Currently,breast cancer is a common malignancy in female,and previous guidelines recommended that one of the key biomarkers for breast cancer,human epidermal growth factor receptor 2(HER2),is classified as either positive or negative to guide clinicians'treatment decisions.While nearly half of breast cancer patients have low HER2 expression(IHC expression is 1+or 2+and ISH detection is negative),such patients are insensitive to traditional anti-HER2 targeted therapy.However,novel antibody-drug conjugates(ADCs)provide new targeted therapy options for breast cancer patients with low HER2 expression,challenging the traditional binary concept and arousing research enthusiasm.In the latest ASCO/CAP guidelines for HER2 detection in breast cancer,HER2-low breast cancer has been included as a clinical treatment subgroup.This article will review the definition of HER2-low breast cancer,the progress of drug therapy such as ADC,and the current challenges faced by this subgroup.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

Background::Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods::Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.Results::Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%-3.10%), 2.09% (95% CI: 1.76%-2.43%), and 1.25% (95% CI: 0.99%-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions::Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Objective To explore the application value of modified prophylactic ileostomy in natural orifice specimen extraction surgery(NOSES)for patients with mid-low rectal cancer.Methods We retrospectively analyzed 63 patients who received prophylactic ileostomy in NOSES for mid-low rectal cancer in our hospital from September 2017 to May 2023.The patients were divided into the observation group(those who received modified ileostomy,n=31)and the control group(those who received conventional loop ileostomy,n=32)according to different ostomy methods.The operation time of ostomy,operation time of ostomy reversal surgery,early-stage complications(stoma leakage,peristomal dermatitis,stoma pain,peristomal trocar hole infection,stoma bleeding,stoma ischaemic necrosis,stoma oedema,peristoma skin-mucosal separation and stoma proximal bowel obstruction)and long-stage complications(stoma stenosis,stoma retraction,stoma prolapse,parastomal hernia),tumor recurrence and death of the two groups were compared and analyzed.Results Both prophylactic ileostomy and ostomy reversal surgery were successfully completed in all the 63 cases.The operation time of ostomy in the observation group was 7(6-8)min,which was significantly shorter than that of 23(21-24)min in the control group(Z=-6.853,P=0.000),and the operation time of ostomy reversal surgery in the observation group was(63.2±5.7)min,which was significantly shorter than(93.5±4.7)min in the control group(t=-23.109,P=0.000).Neither stoma bleeding nor stoma ischaemic necrosis were observed in both groups.The incidence of stoma pain in the observation group was lower than that in the control group[6.4％(2/31)vs.65.6％(21/32),x2=21.766,P=0.000].The incidence of peristomal incision infection in the observation group was lower than that in the control group[0％(0/31)vs.53.1％(17/32),P=0.000].There was no stoma stenosis in both groups.There were 3 cases of parastomal hernia,1 case in the observation group and 2 cases in the control group,the difference of the incidence being not statistically significant(P=1.000).There was 1 case of stoma retraction and 1 case of stoma prolapse in the control group.All the 5 cases with complications received prompt treatment in the second ostomy reversal surgery.Follow-up visits for 6-60 months in the 63 cases showed no tumor recurrence or death.Conclusion Modified prophylactic ileostomy in NOSES for patients with mid-low rectal cancer is safe,feasible,and easy to operate,having certain practicality and promotion value.

This article reports a case of prenatal diagnosis of fetal Costello syndrome. At 11 weeks of gestation, the fetal nuchal translucency thickness was 2.5 mm. At 26 +1 weeks of gestation, ultrasound indicated that the fetal abdominal circumference was significantly enlarged, suggesting fetal overgrowth. Subsequent regular ultrasound follow-ups revealed polyhydramnios, enlarged fetal kidneys, and macroglossia after 30 +5 weeks of gestation. Whole-exome sequencing of the family detected a c.34G>A(p.Gly12Ser) mutation in the fetal HRAS gene, which was pathogenic and not present in either parent. Based on clinical manifestations, the fetus was diagnosed with Costello syndrome. After genetic counseling, the pregnant woman opted for termination of the pregnancy.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metab-olomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of devel-oping SMDCs for precise cancer therapy.

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Objective:To explore the risk factors affecting the incidence of acute kidney injury(AKI)after liver transplantation(LT).Methods:From November 2019 to November 2022, clinical data were retrospectively reviewed for 105 recipients of classic orthotopic LT.There are 89 males and 16 females with an age range of(50.52±10.35)years.They are assigned into two groups of AKI(66 cases)and non-AKI(39 cases)according to the AKI diagnostic and staging criteria of Global Kidney Disease Prognosis Organization in 2012.General profiles and clinical data(e.g.previous medical history, MELD score, total bilirubin, albumin, serum creatinine level, coagulation function, anhepatic phase and time to surgery)of two groups of recipients are compared.The factors with statistically significant differences are included into multivariate Logistic regression analysis for obtaining independent risk factors for early AKI post-LT.Results:Among them, 66 patients developed AKI within 7 days post-operation with an incidence rate of 62.86%(66/105).The clinical stages of AKI are Ⅰ(46 cases, 69.70%), Ⅱ(10 cases, 15.15%)and Ⅲ(10 cases, 15.15%).Statistically significant inter-group differences exists in age, abdominal surgery history, preoperative serum level of creatinine, operative duration, anhepatic phase and intraoperative plasma transfusion(all P<0.05).Multivariate Logistic regression analysis indicated that abdominal surgery history( OR=5.803, 95% CI: 1.008~33.401, P=0.049), anhepatic phase( OR=1.054, 95% CI: 1.008~1.101, P=0.020)and preoperative serum level of creatinine( OR=0.968, 95% CI: 0.943~0.994, P=0.016)are independent risk factors for early AKI after classical orthotopic LT recipients. Conclusions:Abdominal surgery history, anhepatic phase, and preoperative serum level of creatinine are independent risk factors for early AKI in classic orthotopic LT recipients.