Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.

Nonsteroidal anti-inflammatory drugs(NSAIDs)are widely used to treat osteoarthritis,rheumatoid arthritis,and acute and chronic painful diseases.Significant interindividual heterogeneity in the efficacy of NSAIDs has been found in patients,which can lead to treatment failure or life-threatening adverse drug reactions.This review will discuss the causes of the variability in the efficacy of NSAIDs in terms of CYP2C9 enzyme gene polymorphism,cyclooxygenase enzyme gene polymorphism,and differences in the intestinal microbiota,to provide a reference for the development of individualized dosing regimens for NSAIDs.

The lack of preoperative guidelines for the management of drugs for psychiatric disorders will affect the quality of surgical management of psychiatric patients and increase the probability of perioperative complications.To standardize the preoperative management of medications for the treatment of mental disorders,the Perioperative Assessment and Quality Improvement Society issued《Preoperative Management of Medications for Psychiatric Diseases:Society for Perioperative Assessment and Quality Improvement Consensus Statement》in February 2022 to provide clinicians with recommendations for the preoperative management of psychotropic medications.This article interpreted the consensus,summarized the perioperative interactions,special precautions,and auxiliary examination precautions,and provided corresponding preoperative suggestions on antidepressants,mood stabilizers,anxiety,antipsychotics,and attention deficit hyperactivity disorder drugs,to provide a reference for the standardized management of perioperative drugs.

Uncontrolled hypertension in the perioperative period may affect the hemodynamic stability of patients during surgery and thus affect the prognosis of patients.This increases the risk of other complications and death.For hypertensive patients undergoing surgery,it is necessary to weigh the pros and cons,and choose appropriate antihypertensive drugs to reduce the incidence of perioperative adverse events.There is no unified conclusion on perioperative blood pressure management in China.This paper systematically reviewed the perioperative blood pressure control objectives and drug use programs,including non-cardiac surgery,cardiac surgery,pregnancy,and pheochromocytoma.It provided a reference for the perioperative management of hypertensive patients.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved ¹O₂ generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Chronic obstructive pulmonary disease (COPD) has a high global morbidity and mortality and a severe disease burden, yet progress in treatment and prevention has been slow in recent decades. Early COPD has few symptoms and is severely underdiagnosed and undertreated; it is crucial to search for effective clues of early COPD and provide management interventions. By reviewing the definition, risk factors, diagnosis and management interventions, this study explores the disease evolution of early-stage COPD, which can help clinical practice to develop more effective preventive and therapeutic strategies for stopping or slowing down the natural progression of the disease, improving the long-term prognosis, and reducing the disease burden.
Humans ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Prognosis ; Risk Factors

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*