Objective:To explore the value of intraoperative multimodal monitoring in superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery in evaluating hemodynamic parameters and blood-brain barrier disruption, as well as their correlations with postoperative perfusion changes.Methods:A retrospective case series study was performed; 60 patients with ischemic cerebrovascular diseases admitted to Department of Neurosurgery, Lianyungang Clinical Medical College of Nanjing Medical University (Lianyungang First People's Hospital) from March 2023 to October 2024 were selected, including 17 patients with moyamoya disease and 43 patients with chronic internal carotid artery occlusion and/or chronic symptomatic MCA stenosis/occlusion. All patients were confirmed by CTA or DSA and underwent STA-MCA M4 segment bypass surgery. Intraoperatively, microvascular Doppler ultrasound (MDU), sodium fluorescein angiography, and indocyanine green angiography combined with Flow800 (ICG-Flow800) were used to monitor the blood-brain barrier disruption grade, as well as the peak systolic velocity (PSV) and blood flow direction of the STA and recipient artery before and after arterial anastomosis. Cerebral blood perfusion improvement was reexamined by CT perfusion (CTP) 7 days and 1 month after surgery. These 60 patients were divided into a group with blood flow into the sylvian fissure (inflow group, n=27) and a group with blood flow out of the sylvian fissure (outflow group, n=33) according to the direction of recipient artery blood flow before arterial anastomosis, and further subdivided into subgroups with PSV≤10 cm/s and >10 cm/s based on the recipient artery PSV. Clinical and imaging data of these patients were collected and analyzed as follows: (1) CTP parameters such as cerebral blood volume, cerebral blood flow, mean transit time, and time to peak before surgery, 7 days after surgery, and 1 month after surgery were compared; (2) differences between the recipient artery PSV before arterial anastomosis and recipient artery exiting sylvian fissure velocity (RA.EXV) or recipient artery entering sylvian fissure velocity (RA.ESV) of the recipient artery after anastomosis were compared; (3) differences in ICG-Flow800 fluorescence intensity curve parameters such as delay time, rise time, curve slope, time to peak, and maximum fluorescence intensity of the cerebral surface veins before and after arterial anastomosis were compared; (4) spearman rank correlation was used to analyze the correlation of recipient artery PSV before arterial anastomosis with preoperative CTP parameters in all patients, the correlations of RA.ESV in the inflow group or RA.EXV in the outflow group with CTP parameters 7 days after surgery, and the correlations of blood-brain barrier disruption grade with preoperative CTP parameters, recipient artery PSV before arterial anastomosis, and RA.ESV or RA.EXV after arterial anastomosis in all patients. Results:(1) The blood flow direction of all recipient arteries became bidirectional after surgery. Cerebral blood perfusion improved to varying degrees after surgery: the mean transit time 7 days and 1 month after surgery, and cerebral blood flow 1 month after surgery were significantly higher compared with those before surgery ( P<0.05). (2) Regardless of the blood flow direction (into or out of the sylvian fissure), the RA.ESV or RA.EXV after anastomosis was significantly higher than the recipient artery PSV before anastomosis when the recipient artery PSV≤10 cm/s ( P<0.05). (3) For all patients, the ICG-Flow800 fluorescent intensity curve parameters of cerebral surface veins after anastomosis improved significantly compared with that before anastomosis ( P<0.05). (4) Preoperative recipient artery PSV was positively correlated with preoperative CBF in all patients ( rs=0.445, P=0.020). In the inflow group, postoperative RA.ESV was positively correlated with Tmax 7 days after surgery ( rs=0.490, P=0.009). The blood-brain barrier disruption grade was positively correlated with preoperative Tmax in all patients ( rs=0.478, P=0.012). Conclusion:Intraoperative multimodal monitoring in STA-MCA bypass surgery can provide surgeons with detailed hemodynamic parameters and blood-brain barrier disruption data, enabling real-time evaluation of surgical outcomes to optimize operative decision-making.

