Elderly patients with lung cancer have a significantly increased risk of perioperative cardiopulmonary complications due to physiological decline, high incidence of complications and reduced surgical tolerance, which directly affects postoperative recovery and long-term survival. Although the concepts of minimally invasive surgery and enhanced recovery after surgery have improved clinical outcomes, early recognition and intervention of postoperative complications in elderly patients remains a significant challenge in the field of thoracic surgery. By integrating recent literature and clinical practice, this paper systematically analyzes the pathophysiological mechanism and risk factors of perioperative cardiopulmonary complications in elderly patients with lung cancer, and discusses individualized intervention strategies based on risk stratification and multidisciplinary team, in order to provide theoretical basis and practical guidance for optimizing perioperative management and improving postoperative prognosis in elderly patients.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

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.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective:To assess the real-world triage performance of a dual-marker strategy (DMS) combining copeptin and high-sensitivity cardiac troponin T (hs-cTnT) in patients presenting with chest pain and suspected non-ST-segment elevation myocardial infarction (NSTEMI).Methods:It was conducted a prospective study of 277 consecutive chest pain patients admitted to the Emergency Department of Zhongshan Hospital, Fudan University, between July and August 2023. Admission levels of copeptin and hs-cTnT were measured. The safety, efficacy, and triage efficiency of the DMS (defined as copeptin <10 pmol/L and hs-cTnT <0.014 ng/mL) for excluding NSTEMI were evaluated based on final diagnoses and clinical outcomes.Results:Among 277 patients, 141 (50.9%) had cardiogenic diseases (51 NSTEMI, 37 unstable angina pectoris [UAP], 11 myocardial bridges, and 42 non-coronary artery disease), 29 (10.5%) had non-cardiac conditions, and 107 (38.6%) had low-risk chest pain of unknown etiology. A total of 103 patients (37.2%) were DMS-negative (copeptin and hs-cTnT both below cutoff), including 0 NSTEMI cases, 2 UAP cases, 1 myocardial bridge, 6 non-coronary artery diseases, 4 non-cardiac conditions, and 90 low-risk cases. The DMS demonstrated a negative predictive value (NPV) of 100% for excluding NSTEMI, with no major adverse cardiac events (MACE) observed in DMS-negative patients during 30-day follow-up. Real-world data revealed that only 42.2% of suspected NSTEMI patients received a second troponin test (timing: 1 hour—5.9%, 2 hours—23.9%, ≥3 hours—70.1%). The DMS enabled safe and efficient triage of 37.2% of chest pain patients at 0-hour, outperforming other strategies in applicability and feasibility ( P < 0.05). Conclusions:In real-world clinical practice, the DMS (copeptin combined with hs-cTnT) optimally complements guideline-recommended hs-cTnT algorithms. It provides a simple, rapid, and safe approach to managing acute chest pain, demonstrating superior applicability for improving emergency triage efficiency.

Objective:To evaluate the radiological and functional outcomes of moderate to severe hallux valgus patients with enlarged distal metatarsal articular angle (DMAA) underwent modified Chevron osteotomy.Methods:The clinical data of patients with moderate and severe hallux valgus with increased distal metatarsal joint angle who accepted surgery operation in the Department of Foot and Ankle Surgery of Yantaishan Hospital from October 2020 to December 2022 were retrospectively analyzed. All patients underwent modified Chevron osteotomy. Taking the proximal end of the metatarsal head centre as the osteotomy apex, the vertical arm osteotomy line in the sagittal plane made an angle of ≤80° with the metatarsal stem, the horizontal plane was inclined to the lateral distal end of the metatarsal head by about 10°, and the sagittal plane metatarsal arm osteotomy line made an angle of ≥90° with the vertical arm osteotomy line; at the proximal osteotomy surface, another cuneiform bone with its base on the medial and its apex on the lateral was resected. The deformity correction was insufficient and Akin osteotomy was performed in combination. Weil osteotomy was performed in combination with metatarsalgia. Radiological assessment including the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, the joint congruity angle (JCA), forefoot bone width and soft tissue width was performed preoperatively and at last follow-up postoperatively. American Orthopedic Foot and Ankle Society/hallux metatarsophalangeal-interphalangeal scale (AOFAS/HMIS) was used for clinical and functional evaluation, total score from 0 to 100, with higher scores indicating better function.Visual analogue scale (VAS) was used for pain valuation, total score from 0 to 10, with higher scores indicating more pain. A questionnaire survey on patient satisfaction was conducted at the last follow-up. Shapiro-Wilk test was used for normal distribution test, and measurement data following normal distribution were represented as Mean±SD. Paired t-test was used for comparison before and after operation. Other indicators conformed to non-normal distribution were denoted by M( Q1, Q3) and were tested by Wilcoxon signed-rank test. P<0.05 was considered statistically significant. Results:Fifty-two feet of 48 patients (5 males, 43 females; mean age (52.4±14.9) years; range, 24 to 78 years) were enrolled. Before the operation, 8 feet combined with metatarsalgia, among them, 7 feet underwent modified Chevron+ Akin+ Weil osteotomy, and 1 foot underwent modified Chevron+ Weil osteotomy. Among the 44 feet without metatarsalgia, 11 feet underwent modified Chevron osteotomy and 33 feet underwent modified Chevron+ Akin osteotomy. The mean follow-up time was 17.8 months (12-24 months). The HVA angle decreased from 38.30°±7.59° before surgery to 10.00°±5.73° at the last follow-up; the IMA angle decreased from 16.08°(12.89°, 18.24°) to 4.81°(3.62°, 7.57°); the DMAA angle decreased from 18.35°(13.03°, 27.47°) to 4.52°(2.68°, 7.09°); JCA decreased significantly from 15.93°(10.25°, 23.06°) to 3.56°(1.71°, 6.98°); forefoot bone width decreased from (90.05±6.12) mm to (82.75±5.01) mm; forefoot soft tissue width decrease from 102.25(96.77, 107.15) mm to 98.08(91.01, 100.60) mm; the VAS decreased from 6(5.5, 7) points to 0(0, 0) points; the score according to the AOFAS/HMIS forefoot was increased from 49(42, 52.5) points to 90(83.5, 95) points; which were statistically significant compared with that before the operation (all P<0.01). There was no statistically significant difference in the first metatarsal length before the operation and at the last follow-up [54.60(52.86, 56.42) mm vs. 54.29(51.85, 56.35) mm, P>0.05]. In the post-operative period, there were 8 feet had limited metatarsophalangeal joint movement, 3 feet had limited interphalangeal joint movement, 5 feet had limited movement in both joints, which did not affect walking and function; 3 feet of partial recurrence of hallux valgus, 2 feet of screw irritation pain, 1 foot of cystic degeneration of the first metatarsal head, and no complications such as metastatic metatarsalgia. The satisfaction survey showed that the satisfaction rate of patients with the orthopedic effect was 90.4% (47/52). Conclusion:The modified Chevron osteotomy is effective in the treatment of moderate to severe hallux valgus with enlarged DMAA. Careful intraoperative operation and standardized postoperative rehabilitation training can reduce complications.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.