Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Bedridden patients mostly use the back cushion object,raise the bedside position,and other methods to obtain the semi-decumbent position.However,the existing methods have shortcomings such as insufficient execution,wrong angle estimation,weak consciousness,forgetting,decreased comfort,easy to cause pressure sore and aspiration pneumonia.To solve the shortcomings of the existing eating position placement method,the department of geriatric medicine team of Tongxiang City Hospital of Traditional Chinese Medicine designed a bed-rest pillow for bed patients to eat or other requirements of semi-lying position,and obtained the National Utility Model Patent of China(patent number:ZL 202122859891.4).This device places the pillow on a flat bed,with the back of the pillow next to the head of the bed for support and to prevent sliding.The patient was placed in a retainer slot,head in the first retainer slot,shoulder and back in the second retainer slot,waist and abdomen in the third retainer slot,and hands on the armrests on both sides of the pillow.The use of pillows for bedridden patients is simple and easy to learn,convenient,economical and practical,time-saving and labor-saving,and convenient supervision and inspection,which can reduce complications such as aspiration and pressure ulcers,thereby reducing the economic burden of the patient,improving the quality of life,and improving the satisfaction of patients and their families,and is worthy of clinical promotion and use.

Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses. In this review, we summarize and compare the advantages and disadvantages of Alum and NanoAlum in these properties and their performance as adjuvants. Moreover, we propose the key features for ideal adjuvants and demonstrate that LDH NanoAlum is a promising candidate by summarizing its current progress in immunotherapeutic cancer treatments. Finally, we conclude the review by offering our integrated perspectives about the remaining challenges and future directions for NanoAlum's application in preclinical/clinical settings.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Objective:To investigate the preventive effects of intravenous N-acetylcysteine(NAC)administration on contrast-induced nephropathy(CIN)following coronary intervention in elder patients with coronary heart disease(CHD)complicated with moderate to severe renal dysfunction.Methods:In this retrospective study, 242 elderly patients with CHD and moderate to severe renal insufficiency hospitalized in the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University and undergone coronary angiography from January 2018 to February 2022 were included and divided into two groups: the treatment group(100 cases)receiving NAC plus a continuous intravenous drip of 0.9% sodium chloride solution before and after surgery and the control group(142 cases)treated with only a continuous intravenous drip of 0.9% sodium chloride solution.To ensure the comparability of important baseline data between the two groups, a 1∶1 propensity score matching analysis was used, and 70 patients in each group were finally included.Pre-and post-operative serum creatinine(Scr)and blood urea nitrogen(BUN)values were recorded, the endogenous creatinine clearance(Ccr)and estimated glomerular filtration rate(eGFR)were calculated, and the incidences of CIN and changes in renal function indicators were compared between the two groups.Results:After coronary intervention, the incidence of CIN in the treatment group was significantly lower than that in the control group(1/70 or 1.4% vs.8/70 or 11.4%, P=0.033). In the treatment group, Scr[(186.01±36.62)μmol/L vs.(195.84±36.39)μmol/L, t=4.957, P<0.001]and BUN[(13.97±2.89)mmol/L vs.(14.84±2.85)mmol/L, t=5.206, P<0.001]decreased, while Ccr[(31.84±6.54)ml/min vs.(30.08±5.65)ml/min, t=-5.076, P<0.001]and eGFR[(31.60±6.93)ml·min -1·1.73m -2vs.(29.82±5.92)ml·min -1·1.73m -2, t=-5.200, P<0.001]increased, compared with pre-operative levels.In the control group, Scr[(186.65±27.28)μmol/L vs.(182.53±22.08)μmol/L, t=-1.783, P=0.079]and BUN[(17.57±3.33)mmol/L vs.(17.13±3.35)mmol/L, t=-2.234, P=0.029]increased, but Ccr[(30.57±6.37)ml/min vs.(31.06±6.01)ml/min, t=1.435, P=0.156]and eGFR[(30.76±6.46)ml·min -1·1.73m -2vs.(31.26±6.02)ml·min -1·1.73m -2, t=1.436, P=0.156]decreased, compared with pre-operative levels, and there was no significant difference except BUN(all P>0.05). Conclusions:For elderly patients with coronary heart disease complicated with moderate to severe renal insufficiency, the use of NAC before and after coronary intervention can reduce the risk of CIN and help improve renal function.

