BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.

Objective:To understand the current state of financial toxicity and suicide risk in head and neck cancer patients, to investigate the correlation between the level of financial toxicity and suicide risk in head and neck cancer patients, and to provide a basis for reducing the level of financial toxicity and the risk of suicide in head and neck cancer patients.Methods:A cross-sectional survey was conducted, from March 1 to July 31, 2022, 150 head and neck cancer patients were selected from Oncology Department of East Hospital Affiliated to Tongji Universityby by convenient sampling method. The survey was carried out by means of the general questionnaire, Comprehensive Score for Financial Toxicity based on the Patient-Reported Outcome Measures (COST-PROM), Cancer Suicide Risk Scale (CSRS), and then analysis the datum.Results:The score of COST-PROM of 150 head and neck cancer patients was (18.00 ± 6.12) points, and the score of CSRS of head and neck cancer patients was (36.31 ± 8.51) points. The total score of economic toxicity was significantly negatively correlated with the total score of suicide risk and its dimensions ( r values were -0.446 to 0.235, all P<0.05). The total score of suicide risk was negatively correlated with the total score of economic toxicity and the scores of each dimension ( r values were -0.446 to -0.251, all P<0.05). Conclusions:Patients with head and neck cancer were at higher risk of suicide, and financial toxicity was a significant contributing factor to suicide risk, with higher levels of financial toxicity associated with a higher risk of suicide. Reducing the level of financial toxicity in patients with head and neck cancer has important implications for reducing their risk of suicide.

The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.

Objective:To review the experience of closure of the left-main-bronchial stump fistula using endoscopic liner cutter staplers through the right thoracic approach and I stage or staged treatment for the left pyothorax.Methods:6 patients with the left-main-bronchial stump fistula after left pneumonectomy combined with pyothorax were treated by closing the left-main-bronchial stump using endoscopic liner cutter staplers through the right thoracic approach, and pleura was used to cover the distal and proximal incisional margin of the stump respectively. The thoracic T-tube drainage was used in the I stage or staged treatment for the left pyothorax.Results:All patients were survived without recurrence of the bronchopleural fistula. 4 patients were observed to have no recurrence of pyothorax when 1 patient had recurrence of pyothorax and was treated with intermittent T-tube drainage.1 patient operated with left-thoracic fenestration in the past was treated with drainage waiting for secondary operation.Conclusion:The right thoracic approach seemed to be a safer and more effective method than the transsternal transpericardial approach in cases with the left-main-bronchial stump fistula combined with pyothorax. The use of endoscopic liner cutter staplers reduced the risk of bleeding, infection and recurrence of fistula. The T-tube drainage in the I stage or staged treatment for the left pyothorax was considered to be an easier way for treatment.

Objective To explore the risk factors and short outcomes associated with late-onset sep-sis (LOS) in very low and extremely low birth weight infants.Methods Retrospective analysis were per-formed to predict risk factors for LOS in very low and extremely low birth weight infants (birth weight less than 1 200 g) admitted to NICU of Shengjing Hospital from Jan 2010 to Dec 2015.Infants with similar birth weight without LOS were as controls.We compared the characteristics of maternal and neonatal periods in both groups.Multivariable Logistic regression models were derived to predict LOS sepsis.Short outcomes of the infants were assessed.Results Total of 381 very low birth weight infants were admitted during the study period.LOS occurred in 138 infants(36.2%,138/381),who developed sepsis at a mean age of (19.8 ± 11.0)days;the mean gestational age,birth weight and hospitalization time were(29.4 ± 2.1)week,1 064 (953,1 126)g and 55(43,72)d.Other 243 cases were control,mean gestational age,brith weight and hospi-talization time were(29.3 ± 2.0)week,1 060(955,1 144)g and 49(37,63)d.Ninety-seven cases had posi-tive blood culture(70.3%,97/138) in LOS group.Out of the 138 cases of LOS,8 cases(5.8%,8/138) died from their sepsis with a positive blood culture.Infants with LOS were more likely to have a long-term use of ventilation and peripherally inserted central catheteh(PICC),the failure of early enteral feeding,delayed com-plete enteral feeding time and the longer hospital stays compared to uninfected infants.Multivariate Logistic regression analysis showed that long-term use of PICC(OR 1.039,95%CI 1.012-1.067,P=0.004)was an independent risk factor for LOS in very low birth weitht infants. Septic infants,compared with nonseptic infants,had significantly more serious morbidity,including white matter damage(20.3% vs.10.3%),necro-tizing enterocolitis(9.4% vs.2.9%),retinopathy of prematurity(10.9% vs.3.7%),and cholestatic jaun-dice(19.6% vs.11.9%)(P<0.05).Conclusion A number of factors are related to LOS.LOS is associated with poor prognosis of preterm infants.Long-time PICC is a risk factor for LOS.

