ObjectiveTo predict the mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer via network pharmacology and validate the prediction results in animal experiments. MethodsThe potential mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer was predicted by network pharmacology， liquid chromatography-mass spectrometry （LC-MS）， and molecular docking methods. C57/BL6 mice were assigned into normal， model， cisplatin， and Shasheng Maidong Tang+cisplatin groups. In addition to the normal group， the remaining groups were injected subcutaneously with 0.2 mL of 1×10⁷ cells·mL^-1 Lewis lung cancer cells to establish the Lewis lung cancer model. The daily gavage dose of Shasheng Maidong Tang was 3.58 g·kg^-1， and the concentration of cisplatin intraperitoneally injected on every other day was 2 mg·kg^-1. Drugs were administered for 14 d. The changes in the tumor volume and the rate of tumor suppression were monitored， and the tumor histopathological changes were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay was employed to measure the interleukin （IL）-6 and interferon （IFN）-γ levels in peripheral blood. Real-time PCR was performed to quantify the mRNA levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription 1 （STAT1）， and signal transducer and activator of transcription 3 （STAT3） in the tumor tissue of mice. Western blot was employed to determine the protein levels of JAK2， STAT3， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， and Pim-1 proto1 （PIM1） in the tumor tissue. Immunohistochemistry was employed to detect the expression of Bcl-2 and PIM1 in the tumor tissue. ResultsNetwork pharmacological predictions indicated that Shasheng Maidong Tang might enhance the efficacy of chemotherapy for lung cancer by regulating nitrogen metabolism， AGE-RAGE signaling pathway， cancer pathway， and JAK/STAT signaling pathway. The experimental results demonstrated that tumor volume in the cisplatin group and Shasheng Maidong Tang+cisplatin group was reduced compared with the model group， with statistically distinct differences observed on days 14， 17， 20 post modeling （P<0.05）. Notably， the Shasheng Maidong Tang+cisplatin therapy further decreased tumor volume compared with the cisplatin group， showing marked reductions on days 17 and 20 （P<0.05）， consistent with trends visualized in tumor volume comparison charts. The Shasheng Maidong Tang+cisplatin group exhibited higher tumor inhibition rate than the cisplatin group （P<0.05）. Histopathological analysis via HE staining revealed that the tumors in the model group displayed frequent nuclear mitosis， densely arranged cells， hyperchromatic nuclei， and no necrosis. Cisplatin treatment induced partial necrosis and vacuolization， while the Shasheng Maidong Tang+cisplatin group exhibited extensive necrotic regions， maximal vacuolization， disarranged tumor cells， and minimal mitotic activity. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed elevated level of IFN-γ （P<0.01） and declined level of IL-6 （P<0.01） in the peripheral blood. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented elevated level of IFN-γ （P<0.01） and lowered level of IL-6 （P<0.01） in the peripheral blood. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin groups showed down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level STAT1 （P<0.01）. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level of STAT1 （P<0.01）. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， and STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. Compared with the cisplatin group， Shasheng Maidong Tang+cisplatin group presented down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. The Bcl-2 and PIM1 expression results obtained by immunohistochemistry were consistent with those of Western blot. ConclusionShasheng Maidong Tang may enhance the efficacy of chemotherapy in the mouse model of Lewis lung cancer by regulating the JAK2/STAT3 signaling pathway.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

The discovery of streptomycin in 1943 marked a new era in plague treatment. Over the subsequent eight decades, significant advances have been made through the implementation of various antibiotics, both as monotherapy and in combination regimens. These treatments have included aminoglycosides (such as streptomycin and gentamicin), tetracyclines, sulfonamides, chloramphenicol, quinolones, and beta-lactams, which have dramatically cut down the death rate from plague infections. However, due to bacterial adaptation mechanisms, Yersinia pestis can develop diminished sensitivity or resistance to certain antibiotics. This article examines the resistance mechanisms of Yersinia pestis and analyzes antimicrobial susceptibility patterns and resistance in plague treatment, aiming to provide scientific evidence for clinicians to understand the current status of traditional and new antibiotics in plague treatment and improve the treatment level of plague patients.

Objective To investigate the protective effect and mechanism of calcium dobesilate on oxidative damage induced by high-glucose in Müller cells.Methods The oxidative damage model of Müller cells induced by high-glucose was established and the cells were divided into 4groups.The control group was cultured normally,and the high glucose group was cultured in the medium of 35mmol/L glucose.The control+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of routine culture,and the high sugar+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of high glucose.Cell proliferation was assessed by CCK-8,apoptosis was detected by flow cytometry,and oxidative stress markers were detected by the kit.Intracellular correction potassium channel subtype 4.1(Kir4.1)and aquaporin 4(AQP4)protein levels were detected by western blot.Results Compared with the control group,the proliferative activity of Müller cells of the high glucose group was decreased,apoptosis rate was increased,oxidative stress occurred,AQP4 protein expression level was increased and Kir4.1 protein level was decreased(P＜0.05).Compared with the high glucose group,the cell activity and apoptosis rate of the high glucose+calcium do-besilate group were increased,the oxidative stress damage was alleviated,the AQP4 protein expression level was decreased and the Kir4.1 protein level was increased(P＜0.05).Conclusion Calcium dobesilate may inhibit the oxidative damage of Müller cells induced by high-glucose by regulating the AQP4/Kir4.1 axis.

