AIM: To explore the clinical therapeutic effect of teprotumumab combined with glucocorticoid pulse therapy for thyroid-associated ophthalmopathy(TAO), and its impacts on thyroid function, levels of inflammatory factors, and adverse reactions in patients. METHODS: Active TAO patients admitted to the Ophthalmology Department were enrolled and randomly divide into the steroid group and the combined group. Then the steroid group was treated with glucocorticoid pulse therapy, while the combined group was combined with intravenous infusion of teprotumumab on the basis of the steroid group. The clinical therapeutic effect, the CAS, OSDI, M-C-TAO-QOL scores, ocular sign indicators(fissure width, proptosis), levels of inflammatory factors(TNF-α, CRP, IL-17), thyroid function(TSH, FT3, FT4)before and after treatment, and occurrence of adverse reactions were compared between two groups.RESULTS:Totally 96 TAO patients(192 eyes)were included, with 48 cases(96 eyes)in each group. In the combined group, there were 17 males and 31 females, with an average age of 51.85±3.53 y; in the steroid group, there were 14 males and 34 females, with an average age of 51.26±3.84 y. The total effective rate of the combined group(94%)was higher than that of the steroid group(79%)(P<0.05). After treatment, the CAS score, OSDI score, fissure width, proptosis, levels of TNF-α, CRP, and IL-17 in the combined group were all lower than those in the steroid group, and the M-C-TAO-QOL score was higher than that in the steroid group(P<0.05). However, there was no difference in thyroid function indicators and adverse reactions between two groups after treatment(P>0.05). CONCLUSION: The combination of teprotumumab and glucocorticoid pulse therapy for TAO has a prominent therapeutic effect. Meantime, it can more effectively control ocular inflammation, improve ocular signs and quality of life of patients, and has no obvious adverse effect on thyroid function, with controllable safety.

ObjectiveTo investigate the clinical effects and safety of Shuhe Granules （舒和颗粒） in patients with rheumatoid arthritis （RA） comorbid with insomnia. MethodsA single-arm prospective exploratory design was adopted. Thirty RA patients comorbid with insomnia and diagnosed with the traditional Chinese medicine （TCM） syndrome of kidney-heart deficiency and qi-blood disharmony were enrolled. On the basis of maintaining their original RA treatment regimens， all patients received oral Shuhe Granules， one dose per day， for 12 consecutive weeks. The outcomes were assessed before treatment and at weeks 4， 8， and 12 after treatment. Sleep and related psychosomatic function were evaluated using the insomnia severity index （ISI）， Pittsburgh sleep quality index （PSQI）， fatigue severity scale （FSS）， patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， and Montreal cognitive assessment （MoCA） scores. RA-related assessments included the 28-joint disease activity score based on C-reactive protein （DAS28-CRP）， pain visual analog scale （VAS）， tender joint count （TJC28）， swollen joint count （SJC28）， morning stiffness duration， and health assessment questionnaire （HAQ） score. Laboratory parameters included erythrocyte sedimentation rate （ESR）， serum C-reactive protein （CRP）， anti-cyclic citrullinated peptide antibody （anti-CCP）， and rheumatoid factor （RF） levels. A literature-based historical control group was established through literature retrieval and meta-analysis. The ISI， PSQI， DAS28-CRP， and pain VAS scores were compared between the treatment group in the present study and the historical control group. Safety assessments were also performed. ResultsCompared with baseline before treatment， ISI and PSQI scores decreased at weeks 4， 8， and 12， while MoCA scores increased at weeks 4， 8， and 12. FSS scores decreased at weeks 4 and 12. At weeks 8 and 12， GAD-7 scores， DAS28-CRP scores， duration of morning stiffness， TJC28， and SJC28 were reduced. At week 12， PHQ-9， pain VAS， and HAQ scores significantly decreased （P＜0.05）. FSS and DAS28-CRP scores at week 12 were lower than those at week 4， and CRP levels at week 8 were lower than those at week 4 （P＜0.05）. Compared with the historical control group， the treatment group showed superior improvement in ISI and PSQI scores （P＜0.001）； however， no statistically significant differences were observed between the two groups in DAS28-CRP or pain VAS scores （P＞0.05）. No serious adverse events occurred during the study， and the 4 reported mild adverse events were all considered unrelated to the study medication. ConclusionShuhe Granules significantly improve sleep quality， fatigue， emotional status， cognitive function， RA-related symptoms， and joint function in patients with RA comorbid insomnia， with good safety and tolerability.

OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg^-1）， medium-dose group （4.86 g·kg^-1）， high-dose group （9.72 g·kg^-1）， and benazepril group （0.01 g·kg^-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.