Algorithms ; Crystallography, X-Ray ; Disulfides ; chemistry ; Models, Molecular ; Protein Conformation ; Proteins ; chemistry

Objective To investigate the effect of astrocyte-derived microparticles on intracellular free calcium concentration in umbilical vein endothelial cells (UVECs).Methods Brain astrocytes were first isolated from 24 h new-born Sprague-Dawley rats and cultured in vitro.Then,they were stimulated with calcium ionophore,A23187,and microparticles were extracted by fractional centrifugation and verified by electron microscopy.UVECs cultured in vitro were divided into control group,nimotop group,and low,median and high concentrations ofmicroparticles groups;cells from nimotop group were pretreated with 10 μL nimotop for 10 min;cells from the later 4 groups were given 1×108,0.5×108,1×108,and 2× 108/mL microparticles respectively;cells from the control group were given the same volume of medium.Ten min after cultivation,they were loaded with fluorescent probe Fluo3-AM,respectively.Later,the concentration of Ca2+ in UVECs was measured by confocal laser scanning microscope and flow cytometry.Results The isolation and in vitro culture methods for rat astrocytes provided stable and reliable results.With A23187 stimulation and fractional centrifugation,astrocyte derived microparticles were available for extraction.Laser scanning confocal microscope indicated that the intracellular fluorescence intensity in the control group was the lowest;after incubating UVECs with low,median and high concentrations of astrocyte-derived microparticles,the intracellular fluorescence intensity increased,and it increased following the concentrations of astrocyte-derived microparticles;pretreatment with nimotop could moderately decrease the intracellular fluorescence intensity,but that in the nimotop group was still higher than that in the control group.The mean fluorescence values for intracellular free Ca2+ were 51 866,57 996 and 73 630,respectively,in the low,median and high concentrations of microparticles groups,which showed statistically significant increase as compared with that from the control group (45 759,P＜0.05).When nimotop was applied to the cells,it blocked the influx of calcium ions and the measured value was significantly changed to 49843,enjoying significant difference as compared with that from the low,median and high concentrations of microparticles groups (P＜0.05).Conclusion Astrocyte-derived microparticles are capable of increasing the intracellular free calcium concentration in UVECs,and the effects can be blocked by nimotop.

Objective · To observe the effects of custom made fiber posts on the fracture resistance of young permanent teeth treated with calcium hydroxide for different time. Methods · Forty-five extracted human young permanent teeth (premolar) were selected and randomly assigned to 9 groups.One group was the control group and the rest 8 groups were treated with conventional root canal preparation. Of these 8 groups, 4 groups (F Ⅰ , F Ⅲ , F Ⅵ ,FⅨ ) were restored by custom made fiber posts after being treated with calcium hydroxide for 1, 3, 6, and 9 months respectively, and other 4 groups (C Ⅰ ,CⅢ , C Ⅵ , C Ⅸ ) were not restored by custom made fiber posts. All samples underwent fracture strength tests and their fracture modes were analyzed for the possibility of second repair. Results · The fracture load was decreased with the treatment time after being treated with calcium hydroxide for 1 month (P<0.01). The fracture loads in groups restored by custom made fiber posts were increased after being treated with calcium hydroxide for 6 and 9 months (P<0.05, P<0.01). After being treated with calcium hydroxide for 1 month, groups restored by custom made fiber posts were likely to have fracture modes that facilitate the second repair as compared with groups not restored by custom made fiber posts (P<0.05). Conclusion · The restoration by custom made fiber posts can increase the fracture resistance of young permanent teeth treated with calcium hydroxide for medium and long term ( ≥ 1 month).