Objective To clarify the role of human β-defensin2 ( hBD2) on preventing oxidized low-density lipoprotein (OX-LDL) induced human leukemic monocyte (THP-1) foaming.Methods The monocyte foaming model was established using THP-1 cell induced by OX-LDL and the model was identified by oil red staining.The hBD2 was overexpressed on THP-1 cells by using lentivirus system and the effect of hBD 2 overexpression on THP-1 cell foaming induced by OX-LDL was detected.The levels of inflammatory factors including tumor necrosis factor (TNF)-α, interleukin (IL)-1βand IL-6 in cell supernatant of each group were detected by enzyme-linked immunosorbent assay ( ELISA).Differences between the groups were compared by using the t test.Results The gene transfection efficiency of the cells was close to 100%at 72 h after infection. The hBD2 protein levels were 0.122 ±0.024 in the control group, 0.123 ±0.022 in Lv-control infection group and 0.981 ±0.183 in Lv-hBD2 infection group; and the level in control group was statistically higher than that in hBD-2 infection group (t＝-3.175, P＝0.007).The relative levels of hBD2 mRNA at 72 h after virus infection were 0.131 ±0.021 in control group, 0.128 ±0.022 in Lv-control group and 1.001 ±0.105 in Lv-hBD2 infection group; and the level in control group was statistically higher than that in hBD-2 infection group (t＝-7.213, P＝0.003).The results of oil red staining showed that OX-LDL inducing THP-1 cells for 72 h could significantly induce lipid accumulation in cells.Overexpression of hBD2 could effectively inhibit lipid accumulation in THP-1 cells induced by OX-LDL.The expression of hBD2 mRNA in THP-1 group was significantly higher than that in THP-1+OX-LDL group (t＝3.237, P＝0.004); and the difference was also significant when comparing THP-1+Lv-hBD2+OX-LDL group with THP-1+OX-LDL group (t＝-6.021, P＝0.003).The level of hBD2 protein in THP-1 group was significantly higher than that in THP-1+OX-LDL group (t＝0.314, P＝0.006); and the difference was also significant when comparing THP-1+Lv-hBD2+OX-LDL group with THP-1+OX-LDL group (t＝-4.061,P＝0.007).The levels of TNF-α, IL-1βand IL-6 in the supernatant of THP-1 cells induced by OX-LDL for 72 h were significantly increased compared with those in THP-1group (t＝-3.825,-2.017 and -3.551, respectively; P＝0.007, 0.004 and 0.005, respectively). The levels of TNF-α, IL-1βand IL-6 in THP-1+Lv-hBD2+OX-LDL group were significantly lower than those in THP-1+OX-LDL group ( t＝4.132, 3.681, and 2.991, respectively; P＝0.003, 0.002, and 0.007, respectively).Conclusions hBD2 can effectively inhibit THP-1 foaming induced by OX-LDL, which may be related to its inhibition of inflammatory response.

Objective: To investigate the changes of ³¹P-MRS in denervated skeletal muscle at 7.0 T MR system. Methods: In the experiment group, a total of 18 male Sprague-Dawley rats aged 6-8 weeks old and weighing 200-250 g were obtained. The right posterior femoral nerve were transected, and the proximal stumps were ligated by using 5-0 nylon stitches to preclude spontaneous repair. A sham surgery (incision and exploration of the nerve) was performed at the same time (n=6). Before rat model established and at varying times after initial surgery (3 d, and 1, 2, 4, 6, and 8 weeks). ³¹P-MR spectra of rat quadriceps femoris were acquired on 7.0 T Agilent small animal MR imaging system. We quantified the phosphocreatine (PCr), adenosine triphosphate(β-ATP), and inorganic phosphate (Pi) using Creatine phosphate disodium salt(10 mmol/L) as an external standard. The ratios, include PCr/Pi, Pi/β-ATP, PCr/β-ATP, PCr/(PCr+Pi) and Pi/(PCr+Pi) were quantified in jMRUI. All data were analyzed by one way analysis of variance (ANOVA) with posttest inter-group comparisons using Bonferroni test. Comparative analysis methods between the experimental and control group were performed via independent samples t test. P<0.05 was considered as statistically significance. Results: The average measured concentrations of β-ATP, PCr, and Pi in control groups were (6.654±0.178) μmol/g, (25.656±0.738) μmol/g, and (1.594±0.096) μmol/g, respectively. There were significant statistically differences in β-ATP, PCr, Pi, PCr/Pi, PCr/PCr+Pi,Pi/PCr+Pi between the study and control group(P<0.05) at any measurement time point after denervation. Pi/β-ATP,PCr/β-ATP and pHi in the experimental group significantly statistically differed from those of the control group (all P<0.05)at each time point except on day 3 after operation. The total concentrations of β-ATP and PCr were reduced by 11.5% and 19.7% respectively on day 3. Thereafter, β-ATP and PCr declined rapidly by 63.1% and 68.8% at week 4 respectively, then decreased slowely by 74.0%和82.3% till week 10. The change of PCr/Pi is similar to β-ATP and PCr, but more remarkable. Pi, Pi/PCr+Pi, Pi/ATP showed a progressively increase till week 10. The intra-cellular pH (pHi) of normal rat muscles was 7.033±0.017, While the pHi gently in experiment rat muscles decreased during the entire experiment. Conclusion ³¹P-MRS with 7.0 T can quantify the temporal changes of energy metabolism and pHi in normal and denervated rat muscles. It shows that the dysfunction of energy metabolism are progressive with time and that they begin within a short period following the nerve section, the change of β-ATP, PCr, PCr/Pi take place primarily within 4 weeks after denervation. β-ATP, PCr, and PCr/Pi may be potential biomarkers of energy metabolism in the evaluation of denervated muscle atrophy.