Objective To conduct a visual analysis of research hotspots and development trends in stress ulcer(SU)from 2004 to 2024 using CiteSpace software.Methods Relevant SU literature published between January 1,2004,and May 7,2024,was retrieved from the Web of Science data-base and analyzed visually using CiteSpace software.Results A total of 623 articles were included in this study.The number of publications followed a wavy increase trend from 2004 to 2024.The au-thor with the highest number of publications was MOLLER M H,the institution with the most publica-tions was Copenhagen University Hospital in Denmark,and the country with the most publications was China.Keyword analysis revealed that SU research primarily focused on exploring pathogenesis and developing prophylactic and therapeutic drugs.Conclusion The pathogenesis of SU needs further elucidation.Research on drugs and prevention tailored to different mechanisms inducing SU,the im-pact of enteral nutrition on patient prognosis,and the effectiveness of traditional Chinese medicine in prevention and treatment are hotspots and development trends in future research.

Objective To investigate the mediating role of anxiety and depression in social sup-port and burnout among primary caregivers of stroke patients.Methods A convenience sampling method was employed to select 506 primary caregivers of stroke patients as research subjects.The Gen-eral Information Questionnaire,Caregiver Burnout Inventory for Stroke Patients,Multidimensional Scale of Perceived Social Support,and Hospital Anxiety and Depression Scale were used for data col-lection.Results The total scores for caregiver burnout,social support,anxiety,and depression a-mong primarycaregivers of stroke patients were(72.83±14.32),(47.79±7.74),(10.49±3.00),and(10.45±3.06),respectively.Correlation analysis revealed a negative correlation between caregiver burnout and social support(r=-0.245,P＜0.001),and positive correlations with anxiety and depression(r=0.178,0.216,P＜0.001).Anxiety and depression partially media-ted the relationship between social support and caregiver burnout,accounting for 7.9％and 10.7％of the total effect,respectively.Conclusion Social support,anxiety,depression,and burnout are closely interrelated.Social support can directly or indirectly influence the occurrence of burnoutthrough anxiety and depression.Medical staff should pay attention to the anxiety and depression status of primary caregivers of stroke patients and enhance social support levels to reduce the incidence of burnout by alleviating anxiety and depression.

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

Objective To investigate the relationship between the levels of serum circular RNA protein tyrosine phosphatase 4A2(circ_PTP4A2),circular RNA precocious dissociation of sisters 5 homolog B(circ_PDS5B)and the volume of cerebral infarction and the degree of neurological deficits in patients with acute is-chemic stroke(AIS).Methods Ninety patients with AIS who visited the hospital from January 2021 to De-cember 2023 were selected as the AIS group,and 90 healthy individuals who underwent physical examinations during the same period were selected as the control group.The levels of serum circ_PTP4A2 and circ_PDS5B were detected by real-time fluorescence quantitative PCR,the volume of cerebral infarction was measured by magnetic resonance diffusion tensor imaging,and the degree of neurological deficit was evaluated by the Na-tional Institutes of Health Stroke Scale(NIHSS)score.According to the volume of cerebral infarction,they were divided into large-volume group(volume of cerebral infarction≥ 20 cm3,29 cases),medium-volume group(1 cm3＜volume of cerebral infarction＜20 cm3,34 cases),and small-volume group(volume of cerebral infarction≤ 1 cm3,27 cases),and according to the NIHSS scores,patients with AIS were classified into the se-vere group(NIHSS scores≥21 points,27 cases),the moderate group(NIHSS scores 5-20 points,32 cases)and the mild group(NIHSS score≤ 4 points,31 cases).Factors contributing to the increased volume of cere-bral infarction and the increased degree of neurological deficit in patients with AIS were analyzed by ordered multi-categorical Logistic regression.Results Compared with the control group,serum circ_PTP4A2 and circ_PDS5B levels were elevated in the AIS group(P＜0.05).Serum circ_PTP4A2 and circ_PDS5B levels were sequentially increased in the small-volume group,medium-volume group,and large-volume group(P＜0.05).Serum circ_PTP4A2 and circ_PDS5B levels were sequentially increased in the mild group,moderate group,and severe group(P＜0.05).Ordered multi-categorical Logistic regression showed that high NIHSS score,high circ_PTP4A2,and high circ_PDS5B were independent risk factors for increased cerebral infarction volume in AIS patients(P＜0.05),and high cerebral infarction volume,high circ_PTP4A2,and high circ_PDS5B were independent risk factors(P＜0.05).Conclusion The elevated levels of serum circ_PTP4A2 and circ_PDS5B in AIS patients are related to the increase in cerebral infarction volume and the aggravation of neurological deficits.Early detection of serum circ_PTP4A2 and circ_PDS5B levels is helpful for risk stratification in AIS patients.

PURPOSE: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*