Objective:To investigate the clinicopathological characteristics of adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP).Methods:A total of 71 cases craniopharyngioma, included 52 cases of ACP and 19 cases of PCP, diagnosed at the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China from September 2019 to November 2023 were collected. Clinical pathological data were analyzed, immunohistochemical staining was performed, and mutations in the CTNNB1 and BRAF V600E genes were examined to identify differences between ACP and PCP.Results:The ACP cohort comprised 27 male and 25 female patients, with an age at onset ranging from 6 to 70 years, mean age (42.0±18.3) years. In contrast, the PCP group included 15 males and 4 females, with an age at onset spanning 28 to 74 years, mean age (51.0±13.3) years. The ACP group more commonly showed calcifications on imaging than the PCP group [92.3% (48/52) versus 11/19]. Partial tumor resection and the maximum diameter of the tumor were important factors affecting the recurrence of ACP. Whorled cell clusters, wet keratinization, stellate reticulum, cysts, and calcification were more often seen in ACP than PCP ( P<0.05). Immunohistochemically, all (100%,52/52) of the ACP showed nuclear β-catenin expression, with varying degrees of expression in the nodular whorls, and scattered cytoplasmic β-catenin expression. The BRAF V600E expression was found in the cytoplasm of all (19/19) PCP cases, but only non-specific BRAF V600E nuclear positivity was observed in ACP cases. Molecular testing showed that the mutation rate of the CTNNB1 gene in ACP was 22.7% (5/22), and the mutation rate of the BRAF V600E in PCP was 19/19. Conclusions:ACP and PCP have different age at onset, radiological features, histopathological morphology, and genetic alterations. Proper use and interpretation of immunohistochemical results can help distinguish between ACP and PCP, while molecular testing can be used as an auxiliary diagnostic modality.

Objective:To investigate the clinicopathological characteristics of adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP).Methods:A total of 71 cases craniopharyngioma, included 52 cases of ACP and 19 cases of PCP, diagnosed at the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China from September 2019 to November 2023 were collected. Clinical pathological data were analyzed, immunohistochemical staining was performed, and mutations in the CTNNB1 and BRAF V600E genes were examined to identify differences between ACP and PCP.Results:The ACP cohort comprised 27 male and 25 female patients, with an age at onset ranging from 6 to 70 years, mean age (42.0±18.3) years. In contrast, the PCP group included 15 males and 4 females, with an age at onset spanning 28 to 74 years, mean age (51.0±13.3) years. The ACP group more commonly showed calcifications on imaging than the PCP group [92.3% (48/52) versus 11/19]. Partial tumor resection and the maximum diameter of the tumor were important factors affecting the recurrence of ACP. Whorled cell clusters, wet keratinization, stellate reticulum, cysts, and calcification were more often seen in ACP than PCP ( P<0.05). Immunohistochemically, all (100%,52/52) of the ACP showed nuclear β-catenin expression, with varying degrees of expression in the nodular whorls, and scattered cytoplasmic β-catenin expression. The BRAF V600E expression was found in the cytoplasm of all (19/19) PCP cases, but only non-specific BRAF V600E nuclear positivity was observed in ACP cases. Molecular testing showed that the mutation rate of the CTNNB1 gene in ACP was 22.7% (5/22), and the mutation rate of the BRAF V600E in PCP was 19/19. Conclusions:ACP and PCP have different age at onset, radiological features, histopathological morphology, and genetic alterations. Proper use and interpretation of immunohistochemical results can help distinguish between ACP and PCP, while molecular testing can be used as an auxiliary diagnostic modality.

OBJECTIVE To observe the regulation of aerobic oxidation mediated by HIF-1α/PDHK1 pathway by PNS, and to explore its mechanism of promoting the differentiation of Naive CD4+T cells into Treg cells. METHODS Naive CD4+T cells were isolated from the spleen of C57BL/6 mice by magnetic beads and induced to differentiate into Treg cells for in vitro culture. Naive CD4+T cells were divided into PNS treatment group(5, 10, 20 μg·mL−1), PNS combined with HIF-1α inhibitor(PX-478) group, and the control group was set up. The proportion of Treg cells differentiation was detected by flow cytometry. The expression of HIF-1α and PDHK1 protein was detected by Western blotting. The expression of HIF-1α, PDHK1 and FOXP3 mRNA was detected by real-time fluorescence quantitative PCR. The level of IL-10 in cell culture supernatant was detected by enzyme-linked immunosorbent assay. RESULTS PNS could significantly increase the proportion of Treg cells and the secretion level of IL-10, and increase the expression of FOXP3 mRNA in cells. At the same time, the expression of HIF-1α and PDHK1 protein and mRNA was inhibited. When the cells were treated with 10 μmol·L−1 PX-478 and then treated with 10 μg·mL−1 PNS, the expression of PDHK1 and FOXP3 and the differentiation ratio of Treg cells were not significantly different from those treated with 10 μmol·L−1 PX-478 alone. CONCLUSION PNS can reduce the expression level of PDHK1 by HIF-1α to enhance the aerobic oxidation of Naive CD4+T cells and promote their differentiation into Treg cells.

Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.

