AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)recep-tor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthe-sia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was ter-minated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anes-thesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tis-sues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloid β-protein(Aβ),and p-tau were detected by Western blot.RE-SULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points dur-ing anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+in-creased.The protein levels of GluN1 subunit,Aβ and p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves and δ waves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβ and p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLU-SION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power of δ EEG waves,but has no significant effect on recovery time.Me-mantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA recep-tors,Aβ and p-tau,and attenuating neuroinflammation.

AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)recep-tor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthe-sia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was ter-minated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anes-thesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tis-sues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloid β-protein(Aβ),and p-tau were detected by Western blot.RE-SULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points dur-ing anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+in-creased.The protein levels of GluN1 subunit,Aβ and p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves and δ waves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1β and TNF-α in the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβ and p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLU-SION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power of δ EEG waves,but has no significant effect on recovery time.Me-mantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA recep-tors,Aβ and p-tau,and attenuating neuroinflammation.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the correlation between sedentary behavior and exercise compliance in ileostomy patients for developing targeted exercise intervention.Methods:Patients undergoing laparoscopic low anterior rectal resection combined with prophylactic ileostomy from Aug 2018 to Aug 2023 were enrolled in this study by convenience sampling method. A survey was conducted at 3 months after surgery to investigate their sedentary behavior and exercise compliance.Results:The daily sedentary time of 144 patients was (7.94±1.76) h, and 63.8% (92/144) of patients had sedentary time ≥8 h/d. The exercise compliance score was 32.24±8.32 and the total adherence rate was 54.29%±13.85%. Sedentary behavior was inversely correlated with exercise rehabilitation compliance ( r=-0.222, P<0.05). Univariate analysis revealed that age, tumor stage, chronic medical history, NRS 2002 score, main caregiver, ostomy adaptability, frailty, previous exercise habits were important influencing factors of sedentary behavior (all P<0.05). Multivariate Logistic regression analysis indicated that stoma adaptability and exercise compliance, age, primary caregiver, and previous exercise habits were independent factors affecting postoperative sedentary behavior (all P<0.05). Combining the above factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.729-0.883), with an sensitivity and specificity of 72.8%, 80.8%, respectively. Conclusion:Exercise intervention in survivorship management is essential for enhancing the health-related quality of life in patients with ileostomy.

Objective:To investigate the correlation between sedentary behavior and exercise compliance in ileostomy patients for developing targeted exercise intervention.Methods:Patients undergoing laparoscopic low anterior rectal resection combined with prophylactic ileostomy from Aug 2018 to Aug 2023 were enrolled in this study by convenience sampling method. A survey was conducted at 3 months after surgery to investigate their sedentary behavior and exercise compliance.Results:The daily sedentary time of 144 patients was (7.94±1.76) h, and 63.8% (92/144) of patients had sedentary time ≥8 h/d. The exercise compliance score was 32.24±8.32 and the total adherence rate was 54.29%±13.85%. Sedentary behavior was inversely correlated with exercise rehabilitation compliance ( r=-0.222, P<0.05). Univariate analysis revealed that age, tumor stage, chronic medical history, NRS 2002 score, main caregiver, ostomy adaptability, frailty, previous exercise habits were important influencing factors of sedentary behavior (all P<0.05). Multivariate Logistic regression analysis indicated that stoma adaptability and exercise compliance, age, primary caregiver, and previous exercise habits were independent factors affecting postoperative sedentary behavior (all P<0.05). Combining the above factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.729-0.883), with an sensitivity and specificity of 72.8%, 80.8%, respectively. Conclusion:Exercise intervention in survivorship management is essential for enhancing the health-related quality of life in patients with ileostomy.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.
Aged ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Neurodegenerative Diseases ; Parkinson Disease/therapy*

OBJECTIVETo investigate the relationship of prognostic nutritional index (PNI) with clinicopathological factors and the clinical significance of PNI in predicting the survival in patients with advanced gastric cancer.

METHODSClinicopathological and follow-up data of 1150 patients with advanced gastric cancer who underwent radical gastrectomy from January 2007 to December 2010 at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital were analyzed retrospectively. The PNI value was calculated [PNI=absolute value of lymphocyte(10/L)×5 + serum albumin (g/L)] and was grouped according to the mean value of PNI. Relationships of PNI with gender, age, tumor size, depth of invasion, tumor differentiation, tumor stage, tumor location, lymph node metastasis and tumor marker detection level were analyzed. At the same time, for the survival analysis of patients, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis.