Objective To investigate the clinical characteristics of hospitalized children with pertussis based on their pertussis vacci-nation status.Methods From March,2011 to February,2022,children with pertussis hospitalized at the Children's Hospital Affiliated to Capital Institute of Pediatrics were retrospectively selected.Information was analyzed regarding demographic data and clinical data,Pa-tients were divided into three groups based on vaccination status:non-vaccinated,incompletely vaccinated(1dose or 2doses),and com-pletely vaccinated(3doses).Clinical features were compared among the groups.Results A total of 270 children hospitalized with pertus-sis were included.The non-vaccinated group comprised 206 cases(76.3％),the incompletely vaccinated group comprised 24 cases(8.9％),and the completely vaccinated group comprised 40 cases(14.8％).Statistically significant differences were observed in the overall age of onset among the three groups(P＜0.05),with the completely vaccinated group having the highest age of onset.Significant differences were also noted in the proportions of hypoxemia,decreased heart rate,paroxysmal cough,episodic cyanosis,facial flushing during coughing,and elevated peripheral blood lymphocyte proportion(≥0.6)across the groups(P＜0.05),with the completely vacci-nated group showing lower rates compared to the non-vaccinated group.Additionally,significant differences were observed in the rates of severe pertussis and the need for mechanical ventilation(invasive or non-invasive)among the groups(P＜0.05),with the completely vaccinated group having lower rates than the non-vaccinated group.Conclusion Complete vaccination,plays a critical role in allevia-ting clinical symptoms,reducing peripheral blood lymphocytosis,and decreasing the incidence of severe pertussis in children.

Objective:To investigate the trends in insulin resistance, as represented by the triglyceride-glucose index (TyG index), among Chinese adult residents from 2010 to 2018 and to explore influencing factors.Methods:China Chronic Disease and Risk Factor Surveillance was conducted in 2010, 2013, and 2018, using a multi-stage stratified cluster random sampling method across all 31 provinces (autonomous regions and municipalities) in China. This study sampled 98 712 adults in 2010, 176 534 adults in 2013, and 184 876 adults in 2018, all aged ≥18 years, totaling 406 933 participants. Individuals with a TyG index > P75 were classified as having insulin resistance. The mean TyG index and the prevalence of insulin resistance were calculated for different years, sexes, age groups, provinces (autonomous regions and municipalities), and subgroups for 2018. Linear and logistic regression models were used to test trends in means and rates over time, and multivariate logistic regression models were conducted to analyze potential factors associated with insulin resistance. All analyses were adjusted for complex sampling weights based on the study design. Results:From 2010 to 2018, the mean TyG index among Chinese adults increased from 8.44±0.63 to 8.70±0.64, with significant upward trends observed across different age groups, sexes, and urban-rural residencies (all P<0.001). The mean TyG index was higher among males, urban residents, and those aged 45-59. There were significant differences in the mean TyG indices and prevalence of insulin resistance across provinces (autonomous regions and municipalities) (all P<0.05). Higher insulin resistance prevalence was independently associated with being male, aged ≥45 years, living in urban areas, excessive alcohol consumption, and insufficient physical activity (all P<0.05). Conclusions:From 2010 to 2018, the level of insulin resistance, as indicated by the TyG index, showed an increasing trend among Chinese adults. Males, individuals aged ≥45 years, urban residents, and individuals with unhealthy lifestyles such as excessive alcohol consumption or insufficient physical activity should be the focus of efforts to prevent and control metabolic diseases related to insulin resistance.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Objective:To present the epidemiological characteristics of ≤28 days case fatality in both hemorrhagic stroke (HS) and ischemic stroke (IS) patients in national cardiovascular disease surveillance areas from 2015 to 2019.Methods:Data on all new patients with stroke and ≤28 days outcomes from 2015 to 2019 were from the China Registry of Cardiovascular Events, which was established in 2014, covering 100 counties (cities, districts) in 31 provinces in China. Poisson regression was used to analyze the annual trend of ≤28 days case fatality. The age-standardized case fatality was directly calculated based on all new stroke onset.Results:In total, 112 069 deaths in HS patients ≤28 days after the onset, as well as 94 373 in IS patients, were identified during the study period. In 2019, the ≤28 days case fatality rate in HS patients was 4.75 times that of IS patients (37.08% vs. 7.80%), as well as that 4.06 times in urban areas (30.13% vs. 7.43%) and 5.30 times in rural areas (42.63% vs. 8.05%), respectively. Thus, in rural areas, HS patients showed 41.49% higher ≤28 days case fatality rate than that in urban areas, as well as 8.34% higher in IS patients. Those ≤28 days case fatality in both stroke subtypes onset increased with age and reached the highest level in those aged 85 years and over. During the study period, HS and IS patients in each age group displayed significant decrease trend in ≤28 days case fatality rate (trend P<0.001). Compared with that in 2015, the age-standardized ≤28 days case-fatality in HS patients in 2019 decreased by 28.52%, which was more in urban areas (-34.27%) than that in rural areas (-23.19%). Meanwhile, IS patients experienced a 39.90% reduction in ≤28 days case fatality, which was much lower in urban areas (-31.62%) than in rural areas (-45.10%, all trend P<0.001). Conclusions:From 2015 to 2019, ≤28 days case fatality in both HS and IS patients decreased in China. Wide variations of ≤28 days case-fatality were evident in the level and trend in stroke subtype, age of patients, as well as urban and rural areas. More precise and comprehensive strategies for stroke prevention, treatment, and post-stroke management are urgently required in China.

