. METHODS: A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO2, PM2.5, SO2 and O3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. RESULT: A total of 94,660 cases aged 3-18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M0) showed that in the single lag effect result, when the average daily concentration of NO2 at 24 µg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO2 M0 value to the outpatient visits were 1.438 (1.137-1.818) over lag 0-2, 1.454 (1.120-1.887) over lag 0-3, 1.466 (1.084-1.982) over lag 0-4, 1.680 (1.199-2.354) over lag 0-5, 1.993 (1.369-2.903) over lag 0-6, and 2.069 (1.372-3.119) over lag 0-7. However, PM2.5, SO2, O3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO2 increases by 10 units or when the maximum concentration of NO2 is reached. CONCLUSION: Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP.

Surgical outcome and safety of peripheral iridectomy plus goniosynechialysis and goniotomy in the treatment of advanced primary angle-closure glaucoma / 中华实验眼科杂志

Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.

A case of Acromicric dysplasia with FBN1 mutation / 中华内分泌代谢杂志

Acromicric dysplasia(AD) is a rare skeletal dysplasia characterized by severe short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and radiological characteristics. The clinical data and genetic test results of one patient with AD in our hospital were analyzed, and the clinical characteristics of this case were summarized. The main manifestations of the child were short stature, short hands and feet, mild facial dysmorphism, short and stubby metacarpals and phalanges on hand X-ray. One mutation, FBN1: c.5141T>G(p.Met1714Arg), was identified in this child, the mutation is inherited from her short mother and grandfather. AD is a rare congenital skeletal dysplasia disorder associated with mutations in the FBN1 gene. It conforms to the pathogenesis of autosomal dominant genetic disease.

2023 China Guidelines for Lipid Management / 老年心脏病学杂志（英文版）

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise.@*METHODS@#A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated.@*RESULTS@#After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01).@*CONCLUSION@#Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Collaborative study to evaluate a reporter gene assay for recombinant human follicle-stimulating hormone bioactivity / 药学学报

The goal of this work was to explore the prospect of standardized application of an in-vitro bioactivity assay for recombinant human follicle-stimulating hormone based on a reporter gene. The relative accuracy, intermediate precision, linearity and applicable range of the method were validated according to the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Three laboratories used this method to determine the in-vitro biological activities of six batches of drug product and three batches of drug substance manufactured by two different companies. The consistency of the potency determined by three laboratories, the intra-laboratory precision and inter-laboratory precision were analyzed. The method was optimized during the collaborative validation. The results of method validation meet the requirements of the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Aiming to resolve the problems found in the collaborative validation, the medium for cell seeding, the pre-diluted buffer solution of standard and sample, and the means of removing and discarding supernatant after stimulation were optimized. After optimization, there was no significant difference in the bioactivity among the different laboratories (P > 0.05), indicating statistical equivalency. Intra-laboratory and inter-laboratory precision were good and the geometric coefficient of variation (GCV%) were both less than 15%. In conclusion, the reporter gene assay has good intra-laboratory repeatability and inter-laboratory reproducibility and is suitable for analyzing recombinant human follicle-stimulating hormone drug product and drug substance by different manufacturers. It is expected to be used as a standardized method for the determination of the in-vitro bioactivity of such products.

Survey on the application of external cardiopulmonary resuscitation in Chinese children with sudden cardiac arrest / 中华儿科杂志

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.

Comparison of diagnostic criteria for acute kidney injury in critically ill children / 中华儿科杂志

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.