RESULTSOf 1150 cases, 846 were males and 304 were females with an average age of 62 (24 to 88) years. The average maximum diameter of tumor was 5.4(1.0 to 20.0) cm. Tumor of 159 cases located in the gastric fundus, 221 cases in the gastric body, 705 cases in the gastric antrum and 65 cases in the whole stomach. Well differentiated tumors were found in 198 cases and poorly differentiated tumors in 952 cases. As for depth of tumor invasion, 165 cases were T2, 343 cases were T3 and 642 cases were T4. According to TNM stage, 53 cases were stage I(, 397 cases were stage II( and 700 cases were stage III(. The average lymph node metastasis rate was 25.0%, meanwhile lymph node metastasis was N0 in 296 cases, N1 in 246 cases, N2 in 277 cases and N3 in 331 cases. Blood examination showed hemoglobin ≤130 g/L in 544 cases and >130 g/L in 606 cases; carcinoembryonic antigen ≤5 μg/L in 903 cases and >5 μg /L in 247 cases; carbohydrate antigen 19-9 ≤37 kU/L in 927 cases and >37 kU/L in 223 cases. In whole patients, the mean value of PNI was 51.81(24.5 to 80.4), PNI ≤51.81 group had 563 cases, and PNI >51.81 group had 587 cases. Between PNI ≤51.81 group and PNI >51.81 group, age (χ=22.661, P=0.000), tumor location (χ=8.979, P=0.030), tumor size (χ=34.509, P=0.000), tumor stage (χ=11.644, P=0.003), depth of tumor invasion (χ=21.681, P=0.000) and hemoglobin (χ=112.262, P=0.000) were significantly different. Patients were followed up for an average of 45.1 months (4 to 108). The 5-year survival rate was 37.7% in PNI ≤51.81 group, while it was 47.0% in PNI >51.81 group, whose difference was statistically significant (χ=8.326, P=0.004). Univariate analysis showed that patients with PNI ≤51.81(P=0.004), deeper tumor invasion (P=0.000), more metastatic lymph nodes (P=0.000), later TNM stage (P=0.000), lymph node metastasis rate >25.02%(P=0.000), hemoglobin ≤130 g/L(P=0.011), the maximum tumor diameter >5.4 cm (P=0.000), tumor undifferentiated (P=0.001), CEA >5 μg /L (P=0.000), CA199 >37 kU/L(P=0.000) and tumors locating in whole stomach (P=0.000) had poorer prognosis. Multivariate analysis showed that the age (HR=1.195, 95%CI: 1.019 to 1.401, P=0.028), the depth of tumor invasion(HR=1.429, 95%CI: 1.231 to 1.658, P=0.000), the number of metastatic lymph node (HR=1.536, 95%CI:1.330 to 1.774, P=0.000), the lymph node metastasis rate (HR=1.376, 95%CI:1.102 to 1.717, P=0.005), tumor TNM stage (HR=1.387, 95%CI: 1.026 to 1.876, P=0.033) and tumor size(HR=1.182, 95%CI: 1.005 to 1.390, P=0.043) were independent prognostic factors of gastric cancer patients, while PNI (HR=0.913, 95%CI: 0.774 to 1.076, P=0.278) was not an independent risk prognostic factor of gastric cancer patients.

CONCLUSIONSAlthough the PNI is not an independent risk factor of overall survival in patients with advanced gastric cancer, it is still an indicator of survival in patients with gastric cancer. Improving preoperative nutritional status in patients with gastric cancer may contribute to a better prognosis.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.

OBJECTIVETo investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL.

METHODSAccording to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients.

RESULTSmiR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P < 0.05).

CONCLUSIONSDown regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.

Biomarkers ; Carcinoma in Situ ; metabolism ; pathology ; Down-Regulation ; Humans ; Hyperplasia ; pathology ; Laryngeal Neoplasms ; metabolism ; pathology ; Larynx ; pathology ; MicroRNAs ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; RNA, Neoplasm ; metabolism ; Real-Time Polymerase Chain Reaction

Objective To investigate the expression of microRNA-10a-5p ( miR-10a) in laryngeal epithelial premalignant lesions ( LEPL ) and to analyze the correlations of its dys-regulation with clinicopathologic parameters of LEPL.Methods According to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ (CIS).The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction ( qRT-PCR) , and correlated with the clinical and follow-up data of all LEPL patients.Results miR-10a was down-regulated in LEPL with increasing grade of dysplasia.There was significantly statistical difference between low-risk ( MID+MOD) and high-risk ( SD+CIS) lesion groups ( P=0.03).The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P<0.05).Conclusions Down regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.