Objective:To investigate the clinical efficacy of open arthrolysis in the treatment of posttraumatic elbow stiffness.Methods:A retrospective analysis was conducted on the data of 407 patients with post-traumatic elbow stiffness treated by open arthrolysis surgery in Shandong Provincial Hospital from January 2010 to January 2024. The cohort included 303 males and 104 females, with a mean age of 38.98±10.90 years (range, 18-72 years) and mean body mass index (BMI) of 24.32±3.29 kg/m 2 (range, 17.91-33.41 kg/m 2). There were 230 patients with right-sided elbow stiffness, 159 patients with left-sided elbow stiffness, and 18 patients with bilateral elbow stiffness. Initial injuries included 21 patients of isolated elbow dislocation; 25 patients of soft tissue injury; and 361 patients of initial intra-articular elbow fractures, among which there were 200 patients of multiple fractures, 87 patients of single distal humerus fracture, 43 patients of single proximal ulna fracture, and 31 patients of single radial head fracture. Initial injuries were treated non-surgically in 69 cases and surgically in 338 cases, among which 177 cases were retained with internal fixation. There were 334 preoperative patients complicated with heterotopic ossification and 73 patients without heterotopic ossification, with 99 patients undergoing early release (stiffness duration <6 months) and 308 patients undergoing late release (stiffness duration ≥6 months). Record the range of motion (ROM) of the elbow joint, forearm rotational range (FRR), visual analogue scale (VAS), Mayo elbow performance score (MEPS), modified Broberg-Morrey score (MBS), Oxford elbow score (OES), and disability of arm, shoulder and hand (DASH) score before and after surgery, and conduct comparative analysis. Results:All patients were followed up for an average of 41.86±10.27 months (range, 13-119 months). At 12 months postoperatively, elbow ROM improved from preoperative 33.7°±26.5° to 101.2°±24.0°, elbow FRR improved from preoperative 101.4°±53.5° to 138.9°±38.7°, the MEPS increased from 60.1±14.7 to 91.5±10.1, the BMS increased from 57.5±12.8 to 83.7±11.0, the OES decreased from 31.6±7.3 to 16.0± 4.6, the DASH score decreased from 38.8±13.9 to 10.1±9.5, and the VAS decreased from 3.0±2.3 to 0.9±1.1, with all changes showing statistical significance ( P<0.05). In patients with preoperative heterotopic ossification, postoperative mean flexion range was 120.1°±15.5° and elbow ROM was 102.6°±23.4°. In patients without preoperative heterotopic ossification, postoperative mean flexion range was 113.9°±15.6° and elbow ROM was 93.4°±26.4°. Statistically significant differences were observed between the two groups in postoperative flexion range and flexion-extension ROM. There were no statistically significant differences in the postoperative above-mentioned indicators between early and late release patients ( P>0.05). The supination range and elbow FRR in patients with multiple fractures were lower than those in patients with distal humerus fractures and proximal ulna fractures; the DASH score in patients with multiple fractures was higher than that in patients with proximal ulna fractures and radial head fractures; the OES score in patients with multiple fractures was higher than that in patients with proximal ulna fractures, and all differences were statistically significant ( P<0.05). Among 407 patients, complications included new-onset postoperative ulnar neuropathy in 61 cases, new heterotopic ossification in 11 cases, recurrent heterotopic ossification in 96 cases, elbow instability in 6 cases, and superficial surgical site infection in 2 cases. Conclusions:Open arthrolysis is an effective treatment option for post-traumatic elbow stiffness. Patients with preoperative heterotopic ossification have a greater postoperative flexion range and elbow flexion-extension range of motion. The surgical timing exerts no significant influence on the ultimate functional outcome of treatment in patients with post-traumatic elbow stiffness. Patients with different initial fracture sites exhibited significant differences in postoperative functional outcomes, including supination, DASH scores, and OES.