Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Objective To explore the effect of Wenyang Huazhuo Tongluo recipe on pulmonary microvascular injury in mice with scleroderma based on mitophagy.Methods Fifty mice were randomly divided into blank control group(0.9％NaCl,by gavage),control group(0.9％NaCl,by gavage),model group,Wenyang Huazhuo Tongluo recipe group(47mg·kg-1·d-1 Wenyang Huazhuo Tongluo recipe by gavage),positive control group(10 mg·kg-1·d-1 KC7F2 dissolved in phosphate buffer solution intraperitoneal injection),continuous administration for 4 weeks.The expression levels of in vitro membrane translocation enzyme 20(TOMM20),hypoxia inducible factor-1α(HIF-1α),B cell lymphoma-2/adenovirus E1B-19 kDa interacting protein 3(BNIP3),PTEN inducible muscle enzyme protein 1(PINK1)and E3 ubiquitin ligase(Parkin)in lung tissue were detected by immunohistochemistry(IHC).Western blot(WB)was used to detect the expression levels of mitophagy-related proteins(TOMM20,LC3B)and HIF-1α/BNIP3/PINK1/Parkin pathway proteins in pulmonary microvascular endothelial cells.Results The relative content of HIF-1α in microvascular endothelial cells of lung tissue in the control group,model group,Wenyang Huazhuo Tongluo recipe group and positive control group were 0.17±0.02,0.98±0.01,0.66±0.03 and 0.48±0.01;the relative content of BNIP3 were 0.40±0.02,0.74±0.01,0.56±0.01 and 0.60±0.02;the relative content of PINK1 were 0.26±0.04,0.88±0.01,0.65±0.02 and 0.67±0.02;the relative contents of Parkin were 0.33±0.02,0.89±0.01,0.65±0.02 and 0.77±0.02;the relative contents of TOMM20 were 1.10±0.02,0.58±0.01,1.02±0.01 and 0.98±0.03;the relative contents of LC3B-Ⅰ/LC3B-Ⅱ were 0.24±0.01,0.80±0.01,0.53±0.02 and 0.70±0.02,respectively.The content of HIF-1α,BNIP3,PINK1,Parkin and LC3B-Ⅰ/LC3B-Ⅱ in model group was higher than those in control group.Wenyang Huazhuo Tongluo recipe can effectively reduce its content.The content of TOMM20 in the model group was lower than that in control group,and Wenyang Huazhuo Tongluo recipe can effectively increase its content.Conclusion Wenyang Huazhuo Tongluo recipe may inhibit mitophagy and improve SSc pulmonary microvascular injury by increasing TOMM20 and inhibiting the protein expression of LC3B and HIF-1α/BNIP3/PINK1/Parkin signaling pathway.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

OBJECTIVE: To compare the clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle anddistal tibia fractures. METHODS: The clinical data of sixty patients with middle and distal tibia fractures admitted between January 2019 and November 2022, were retrospectively analyzed. These patients were categorized into external fixation group (n=30) and internal fixation group (n=30). There were 18 males and 12 females in the external fixation group, with an average age of (49.29±2.35) years old. Among them, 14 patients presented with fractures on the left side, and 16 patients presented with fractures on the right side. Closed reduction, arched wire, and semi-circular external fixator were used for treatment. There were 20 males and 10 females in the internal fixation group, with an average age of (48.96±1.87) years old. Among them, 15 patients presented with fractures on the left side, and 15 patients presented with fractures on the right side. MIPPO technique was used for the treatment. Perioperative parameters, including time injury to surgery, surgical duration, incision length, intraoperative bleeding, time to active activity, and incision healing level, were compared between the two groups. Clinical outcomes were also assessed, including Johner-Wruhs scores, time to minimum pain-adapted full weight-bearing, visual analog scale (VAS), SF-36 scale, and complications. RESULTS: The external fixation group exhibited a significantly shorter incision length (1.36±0.86) cm and lower intraoperative bleeding (10.83±5.73) ml compared to the internal fixation group (12.74±3.12) cm and (86.47±8.90) ml, respectively(P<0.05). The postoperative active activity time (1.50±0.54) days and minimum pain-adapted full weight-bearing activity time(108.87±3.43) days in the external fixation group were slightly delayed than the internal fixation group(1.15±0.98) days and (105.27±3.68) days, respectively(P<0.05). Over a mean postoperative follow-up duration of (6.23±1.89) months, both groups showed improved VAS and SF-36 scale scores. There were no statistically significant differences in VAS and SF-36 scale scores 1, 3, 6 months post-operatively between the two groups(P>0.05). The intraoperative surgical time in the external fixation group (35.42±9.31) minutes was shorter than that in the internal fixation group(74.22±7.81) minutes (P<0.05). There was no intraoperative vascular or nerve injury, nor postoperative skin necrosis in the external fixation group. However, skin necrosis was observed in 6 patientsin the internal fixation group, representing a statistically significant difference (P<0.05). CONCLUSION Both external fixation and plate internal fixation are effective methods for the treatment of middle and distal tibia fractures. External fixation exhibits the advantage of less surgical trauma and a lower incidence of complications.
Female ; Male ; Humans ; Middle Aged ; Retrospective Studies ; Tibia ; Treatment Outcome ; Ankle Fractures ; Tibial Fractures/surgery* ; External Fixators ; Pain ; Necrosis

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

ObjectiveWhether blood urea nitrogen （BUN） can help increase risk stratification of simplified pulmonary embolism severity index （sPESI） in intensive care unit （ICU） still remains unknown. MethodsA total of 250 patients diagnosed as acute pulmonary embolism （APE） at ICU admission from medical information mart for intensive care Ⅲ database （MIMIC） were included in this retrospective study. The 30-day mortality was defined as the primary outcome. The optimal cut-off values of BUN and sPESI were calculated based on the maximum Youden index of receiver operating characteristic （ROC） curves. The Kaplan-Meier curves were used to evaluate the risk stratification ability of BUN， sPESI， and their combinations in the total cohort and subgroups. ResultsBUN and sPESI were both independent predictors for the 30-day mortality. The optimal cut-off value of BUN was 21.5 mg/dL and that of sPESI was 2.5. The 30-day mortality was 41.38% in high-risk group with BUN ≥21.5 mg/dL and sPESI ≥3， which was higher than that in group with sPESI ≥1 （14.28%）. And it was 4.07% in low-risk group with BUN ≤21.5 mg/dL and sPESI ≤2， which was near that of the group with sPESI =0 （3.85%）. ConclusionsBUN can help define a higher risk group with sPESI in APE admitted to ICU， which can contribute to the clinical management.