Objective:To evaluate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on cognitive function, cerebral perfusion, and integrity of white matter tracts by comparing cognitive function scores, fractional anisotropy (FA), time to maximum (T max), and cerebral blood flow (CBF) at different time points before and after STA-MCA bypass, and analyze the relations of cognitive function with cerebral perfusion and white matter tract integrity so as to provide evidences for treatment of moyamoya disease (MMD) patients with mild cognitive impairment. Methods:A retrospective analysis was performed; 30 MMD patients with mild cognitive impairment received STA-MCA bypass at Department of Neurosurgery, Lianyungang Hospital Affiliated to Xuzhou Medical University (Lianyungang First People's Hospital) from January 2023 to August 2024 were enrolled. Before and 1, 3, and 6 months after STA-MCA bypass, all patients accepted Montreal cognitive assessment (MoCA), CT perfusion imaging, and diffusion tensor imaging (DTI). Differences in MoCA score, CBF, T max, and FA at different time points before and after surgery were compared. Spearman rank correlation was used to analyze the correlation of MoCA score with cerebral perfusion parameters and FA. Results:(1) In these MMD patients with mild cognitive impairment, CBF 3 and 6 months after STA-MCA bypass was significantly increased compared with that before STA-MCA bypass, and CBF 6 months after STA-MCA bypass was significantly higher than that 1 and 3 months after STA-MCA bypass ( P<0.05); T max 1, 3 and 6 months after STA-MCA bypass was significantly shortened compared with that before STA-MCA bypass, and T max 6 months after STA-MCA bypass was significantly shortened than that 1 and 3 months after STA-MCA bypass ( P<0.05); FA 6 months after STA-MCA bypass was significantly increased compared with that before, and 1 and 3 months after STA-MCA bypass ( P<0.05); MoCA score 6 months after STA-MCA bypass was significantly increased compared with that before and 1 month after STA-MCA bypass ( P<0.05). (2) In MMD patients with mild cognitive impairment, the preoperative MoCA score was positively correlated with preoperative CBF and FA ( r s=0.428, P=0.018; r s=0.438, P=0.015) and negatively correlated with preoperative T max ( r s=-0.380, P=0.039); 6 months after STA-MCA bypass, the MoCA score was positively correlated with CBF and FA ( r s=0.365, P=0.047; r s=0.400, P=0.028) and negatively correlated with T max ( r s=-0.371, P=0.043). Conclusion:STA-MCA bypass can improve cerebral perfusion, white matter fiber tract repair and cognitive function in MMD patients with mild cognitive impairment, and improvement of cognitive function is related to cerebral perfusion and white matter fiber tract repair.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

Objective:To explore the value of intraoperative multimodal monitoring in superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery in evaluating hemodynamic parameters and blood-brain barrier disruption, as well as their correlations with postoperative perfusion changes.Methods:A retrospective case series study was performed; 60 patients with ischemic cerebrovascular diseases admitted to Department of Neurosurgery, Lianyungang Clinical Medical College of Nanjing Medical University (Lianyungang First People's Hospital) from March 2023 to October 2024 were selected, including 17 patients with moyamoya disease and 43 patients with chronic internal carotid artery occlusion and/or chronic symptomatic MCA stenosis/occlusion. All patients were confirmed by CTA or DSA and underwent STA-MCA M4 segment bypass surgery. Intraoperatively, microvascular Doppler ultrasound (MDU), sodium fluorescein angiography, and indocyanine green angiography combined with Flow800 (ICG-Flow800) were used to monitor the blood-brain barrier disruption grade, as well as the peak systolic velocity (PSV) and blood flow direction of the STA and recipient artery before and after arterial anastomosis. Cerebral blood perfusion improvement was reexamined by CT perfusion (CTP) 7 days and 1 month after surgery. These 60 patients were divided into a group with blood flow into the sylvian fissure (inflow