The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective To investigate the efficacy of continuous saline bladder irrigation(CSBI)after a single immediate instillation of chemotherapy(SIIC)in patients with low-and immediate-risk non-muscle-invasive bladder cancer(NMIBC)undergoing transurethral resection of bladder tumor(TURBT).Methods Clinical data of 211 patients with with low-and immediate-risk NMIBC,who underwent TURBT in our hospital during Jan.2004 and Dec.2019 were collected.The patients were divided into two groups according to whether CSBI was conducted after SIIC.The recurrence rate,progression rate,recurrence-free survival and progression-free survival of the two groups were compared.Cox univariate and multivariate regression analyses were used to investigate whether CSBI was a risk factor for recurrence and progression.Results There were no significant differences in baseline data,recurrence rate and progression rate between the two groups(P＞0.05).There was no significant difference in recurrence-free survival between the two groups,but the progression-free survival was shorter in CSBI group(x2=8.270,P=0.004).Multivariate Cox regression analysis indicated that diabetes(HR:2.240,95％CI:1.066-4.704,P=0.033)and multiple tumors(HR:3.060,95％CI:1.639-5.711,P＜0.001)were independent risk factors for recurrence and CSBI(HR:7.914,95％CI:1.710-36.632,P=0.008)was an independent risk factor for progression.Conclusion CSBI after SIIC may increase the risk of progression in patients with low-and immediate-risk NMIBC,but a larger sample size is needed for validation.

Background The serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. Objective To verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. Methods Based on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM_2.5 and PM₁₀ concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM_2.5, PM₁₀, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM_2.5, PM₁₀, and microorganisms. Results During the intervention period, the mean indoor concentrations of PM_2.5, PM₁₀, and culturable colonies were lower than those of the no-intervention period (P<0.01 or P<0.001). The ratios of indoor to outdoor concentration (I/O) of PM_2.5 and PM₁₀ during the intervention period were significantly lower than those of the no-intervention period (P<0.001), except the I/O of culturable colonies. Compared with the average concentration at 9:00, the average cleaning rates at 12:00 and 17:00 for PM_2.5 were 49.0% and 46.1%, for PM₁₀ were 49.7% and 45.4%, for airborne culturable colonies were 50.8% and 49.9%, respectively. The β diversity analysis showed that there were significant differences in composition at the level of species of bacteria, and at the levels of genus and species of fungi between the intervention and the no-intervention periods. The relative abundances of 10 species of bacteria such as Lactobacillus and 7 species of fungi such as Torula in the intervention period were significantly lower than those in the non-intervention period, but the relative abundances of fungi such as unclassified_f_cladosporiaceae, trichomerium, and cercospora were higher (P<0.05). For typical pathogenic bacteria, the relative abundances of Lactobacillus and Clostridium_sensu_stricto_1 during the intervention period were 73.5% and 86.9% lower than those in the no-intervention period, and the relative abundance of Talaromyces was 53.5% lower (P<0.05). Conclusion Low temperature plasma air purifier has a good purification effect on indoor PM_2.5, PM₁₀, and culturable colonies in highway toll booths, and likely a limited effect on some fungi.

Dura mater is a tough collagen connective tissue attached to inner surface of skull and wrapped around brain.As a buffer bridge between brain tissue and skull,its physiological function and role in skull development and repair have always been a focus of research.Recent studies have found that dura mater not only directly participates in skull development during skull growth,but also secretes a variety of cytokines that control the development of central nervous system.There are abundant material exchange and cell communication between the two.This article reviews the role of dura in development and repair of skull,and provides clues for further discovery of the relevant mechanisms of dura in development and repair of skull.

Objective To present the initial practice of a novel procedure for the surgical treatment of inguinal hernia-"lateral approach single-incision laparoscopic totally extraperitoneal(L-SILTEP)repair"in certain specific situations.Methods The clinical data of 110 inguinal hernia patients who underwent L-SILTEP in the First Affiliated Hospital of Ningbo University,Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine,and Shanghai East Hospital affiliated to Tongji University from June 2021 to March 2024 were collected retrospectively.Patients' demographics,surgical details,length of hospital stay,and postoperative outcomes were analyzed respectively.Results All surgeries were completed successfully and there was no conversion.The median surgical time was 55(41.25,70)mins and the intraoperative blood loss was 5(2,10)mL.In surgery,inferior epigastric artery injury occurred in 5 cases(4.5%)and spermatic cord injury occurred in 1 case(0.9%).The mean visual analog scale(VAS)scores pain assessment at 6,24,and 48 h after surgery were 3.0±0.8,1.9±0.7 and 1.1±0.4,respectively.The duration of hospital stay was(3.3±0.7)days.The most common postoperative complication was seroma,which occurred in 9 cases(8.2%).Additionally,extraperitoneal hematoma occurred in 1 case(0.9%)and scrotum effusion in 1 case(0.9%).Conclusions Generally,L-SILTEP is safe,feasible and effective.However,due to its advanced technique-demand,the application of L-SILTEP should be patient-specific and surgeon-specific.The successful implementation of this surgical procedure necessitates extensive training and meticulous attention to the surgical details.

Objective: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results: During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

Objective: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results: During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

Objective: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results: During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

Objective: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). Methods: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients’ clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. Results: During a mean follow-up of 5.5 years (range, 5–7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. Conclusion Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.