Objective To investigate the efficacy of relaparoscopic common bile duct exploration in choledocholithiasis.Methods 50 patients who underwent LC/OC/LCBDE/OCBDE for biliary surgery with choledocholithiasis were randomized into two groups:Group A (n ＝25) laparoscopic approach and Group B (n =25) open approach.The operation time,hospital stay,cost of hospitalization and postoperative complications were compared.Results There was no significant difference in the operation time,liver functional index,postoperative bile leakage rate and cost of hospitalization between the two groups.The postoperative hospital stay in group A was shorter than that in group B (7.1 ± 1.5 vs 12.4 ±4.3 days,P ＜0.05),as was the volume of intraoperative blood loss (58.3 ± 24.2 ml vs 108.6 ± 35.7 ml,P ＜ 0.05),recovery of gastrointestinal function (26.3 ±3.6 vs 58.2 ±6.3 hours,P ＜0.05),postoperative analgesia (7/25 vs 17/25,P＜0.05) and wound infection rate (1/25 vs 6/25,P＜0.05).Conclusions Relaparoscopic commonbile duct exploration for recurrent choledocholithiasis appeared to be a safe,feasible,and efficacious procedure when carried out by expert laparoscopic surgeons.The procedure is worth promoting.

Objective To study the main risk factors related to the incidence of tuberculosis in China and to provide di -rections and basis for the protection of tuberculosis .Methods The results of 25 studies on the main risk factors of tubercu-losis of Chinese people from 2000 to 2012 were analyzed by meta-analysis method .Results The pooled odds radio values and 95%CI of history of exposure to pulmonary tuberculosis , smoking, marriage, contact with people, Bacille Calmette-Guerin (BCG)vaccination scar, BCG vaccination, low body mass index(BMI) , family history of tuberculosis, exposure to dust and to chemical fumes under working conditions were as follows:3.14(2.74-3.59),1.23(1.14 -1.33),3.05 (2.10-4.45),2.08(1.76-2.26),0.39(0.32 -0.47),0.58(0.46 -0.73),2.95(2.40 -3.64),2.56(1.82 -3.59),2.58(2.04-3.26),and 4.81(1.99-11.60).Conclusion Then History of exposure to pulmonary tuberculosis , smoking, marriage, contact with people , low BMI, family history of tuberculosis , exposure to dust and to chemical fumes under working conditions are considered to be the risk factors of pulmonary tuberculosis .While BCG vaccination scar and BCG vaccination are considered to be the protective factors of pulmonary tuberculosis .

Objective To investigate the changes of CD4+ CD25+ regulatory T lymphocyte (Treg) and expressions of folkhead helix transcription factor 3 (FoxP3) in intestinal mucosa in human immunodeficiency virus (HIV) infected patients. Methods Twenty-one HIV infected patients and 17 control subjects without HIV infection were included in this study. The expression of FoxP3, which was considered as a specific marker of CD4+ CD25 + Treg, was detected in intestinal mucosa specimens from HIV infected patients by immunohistochemistry. Meanwhile, the in situ expression of CD4+ T lymphocyte was also determined by immunohistochemistry. The data were analyzed by t test. Results The positive labeling index of CD4+ T lymphocyte in intestinal mucosa was significantly lower in HIV infected patients compared to the controls (11. 56%±4. 44% vs 43. 49% ±8. 90% ,t=-11. 86,P<0. 01). The positive labeling index of FoxP3 in intestinal mucosa was also significantly lower in HIV infected patients compared to the controls (0.46% ± 0.20% vs 1. 18% ± 0. 44% ,t= - 5. 98,P<0.01). Conclusion The depletion of CD4+ CD25+ Treg is accompanied with the depletion of CD4 + T lymphocyte and the reduction of FoxP3 expression in intestinal mucosa of HIV infected patients.