group, n=27) and a group with blood flow out of the sylvian fissure (outflow group, n=33) according to the direction of recipient artery blood flow before arterial anastomosis, and further subdivided into subgroups with PSV≤10 cm/s and >10 cm/s based on the recipient artery PSV. Clinical and imaging data of these patients were collected and analyzed as follows: (1) CTP parameters such as cerebral blood volume, cerebral blood flow, mean transit time, and time to peak before surgery, 7 days after surgery, and 1 month after surgery were compared; (2) differences between the recipient artery PSV before arterial anastomosis and recipient artery exiting sylvian fissure velocity (RA.EXV) or recipient artery entering sylvian fissure velocity (RA.ESV) of the recipient artery after anastomosis were compared; (3) differences in ICG-Flow800 fluorescence intensity curve parameters such as delay time, rise time, curve slope, time to peak, and maximum fluorescence intensity of the cerebral surface veins before and after arterial anastomosis were compared; (4) spearman rank correlation was used to analyze the correlation of recipient artery PSV before arterial anastomosis with preoperative CTP parameters in all patients, the correlations of RA.ESV in the inflow group or RA.EXV in the outflow group with CTP parameters 7 days after surgery, and the correlations of blood-brain barrier disruption grade with preoperative CTP parameters, recipient artery PSV before arterial anastomosis, and RA.ESV or RA.EXV after arterial anastomosis in all patients. Results:(1) The blood flow direction of all recipient arteries became bidirectional after surgery. Cerebral blood perfusion improved to varying degrees after surgery: the mean transit time 7 days and 1 month after surgery, and cerebral blood flow 1 month after surgery were significantly higher compared with those before surgery ( P<0.05). (2) Regardless of the blood flow direction (into or out of the sylvian fissure), the RA.ESV or RA.EXV after anastomosis was significantly higher than the recipient artery PSV before anastomosis when the recipient artery PSV≤10 cm/s ( P<0.05). (3) For all patients, the ICG-Flow800 fluorescent intensity curve parameters of cerebral surface veins after anastomosis improved significantly compared with that before anastomosis ( P<0.05). (4) Preoperative recipient artery PSV was positively correlated with preoperative CBF in all patients ( rs=0.445, P=0.020). In the inflow group, postoperative RA.ESV was positively correlated with Tmax 7 days after surgery ( rs=0.490, P=0.009). The blood-brain barrier disruption grade was positively correlated with preoperative Tmax in all patients ( rs=0.478, P=0.012). Conclusion:Intraoperative multimodal monitoring in STA-MCA bypass surgery can provide surgeons with detailed hemodynamic parameters and blood-brain barrier disruption data, enabling real-time evaluation of surgical outcomes to optimize operative decision-making.

Objective:To evaluate the effect of superficial temporal artery to middle cerebral artery (STA-MCA) bypass on cognitive function, cerebral perfusion, and integrity of white matter tracts by comparing cognitive function scores, fractional anisotropy (FA), time to maximum (T max), and cerebral blood flow (CBF) at different time points before and after STA-MCA bypass, and analyze the relations of cognitive function with cerebral perfusion and white matter tract integrity so as to provide evidences for treatment of moyamoya disease (MMD) patients with mild cognitive impairment. Methods:A retrospective analysis was performed; 30 MMD patients with mild cognitive impairment received STA-MCA bypass at Department of Neurosurgery, Lianyungang Hospital Affiliated to Xuzhou Medical University (Lianyungang First People's Hospital) from January 2023 to August 2024 were enrolled. Before and 1, 3, and 6 months after STA-MCA bypass, all patients accepted Montreal cognitive assessment (MoCA), CT perfusion imaging, and diffusion tensor imaging (DTI). Differences in MoCA score, CBF, T max, and FA at different time points before and after surgery were compared. Spearman rank correlation was used to analyze the correlation of MoCA score with cerebral