Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

AIM: To explore the possible mechanism of Xiaokeshu recipe in the treatment of type 2 diabetes mellitus (T2DM) by observing the effects of Xiaokeshu Recipe on serum inflammatory factors. METHODS: Male SPF-grade SD rats were fed with high-fat and high-sugar fodder combined with intraperitoneal injection of streptozotocin (STZ) to prepare the model of T2DM. The model rats were randomly divided into a model group,a metformin group, low and high-dose Xiaokeshu recipe groups, and a normal group was set up. After successful modeling, the metformin group and the Xiaokeshu recipe groups were treated with metformin and Xiaokeshu recipe by gavage respectively, normal saline was given by gavage in the normal group and the model group. The general living status of rats before and after treatment was observed. After 4 weeks of drug intervention, serum samples and ileum tissue of rats were collected for biochemical and Western blot. RESULTS: As compaed with the model group,the polydipsia and polyuria in the low and high-dose Xiaokeshu recipe and the metformin groups could be improved. As compaed with the model group, the levels of fasting blood glucose (FBG), fasting insulin (FINS) and interleukin-1β (IL-1β) of rats in the low-dose Xiaokeshu recipe group were decreased, but the differences were statistically insignificant (P0.05), the levels of FBG, FINS and IL-1β of rats in the high-dose Xiaokeshu recipe and the metformin groups were significantly decreased as compared with the the model group (P 0.05 or P0.01). As compaed with the model group, the levels of Lipopolysaccharide (LPS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the high-dose Xiaokeshu recipe and the metformin groups were decreased (P<0.05 or P<0.01). As compared with the model group, the expressions of toll-like receptor 4 (TLR4) and nuclear transcription factor (NF-κB) protein in ileal tissue were down-regulated in the low and high-dose Xiaokeshu Recipe and the metformin groups (P<0.05 or P<0.01). CONCLUSION: Xiaokeshu recipe may reduce the level of serum LPS, inhibit the TLR4/NF-κB signaling pathway, and reduce the release of inflammatory factors, thus improving insulin resistance and reducing the blood sugar of the body.

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Objective· To investigate whether vitamin E could reverse the disruptive effects of bisphenol A (BPA) on steroidogenesis and to explore the optimal vitamin E concentration.Methods· Rat primary granulosa cells were extracted and exposed to BPA (0,0.01,0.1,1,10,100 μmol/L).After 48 h of incubation,culture medium was collected and estradiol (E2) and progesterone (P4) were measured using ELISA kits.Then,granulosa cells were incubated with 5 μmol/L(average concentration in follicular fluid) or 25 μmol/L (high concentration in follicular fluid) vitamin E (α-tocopherol) or vitamin E (5 μmol/Lor 25 μmol/L) plus BPA (10 μmol/L or 100 μmol/L) for 48h,E2 and P4 were measured.Results· BPA at 10 μmol/L and 100 μmol/L suppressed E2 and P4 production in a dose-dependent manner (P＜0.05).Vitamin E at 25 μmol/L significantly increased E2 and P4 levels by (44.89±15.18) ％ and (43.33±8.82) ％(P＜0.05),respectively.Coincubation of the granulosa cells with BPA and vitamin E (5 μmol/L or 25 μmol/L) restored the productions of E2 and P4,which were not significantly different from the control group (P＞0.05).Conclusion· Vitamin E (5 μmol/L/25 μmol/L) could reverse BPA-induced reduction in steroid hormone production in rat ovary granulosa cells,and the antagonistic effect of 25 μmol/L vitamin E was more obvious than that of 5 μmol/L vitamin E.

OBJECTIVE:To analyze the risk factors of adverse reaction in children induced by Azithromycin for injection. METHODS:Data and medication of 428 children used Azithromycin for injection were retrospectively collected,and logistic re-gression method was used to analyze the risk factors of adverse reactions that likely to occur. RESULTS:In the 428 children,98 re-ported adverse reactions with incidence of 22.9%,among which,53 showed gastrointestinal adverse reactions (12.4%),22 showed pain in injection site(5.1%),12 showed phlebitis(2.8%),4 showed pruritus(0.9%),2 showed rash(0.5%),3 showed liver function abnormalities(0.7%),1 showed thrombocytopenia(0.2%)and 1 showed drowsiness(0.2%). According to adverse reactions diagnostic criteria,24 were sure,23 were very likely and 51 were possible. Logistic regression analysis showed younger age [OR=0.811,95% CI(0.754,0.842),P=0.000] and long duration [OR=0.1.357,95% CI(1.212,1.519),P=0.000] might the rick factors that caused adverse reactions. CONCLUSIONS:Younger age and long duration are the possible rick factors that caused adverse reactions in children after intravenous administration of azithromycin,close observation and controlling duration should be noticed to reduce the incidence of adverse reactions in children medication.

OBJECTIVETo explore the surgical strategy for postburn cervical scar contracture.

METHODSSixty-five patients with scar contracture as a result of burn injury in the neck were hospitalized from July 2013 to July 2014. Release of cervical scar contracture was conducted according to different demands of the 3 anatomic subunits of neck, i.e. lower lip vermilion border-supramaxillary region, submaxillary region, and anterior region of neck. After release of contracture, platysma was released. For some cases with chin retrusion, genioplasty with horizontal osteotomy was performed. The coverage of wound followed the principle of similarity, i.e. the skin tissue covering the wound in the neck should be similar to the characters of skin around the wound in terms of color, texture, and thickness. Based on this principle, except for the preschool children in whom skin grafting was performed, the wounds of the other patients were covered by local skin flaps, adjacent skin flaps, or free skin flaps.

RESULTSAll patients underwent release of scar and platysma, while 9 patients underwent genioplasty with horizontal osteotomy. Wounds were covered with local skin flaps in 32 patients, with adjacent skin flaps in 7 patients, with free skin flaps in 11 patients, and with skin grafts in 15 patients. All skin grafts and flaps survived. Good range of motion was achieved in the neck of all patients, with the cervicomental angle after reconstruction ranging from 90 to 120°. All patients were followed up for 6 to 24 months. Six patients who had undergone skin grafting were found to have some degrees of skin contracture, while none of the patients who had undergone flap coverage showed any signs of contracture recurrence.

CONCLUSIONSRestoration of the cervicomental angle is critical in the treatment of postburn cervical scar contracture, and the release of scar contracture should conform to the subunit principle. The coverage of wound should be based on the principle of similarity, with repair by skin flaps as the first choice, and skin grafting as the second choice. Satisfactory effect of repair would be achieved by following the above surgical principles.

Burns ; complications ; surgery ; Child ; Child, Preschool ; Cicatrix ; etiology ; surgery ; Contracture ; etiology ; surgery ; Free Tissue Flaps ; Humans ; Neck ; surgery ; Range of Motion, Articular ; Reconstructive Surgical Procedures ; methods ; Skin ; Skin Transplantation ; Superficial Musculoaponeurotic System ; Surgical Flaps ; Treatment Outcome

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis