Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective To investigate the effect of the use of glycopyrrolate before anesthesia on the perioperative circulation of patients undergoing laparoscopic cholecystectomy(LC).Methods 88 patients undergoing LC from March to June in 2024 were enrolled and randomly divided into two groups:the glycopyrrolate group(group G)and the control group(group C),with 44 patients in each.Three patients from group G and four from group C were excluded,leaving 41 patients in group G and 40 patients in group C.Ten minutes before anesthesia induction,group G received an intravenous dose of 4 μg/kg glycopyrrolate diluted to 5 mL with normal saline.The control group received an equal volume of normal saline.Both groups then received an intravenous infusion of dexmedetomidine at 1 μg/kg over 10 minutes.Heart rate(HR)and mean arterial pressure(MAP)were monitored immediately before infusion of glycopyrrolate/saline(T0),5 min after infusion(T1),10 min after infusion(T2),1 min after tracheal intubation(T3),immediately at skin incision(T4),2 min after pneumoperitoneum(T5),dissociating the cholecyst(T6),and 1 min after tracheal tube drawing(T7).Intraoperative amounts of propofol,rocuronium bromide,sufentanil,remifentanil,oral secretion score,PACU stay time,first postoperative flatus time and the occurrence of perioperative adverse reactions were observed.Results HR at T2,T3,T4,T5,and T6 time points was significantly higher in group G than in group C,while MAP at T1,T2,T3,T4,T5 time points was also significantly higher in group G(P<0.05).HR at T2 time points in Group G was significantly lower than that at T0,while T7 was significantly higher than that at T0 time points.In Group C,HR at T1,T2,T4,T5,and T6 time points was significantly lower than that at T0 time points,while T7 time points was significantly higher than that at T0 time points,with the differences being statistically significant(P<0.05).In Group G,MAP at T1 and T2 time pointswas significantly higher than that at T0,and MAP at T6 was significantly lower than that at T0 time points,and in Group C,MAP at T4,T5 and T6 time points was significantly lower than that at T0 time points,and the differences were all statistically significant(P<0.05);Oral secretion was lower in group G compared to group C,with a significant difference(P<0.05).The incidence of bradycardia was significantly lower in group G compared to group C(P<0.05).The incidence of oral dryness within 24 h postoperatively was higher in group G compared to group C(P<0.05).There were no significant differences of HR at T0,T1,and T7 time points,MAP at T0,T6,and T7 time points between the two groups(P>0.05);There were no significant differences of operation time,propofol usage,sufentanil usage,remifentanil usage,rocuronium bromide usage during operation,rate of atropine use,incidence of intraoperative hypotension,PACU stay time,first postoperative flatus,and nausea vomiting rate between the two groups(P>0.05);No delirium occurred in either group of patients 24 h after the operation.Conclusion Use of glycopyrrolate before anesthesia can be effectively applied to patients undergoing LC,is beneficial in reducing the incidence of bradycardia,maintaining the stability of intraoperative circulation,and has no significant effect on the incidence of postoperative delirium and nausea and vomiting.It is a worthy clinical application.

Puerarin is a monomeric isoflavone compound derived from Puerariae Lobatae Radix. It exhibits poor solubility in both water and lipids, resulting in suboptimal oral absorption and low bioavailability. There is therefore an urgent need to develop new methods of applying puerarin to enhance its solubility and bioavailability. Studies have revealed that puerarin possesses distinctive physical and chemical properties, including the ability to self-assemble into supramolecular hydrogels in response to temperature changes. In this review, the research progress of puerarin as a hydrogel system containing loaded drugs, as well as a hydrogel system composed of hydrogel matrix in the field of tissue regeneration was summarized. This is intended to provide a reference for the rational and efficient use of drugs and lay the groundwork for the development and preparation of new drug carrier platforms.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

The CDH23 gene is a pathogenic mutant gene of the USH1D subtype in Usher syndrome.In this study,two wild-type Cdh23 full-length plasmids(～16 kb)with different promoters were construc-ted,and fluorinated polyethylene imine(FPEI)was used as a delivery vector to transfect the house ear institute-organ of corti 1(HEI-OC1)and the optimal expression plasmid was obtained by evaluating the transfection efficiency in vitro.Firstly,the results of the synthesis of FPEI were analyzed using Fourier transform infrared absorption spectroscopy to prove the successful synthesis of FPEI.After that,the plas-mid encapsulation ability of FPEI and the surface potential and hydration diameter of the formed comple-xes were characterized by agarose gel blocking assay,Zeta potential assay,and dynamic light scattering assay.It was found that FPEI had good plasmid encapsulation ability,and the FPEI plasmid complexes were all positively charged at high mass ratio,with the distribution of particle sizes in the range of 100-300 nm.The low cytotoxicity and high transfection efficiency of FPEI in HEI-OC1 cells were verified by Cell Counting Kit-8(CCK-8)and flow cytometry.Comparing FPEI with Lipofectamine 3000 and differ-ent quality PEI(25K,40K)transfection reagents,the transfection efficiency of FPEI was found to be significantly better than that of the traditional transfection reagents.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot results showed that the CAG promoter was better than the CMV promoter,which could be used as the optimal expression plasmid for the subsequent in vivo experi-ments.In addition,it was verified by cellular immunofluorescence that CDH23 was mainly distributed in the cytoplasm after overexpression.The above results demonstrated that FPEI can be used as an efficient delivery vector for in vitro overexpression of large genes represented by Cdh23,which provides an impor-tant experimental basis for subsequent in vivo gene therapy of USH1D syndrome.

Objective To investigate the effect of the use of glycopyrrolate before anesthesia on the perioperative circulation of patients undergoing laparoscopic cholecystectomy(LC).Methods 88 patients undergoing LC from March to June in 2024 were enrolled and randomly divided into two groups:the glycopyrrolate group(group G)and the control group(group C),with 44 patients in each.Three patients from group G and four from group C were excluded,leaving 41 patients in group G and 40 patients in group C.Ten minutes before anesthesia induction,group G received an intravenous dose of 4 μg/kg glycopyrrolate diluted to 5 mL with normal saline.The control group received an equal volume of normal saline.Both groups then received an intravenous infusion of dexmedetomidine at 1 μg/kg over 10 minutes.Heart rate(HR)and mean arterial pressure(MAP)were monitored immediately before infusion of glycopyrrolate/saline(T0),5 min after infusion(T1),10 min after infusion(T2),1 min after tracheal intubation(T3),immediately at skin incision(T4),2 min after pneumoperitoneum(T5),dissociating the cholecyst(T6),and 1 min after tracheal tube drawing(T7).Intraoperative amounts of propofol,rocuronium bromide,sufentanil,remifentanil,oral secretion score,PACU stay time,first postoperative flatus time and the occurrence of perioperative adverse reactions were observed.Results HR at T2,T3,T4,T5,and T6 time points was significantly higher in group G than in group C,while MAP at T1,T2,T3,T4,T5 time points was also significantly higher in group G(P<0.05).HR at T2 time points in Group G was significantly lower than that at T0,while T7 was significantly higher than that at T0 time points.In Group C,HR at T1,T2,T4,T5,and T6 time points was significantly lower than that at T0 time points,while T7 time points was significantly higher than that at T0 time points,with the differences being statistically significant(P<0.05).In Group G,MAP at T1 and T2 time pointswas significantly higher than that at T0,and MAP at T6 was significantly lower than that at T0 time points,and in Group C,MAP at T4,T5 and T6 time points was significantly lower than that at T0 time points,and the differences were all statistically significant(P<0.05);Oral secretion was lower in group G compared to group C,with a significant difference(P<0.05).The incidence of bradycardia was significantly lower in group G compared to group C(P<0.05).The incidence of oral dryness within 24 h postoperatively was higher in group G compared to group C(P<0.05).There were no significant differences of HR at T0,T1,and T7 time points,MAP at T0,T6,and T7 time points between the two groups(P>0.05);There were no significant differences of operation time,propofol usage,sufentanil usage,remifentanil usage,rocuronium bromide usage during operation,rate of atropine use,incidence of intraoperative hypotension,PACU stay time,first postoperative flatus,and nausea vomiting rate between the two groups(P>0.05);No delirium occurred in either group of patients 24 h after the operation.Conclusion Use of glycopyrrolate before anesthesia can be effectively applied to patients undergoing LC,is beneficial in reducing the incidence of bradycardia,maintaining the stability of intraoperative circulation,and has no significant effect on the incidence of postoperative delirium and nausea and vomiting.It is a worthy clinical application.