perfusion parameters and FA. Results:(1) In these MMD patients with mild cognitive impairment, CBF 3 and 6 months after STA-MCA bypass was significantly increased compared with that before STA-MCA bypass, and CBF 6 months after STA-MCA bypass was significantly higher than that 1 and 3 months after STA-MCA bypass ( P<0.05); T max 1, 3 and 6 months after STA-MCA bypass was significantly shortened compared with that before STA-MCA bypass, and T max 6 months after STA-MCA bypass was significantly shortened than that 1 and 3 months after STA-MCA bypass ( P<0.05); FA 6 months after STA-MCA bypass was significantly increased compared with that before, and 1 and 3 months after STA-MCA bypass ( P<0.05); MoCA score 6 months after STA-MCA bypass was significantly increased compared with that before and 1 month after STA-MCA bypass ( P<0.05). (2) In MMD patients with mild cognitive impairment, the preoperative MoCA score was positively correlated with preoperative CBF and FA ( r s=0.428, P=0.018; r s=0.438, P=0.015) and negatively correlated with preoperative T max ( r s=-0.380, P=0.039); 6 months after STA-MCA bypass, the MoCA score was positively correlated with CBF and FA ( r s=0.365, P=0.047; r s=0.400, P=0.028) and negatively correlated with T max ( r s=-0.371, P=0.043). Conclusion:STA-MCA bypass can improve cerebral perfusion, white matter fiber tract repair and cognitive function in MMD patients with mild cognitive impairment, and improvement of cognitive function is related to cerebral perfusion and white matter fiber tract repair.

Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.

Objective:To explore correlation between the distribution of TCM syndromes in patients with chronic heart failure (CHF) and its cardiopulmonary function.Methods:The general data and cardiopulmonary function test results of 220 hospitalized patients with CHF in the Cardiology Department of Shaanxi Provincial Hospital of Traditional Chinese Medicine from June 2018 to June 2023 were retrospectively analyzed, and they were divided into 95 cases with deficiency in nature syndrome and 125 cases with excess in superficiality syndrome according to TCM syndrome diagnosis criteria. The difference of cardiopulmonary function indexes among patients with different TCM syndromes was observed, and the correlation between the distribution of TCM syndromes and cardiopulmonary function indexes was analyzed.Results:In 95 patients with deficiency in nature syndrome, qi-deficiency syndrome (21.82%, 48/220) accounted for the highest proportion, and in 125 patients with excess in superficiality, water-drinking syndrome (39.09%, 86/220) accounted for the highest proportion. Left ventricular ejection fraction (LVEF) [(48.84±5.14) % vs. (56.55±6.01) %, t=10.02], stroke cardiac output (SV) [(55.99±6.23) ml vs. (62.86±6.47) ml, t=7.93], cardiac output (CO) [(2.60±0.59) L/min vs. (2.99±0.51) L/min, t=5.25], cardiac index (CI) [(1.54±0.39) L/min?m 2vs. (1.82±0.42) L/min?m 2, t=5.05] of patients with deficiency in nature syndrome were lower than patients with excess in superficiality syndrome ( P<0.001). FVC [(2.16±0.37) L vs. (2.51±0.48) L, t=5.90], maximum vital capacity (VC max) [(2.66±0.42) L vs. (3.01±0.49) L, t=5.58], FEV1 [(2.73±0.42) L vs. (3.15±0.53) L, t=6.35] of patients with deficiency in nature syndrome were lower than those in patients with excess in superficiality syndrome ( P<0.001). Point-biserial correlation analysis showed that patients of CHF excess in superficiality syndrome were significantly correlated with LVEF, SV, CO, CI, FVC, VC max, and FEV1 ( r values are 0.698, 0.705, 0.684, 0.675, 0.719, 0.742, and 0.640, respectively, P<0.05). Conclusions:The deficiency in nature syndrome of CHF patients is qi-deficiency syndrome, and the excess in superficiality syndrome is water-drinking syndrome. The cardiopulmonary function of patients with excess in superficiality syndrome is at a lower level, and there is a significant correlation between patients with excess in superficiality syndrome and cardiopulmonary function. It can provide reference for TCM syndrome diagnosis of CHF patients by monitoring cardiopulmonary function.

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.