INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

The study is designed to observe the mechanism of Tongfu Xiefei Guanchang Solution(TFXF) in the treatment of acute lung injury(ALI) in rats by improving intestinal barrier and intestinal flora structure via p38 mitogen-activated protein kinase(p38 MAPK)/myosin light chain kinase(MLCK) signaling pathway. Sixty SPF-grade Wistar rats were randomly divided into the control(CON) group, lipopolysaccharide(LPS) group(7.5 mg·kg~(-1)), LPS + dexamethasone(DEX) group(3.5 mg·kg~(-1)), LPS + high-dose(HD)-TFXF group(14.74 g·kg~(-1)), LPS + middle-dose(MD)-TFXF group(7.37 g·kg~(-1)), and LPS + low-dose(LD)-TFXF group(3.69 g·kg~(-1)). ALI model of the rat was established by intraperitoneal injection of LPS. The lactate dehydrogenase(LDH) activity and total protein concentration in the bronchoalveolar lavage fluid(BALF) were measured; tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) levels in lung and colon tissue of rats were detected by enzyme linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the pathological expression in the lung and colon tissue of rats. The mRNA expression of p38 MAPK, TNF-α, and IL-1β in rat lung tissue was determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). Western blot was used to detect the protein expression related to the p38 MAPK/MLCK signaling pathway in the colon tissue of rats. 16S rRNA sequencing was used to detect changes in the composition and content of intestinal flora in rats, and correlation analyses were performed to explore the regulatory role of intestinal flora in improving ALI in rats. The results showed that compared with those in the LPS group, the histopathological scores of lung and colon tissue, LDH activity, and total protein concentration in BALF were significantly reduced in rats in all groups after drug administration. Except for the LPS + LD-TFXF group, the remaining groups significantly reduced the levels of TNF-α and IL-1β in the lung and colon tissue of rats. The protein expressions of phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)/p38, phosphorylated myosin light chain(p-MLC)/myosin light chain 2(MLC2), and MLCK in colon tissue of rats in each drug administration group were significantly decreased. The mRNA expression levels of p38 MAPK, TNF-α, and IL-1β were significantly reduced in the LPS + HD-TFXF group. 16S rRNA sequencing results showed that the abundance of intestinal flora was significantly higher in the LPS + HD-TFXF group, and intestinal floras including Sobs, Shannon, and Npshannon were significantly higher. The β-diversity distribution of intestinal flora tends toward the CON group, and the abundance of Firmicutes was significantly higher. The abundance of Proteobacteria was significantly reduced; the abundance of Bacteroides was significantly reduced, and the abundance of Ruminococcus was significantly higher. The main species differences were Blautia, Roseburia＿sp＿499, and Butyricicoccus. TNF-α and IL-1β of lung tissue were negatively correlated with Muribaculaceae, unclassified norank＿f＿Eubacterium＿coprostanoligenes, and Ruminococcus and positively correlated with Bacteroides. Meanwhile, TNF-α and IL-1β of colon tissue were negatively correlated with unclassified norank＿f＿Eubacterium＿coprostanoligenes and Ruminococcus and positively correlated with Bacteroides. The predicted biological function of the flora was related to the biosynthesis of secondary metabolites, amino acid biosynthesis, sugar metabolism, and oxidative phosphorylation. The above studies show that TFXF can repair lung and colon tissue structure and regulate inflammatory factor levels by modulating the abundance and diversity of intestinal flora species in ALI rats. Its mechanism of action in ameliorating ALI in rats may be related to the inhibition of inflammation, improvement of intestinal mucosal permeability, and maintenance of intestinal flora homeostasis and barrier through the p38 MAPK/MLCK signaling pathway.
Animals ; Acute Lung Injury/genetics* ; Rats ; p38 Mitogen-Activated Protein Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Myosin-Light-Chain Kinase/genetics* ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Wistar ; Signal Transduction/drug effects* ; Interleukin-1beta/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung/metabolism* ; Intestinal Mucosa/metabolism* ; Humans

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L₄ to L₆, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L₄ to L₆ , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Animals ; Female ; Male ; Rabbits ; Electroacupuncture ; Muscle, Skeletal ; Muscular Atrophy/therapy* ; NF-kappa B/genetics* ; Peripheral Nerve Injuries ; Rats, Sprague-Dawley ; Sciatic Nerve