Intestinal microorganisms and their metabolites are involved in the pathogenesis and progression of various cardiovascular diseases,especially in the progression of heart failure.This paper mainly discussed the gut microbial metabolites trimethylamine oxide(TMAO)participated in the pathological process of heart failure,and application value of TMAO in heart failure patients.This paper introduced the change characteristics of intestinal flora and its metabolites in heart failure patients,illu-minated the TMAO-mediated inflammatory response,and the related signal pathways and mechanism of myocardial hypertrophy and heart failure.High levels of TMAO are associated with poor outcomes in patients with heart failure indicating a good predictive value for the prognosis of heart failure.Regulating TMAO levels through diet,probiotics and prebiotics,antibiotics,fecal transplan-tation,and other pathways is expected to be a potential treatment for heart failure.

OBJECTIVE To investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）. METHODS The naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells. RESULTS Compared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）. CONCLUSIONS Catalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.

Objective:To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors.Methods:Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed.Results:Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing′s syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas.Conclusions:Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

Objective:To evaluate the efficacy of oliceridine for patient-controlled intravenous analgesia (PCIA) after bone tumor resection.Methods:In this prospective randomized controlled study, 72 patients of either sex, aged 18-64 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, who underwent elective bone tumor resection under general anesthesia, were selected and divided into 2 groups ( n=36 each) by the random number table method: sufentanil group (group S) and oliceridine group (group O). Combined intravenous-inhalational anesthesia was used in both groups. PCIA was performed from the end of surgery until 48 h after surgery. PCIA solution contained sufentanil 2 μg/kg in normal saline 100 ml in group S and oliceridine 0.4 mg/kg in normal saline 100 ml in group O. The background infusion rate was 2 ml/h, the bolus dose was 2 ml, the lockout interval was 15 min, and the maximum dose per hour was 10 ml in both groups. Flurbiprofen ester 50 mg was intravenously injected as rescue analgesic after operation when numerical rating scale score at rest≥4 or numerical rating scale score during activity≥7. The number of effective pressing times of patient-controlled analgesia (PCA), total pressing times of PCA, consumption of analgesics and requirement for rescue analgesia were recorded within 48 h after operation. Ramsay sedation scores were recorded at 2, 6, 12, 24 and 48 h after surgery. The occurrence of adverse reactions and requirement for rescue antiemetic within 48 h after surgery were recorded.The 15-item quality of recovery scale scores were assessed at 24 h before surgery and 24 and 48 h after surgery. The patient satisfaction score and satisfaction rate were recorded. Results:Compared with group S, the number of effective pressing times of PCA, total pressing times of PCA and consumption of analgesics were significantly reduced within 48 h after operation, the Ramsay sedation score was significantly increased at 12 h after surgery, the incidence of nausea and vomiting and rescue antiemetic rate were decreased, and the 15-item quality of recovery scale scores, satisfaction score and satisfaction rate were increased in group O ( P<0.05). There were no significant differences in the rate of rescue analgesia and incidence of respiratory depression, dizziness, pruritus and urinary retention within 48 h after operation ( P>0.05). Conclusions:Oliceridine has similar effect to sufentanil for postoperative PCIA, reduces the development of postoperative nausea and vomiting, improves satisfaction, and promotes early postoperative recovery when used in the patients undergoing bone tumor resection.

Objective:To evaluate the efficacy of oliceridine for patient-controlled intravenous analgesia (PCIA) after bone tumor resection.Methods:In this prospective randomized controlled study, 72 patients of either sex, aged 18-64 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, who underwent elective bone tumor resection under general anesthesia, were selected and divided into 2 groups ( n=36 each) by the random number table method: sufentanil group (group S) and oliceridine group (group O). Combined intravenous-inhalational anesthesia was used in both groups. PCIA was performed from the end of surgery until 48 h after surgery. PCIA solution contained sufentanil 2 μg/kg in normal saline 100 ml in group S and oliceridine 0.4 mg/kg in normal saline 100 ml in group O. The background infusion rate was 2 ml/h, the bolus dose was 2 ml, the lockout interval was 15 min, and the maximum dose per hour was 10 ml in both groups. Flurbiprofen ester 50 mg was intravenously injected as rescue analgesic after operation when numerical rating scale score at rest≥4 or numerical rating scale score during activity≥7. The number of effective pressing times of patient-controlled analgesia (PCA), total pressing times of PCA, consumption of analgesics and requirement for rescue analgesia were recorded within 48 h after operation. Ramsay sedation scores were recorded at 2, 6, 12, 24 and 48 h after surgery. The occurrence of adverse reactions and requirement for rescue antiemetic within 48 h after surgery were recorded.The 15-item quality of recovery scale scores were assessed at 24 h before surgery and 24 and 48 h after surgery. The patient satisfaction score and satisfaction rate were recorded. Results:Compared with group S, the number of effective pressing times of PCA, total pressing times of PCA and consumption of analgesics were significantly reduced within 48 h after operation, the Ramsay sedation score was significantly increased at 12 h after surgery, the incidence of nausea and vomiting and rescue antiemetic rate were decreased, and the 15-item quality of recovery scale scores, satisfaction score and satisfaction rate were increased in group O ( P<0.05). There were no significant differences in the rate of rescue analgesia and incidence of respiratory depression, dizziness, pruritus and urinary retention within 48 h after operation ( P>0.05). Conclusions:Oliceridine has similar effect to sufentanil for postoperative PCIA, reduces the development of postoperative nausea and vomiting, improves satisfaction, and promotes early postoperative recovery when used in the patients undergoing bone tumor resection.