Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Ultrasound-guided peripheral nerve block is widely used in perioperative pain management of hip fracture patients,which not only provides better analgesia,but also reduces the use of opioids,while tradi-tional techniques such as femoral nerve block and iliofascial space block often result in motor block,which is not conducive to the early rehabilitation of patients.The newly proposed pericapsular nerve block and iliopsoas plane block of the hip can preserve motor function while providing satisfactory analgesia,further in-depth re-search has found that it has great significance in the diagnosis and treatment process of patients with hip frac-tures.This article reviews the innervation of the hip joint,the methods of operation and clinical application of ultrasound-guided pericapsular nerve block and iliopsoas plane block of the hip joint,in order to provide refer-ence for clinical practice.

Objective To investigate the acoustic characteristics of speech in Parkinson's disease(PD)pa-tients compared to healthy individuals using smartphone-recorded speech,laying the foundation for future intelligent cloud-based PD detection.Methods A total of 81 PD patients and 63 healthy controls were randomly selected to re-cord their speech using Huawei,Xiao mi,and Apple smartphones through the"Active Health"screening app from the National Key R&D Program.Using the Praat library in Python,parameters such as mean fundamental frequen-cy(Mean F0),minimum fundamental frequency(Min F0),maximum fundamental frequency(Max F0),formants(F1,F2,F3,F4),shimmer,noise-to-harmonics ratio(NHR),and jitter were extracted and compared.Results In PD patients,jitter and shimmer were significantly higher in the/ba/,/bi/,/bu/,and/bo/vowels compared to the control group,while Mean F0 and Max F0 was significantly lower in/bi/and/bo/.Min F0 was significantly higher in/bi/and/bu/for PD patients.No significant differences were found in F1,F2,F3,or F4 between PD pa-tients and controls in/ba/,/bi/,/bo/and/bu/.Conclusion Quantitative analysis of smartphone-recorded speech can detect speech changes in PD patients,providing a solid foundation for the development of a cloud-based PD de-tection system.

Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043～13.057),elevated CA125 levels(OR=4.104,95%CI:1.160～14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410～11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65～0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.

Objective To investigate the acoustic characteristics of speech in Parkinson's disease(PD)pa-tients compared to healthy individuals using smartphone-recorded speech,laying the foundation for future intelligent cloud-based PD detection.Methods A total of 81 PD patients and 63 healthy controls were randomly selected to re-cord their speech using Huawei,Xiao mi,and Apple smartphones through the"Active Health"screening app from the National Key R&D Program.Using the Praat library in Python,parameters such as mean fundamental frequen-cy(Mean F0),minimum fundamental frequency(Min F0),maximum fundamental frequency(Max F0),formants(F1,F2,F3,F4),shimmer,noise-to-harmonics ratio(NHR),and jitter were extracted and compared.Results In PD patients,jitter and shimmer were significantly higher in the/ba/,/bi/,/bu/,and/bo/vowels compared to the control group,while Mean F0 and Max F0 was significantly lower in/bi/and/bo/.Min F0 was significantly higher in/bi/and/bu/for PD patients.No significant differences were found in F1,F2,F3,or F4 between PD pa-tients and controls in/ba/,/bi/,/bo/and/bu/.Conclusion Quantitative analysis of smartphone-recorded speech can detect speech changes in PD patients,providing a solid foundation for the development of a cloud-based PD de-tection system.

Objective:To investigate the relationship between thyroid autoimmunity and pregnancy outcome in patients with unexplained recurrent abortion.Methods:A retrospective cohort study of 354 patients with normal thyroid function with recurrent abortion of unknown cause admitted to Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2015 to June 2022 was used to detect thyroid antibody and thyroid function levels during pregnancy or early pregnancy. They were divided into TAI group ( n=144) and non-TAI group ( n=210) according to whether thyroid autoimmunity (TAI) was complicated or not. Tracking pregnancy outcomes. Results:Compared with the non-TAI group, the TAI group had a higher proportion of pregnancy outcomes resulting in miscarriage [42.4%(61/144) vs 27.1%(57/210), P=0.004]. In patients with unexplained recurrent abortion, TAI significantly increased the risk of spontaneous abortion [ OR(95% CI): 2.13(1.34, 3.41), P=0.001]. Positive TPOAb or TgAb also increased the risk of spontaneous abortion [ OR(95% CI): 2.18(1.37, 3.50), P=0.001; OR(95% CI): 2.33(1.31, 4.13), P=0.004]. TAI, TPOAb and TgAb had no significant interaction with age ( P=0.482, 0.724, 0.740). Conclusions:TAI is positively associated with the risk of spontaneous abortion in patients with unexplained recurrent abortion. TAI may be a potential risk factor for unexplained recurrent abortion, expanding the diagnosis and treatment of unexplained recurrent abortion.

Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME.

Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on the inflamma-tory response of lipopolysaccharide(LPS)induced acute lung injury(ALI)in mice.Methods 32 SPF KM mice,aged 4 weeks were randomly divided into four groups,control group,LPS group,dexamethasone treatment group(LPS+DEX)and BMSCs treatment group(LPS+BMSCs).The latter three groups were injected with LPS by tra-cheal puncture to establish mouse ALI model 24 h after modeling,BMSCs isolated from the femur of mice were in-jected into the caudal vein,and DEX were injected into caudal vein at the same time in LPS+DEX group for 3 consecutive days.On the 4th day after cell transplantation or 24 h after DEX injection,the survival quantity of mice was recorded,lung function was detected,and the wet/dry weight ratio(W/D)of lung was measured.Then in-flammatory cells in bronchoalveolar lavage fluid(BALF),lung pathological changes and serum inflammatory cyto-kines were collected.Green fluorescent protein(GFP)staining was used to observe the homing of BMSCs in lung tissues.The mRNA and protein expression of TLR4,MyD88 and NF-κB in lung tissues were detected by RT-PCR and Western blot assay respectively.Results Compared with the control group,LPS model group showed de-creased lung function,significantly increase in the W/D weight ratio of lung,inflammatory cytokines in serum and inflammatory cells in BALF,and severe damage in lung tissue.Compared with LPS group,LPS+DEX group and LPS+BMSCs group showed improved lung function,reduced lung tissue damage,significantly decrease in the W/D weight ratio of lung,inflammatory cytokines in serum and inflammatory cells in BALF.And the expression of TLR4-MyD88-NF-κB signaling pathway-related genes and proteins decreased,the survival quantity increased.Conclusion Homologous BMSCs transplantation can effectively treat LPS-induced acute lung injury,and the mechanism may be related to the regulation of TLR4-MyD88-NF-κB signaling pathway and the reduction of inflam-matory response.These findings provide the experimental basis for BMSCs homologous transplantation for ALI.

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.

The incidence rate of chronic hepatitis B remains high in China. Antiviral therapy can significantly reduce the risk of progressive liver disease and hepatocellular carcinoma in patients with chronic hepatitis B. However, all current antiviral treatments can only inhibit HBV replication and not completely eliminate the hepatitis B virus, so antiviral therapy for chronic hepatitis B is probably a long-term or even lifelong treatment. Antiviral therapy compliance is essential for achieving long-term clinical benefits and preventing nucleot(s)ide drugs resistance. Herein, we analyzed the relevant factors of antiviral therapy compliance and their impact on CHB treatment and explored feasible programs that can improve compliance with nucleot(s)ide drug treatment by conducting a literature search using PubMed and Scopus with search terms including hepatitis B, compliance, nucleot(s)ide drugs, antiviral therapy, viral suppression, and drug resistance.