Background and Aims:Gastroesophageal reflux disease(GERD)is a common complication following sleeve gastrectomy(SG),particularly in patients with concomitant hiatal hernia,where symptoms tend to be more persistent and refractory,significantly impairing postoperative quality of life.This study aimed to evaluate the efficacy of laparoscopic hiatal hernia repair combined with gastroesophageal fixation in SG patients with severe GERD and hiatal hernia,providing clinical reference for revisional surgical strategies.Methods:The clinical data of 9 patients with severe GERD after SG who underwent laparoscopic hiatal hernia repair and gastroesophageal fixation at Huashan Hospital,Fudan University,between January 2023 and June 2024 were retrospectively analyzed.GerdQ scores,proportion of endoscopically confirmed reflux esophagitis,and proton pump inhibitor(PPI)usage were compared before and after surgery.Surgical parameters and follow-up outcomes were also recorded.Results:All patients successfully completed the surgery without major intraoperative complications,and the mean postoperative hospital stay was 5.22 d.After a mean follow-up period of 15.27 months,the GerdQ score significantly decreased from 11.67±2.00 to 7.22±1.48.The proportion of patients with GerdQ score≥8 decreased from 100.00％to 44.44％,and the rate of endoscopically confirmed GERD dropped from 88.89％to 11.11％;PPI use also significantly declined,with all differences reaching statistical significance(all P＜0.05).Conclusion:Laparoscopic hiatal hernia repair combined with gastroesophageal fixation can effectively alleviate reflux symptoms in SG patients with coexisting hiatal hernia,demonstrating favorable short-term efficacy and high safety.This approach may be a preferable surgical option for selected patients.

Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective To explore the effect of the preservation of infrapatellar fat pad on pain,incision healing and function recovery in patients with knee osteoarthritis after joint replacement.Methods The clinical data of 127 patients with knee osteoarthritis who underwent joint replacement in the hospital from June 2019 to September 2022 were retrospectively collected.According to the preservation of infrapatellar fat pad,the subjects were divided into a control group(removing infrapatellar fat pad,67 cases)and an observation group(preserving infrapatellar fat pad,60 cases).The changes in length of patellar tendon,pain,knee function and range of motion were analyzed.The occurrence of adverse reactions was statistically analyzed.Results At 12 months after surgery,the length of patellar tendon was reduced.The length of patellar tendon in observation group[(38.8±6.24)mm]was longer than that in control group[(36.2±6.71)mm](P＜0.05).Observation group of patellar tendon length rate is lower than the control group[(4.1±1.18)％vs(10.7±3.01)％],there was statistical significance between the two groups(P＜0.05).Pain in both groups was alleviated at 1 month,3 months,6 months and 12 months after surgery.The changes in observation group were greater than those in control group(P＜0.05).During follow-up,the incidence of adverse reactions in observation group(6.67％)was lower than that in control group(14.93％)(P＞0.05).The range of motion and function of knee joint were improved at 12 months after surgery,and the improvement in observation group was greater than that in control group(P＜0.05).Conclusion Preserving infrapatellar fat pad is more beneficial to relieving postoperative pain and restoring knee function in patients with knee osteoarthritis after joint replacement.Therefore,the intact infrapatellar fat pad should be preserved as possible in clinical practice.

Objective To explore the effect of the preservation of infrapatellar fat pad on pain,incision healing and function recovery in patients with knee osteoarthritis after joint replacement.Methods The clinical data of 127 patients with knee osteoarthritis who underwent joint replacement in the hospital from June 2019 to September 2022 were retrospectively collected.According to the preservation of infrapatellar fat pad,the subjects were divided into a control group(removing infrapatellar fat pad,67 cases)and an observation group(preserving infrapatellar fat pad,60 cases).The changes in length of patellar tendon,pain,knee function and range of motion were analyzed.The occurrence of adverse reactions was statistically analyzed.Results At 12 months after surgery,the length of patellar tendon was reduced.The length of patellar tendon in observation group[(38.8±6.24)mm]was longer than that in control group[(36.2±6.71)mm](P＜0.05).Observation group of patellar tendon length rate is lower than the control group[(4.1±1.18)％vs(10.7±3.01)％],there was statistical significance between the two groups(P＜0.05).Pain in both groups was alleviated at 1 month,3 months,6 months and 12 months after surgery.The changes in observation group were greater than those in control group(P＜0.05).During follow-up,the incidence of adverse reactions in observation group(6.67％)was lower than that in control group(14.93％)(P＞0.05).The range of motion and function of knee joint were improved at 12 months after surgery,and the improvement in observation group was greater than that in control group(P＜0.05).Conclusion Preserving infrapatellar fat pad is more beneficial to relieving postoperative pain and restoring knee function in patients with knee osteoarthritis after joint replacement.Therefore,the intact infrapatellar fat pad should be preserved as possible in clinical practice.

Background and Aims:Gastroesophageal reflux disease(GERD)is a common complication following sleeve gastrectomy(SG),particularly in patients with concomitant hiatal hernia,where symptoms tend to be more persistent and refractory,significantly impairing postoperative quality of life.This study aimed to evaluate the efficacy of laparoscopic hiatal hernia repair combined with gastroesophageal fixation in SG patients with severe GERD and hiatal hernia,providing clinical reference for revisional surgical strategies.Methods:The clinical data of 9 patients with severe GERD after SG who underwent laparoscopic hiatal hernia repair and gastroesophageal fixation at Huashan Hospital,Fudan University,between January 2023 and June 2024 were retrospectively analyzed.GerdQ scores,proportion of endoscopically confirmed reflux esophagitis,and proton pump inhibitor(PPI)usage were compared before and after surgery.Surgical parameters and follow-up outcomes were also recorded.Results:All patients successfully completed the surgery without major intraoperative complications,and the mean postoperative hospital stay was 5.22 d.After a mean follow-up period of 15.27 months,the GerdQ score significantly decreased from 11.67±2.00 to 7.22±1.48.The proportion of patients with GerdQ score≥8 decreased from 100.00％to 44.44％,and the rate of endoscopically confirmed GERD dropped from 88.89％to 11.11％;PPI use also significantly declined,with all differences reaching statistical significance(all P＜0.05).Conclusion:Laparoscopic hiatal hernia repair combined with gastroesophageal fixation can effectively alleviate reflux symptoms in SG patients with coexisting hiatal hernia,demonstrating favorable short-term efficacy and high safety.This approach may be a preferable surgical option for selected patients.

Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective:To analyze the correlation between blood pressure variability (BPV) and behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD).Methods:In this retrospective cohort study, sixty-nine patients with AD from Beijing Tiantan Hospital, Capital Medical University, the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease were consecutively collected from February 1 to August 31, 2023. The patients were divided into the BPSD group (50 patients) and the control group (19 patients) according to with or without BPSD. The patients′ general information were collected, such as age at enrolment, gender, duration of education, and history of hypertension, diabetes, cerebral infarction, hyperlipoidemia, smoking, alcohol consumption, and carrier status of apolipoprotein E epsilon4 allele (APOE ε4). The 24-hour ambulatory blood pressure monitoring instruments were also used to collect the patients′ mean systolic blood pressure, mean diastolic blood pressure and 12 BPV indicators, which covered standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure throughout the day, daytime and nighttime. The Montreal Cognitive Assessment (MoCA) was used to assess their cognitive function, and the Activity of Daily Living (ADL)-14 items was used to assess their daily living abilities; hypothesis tests were used to compare the general information, MoCA scores, ADL-14 items scores, mean blood pressure and BPV indicators between the two groups; the multivariate logistic regression analysis was conducted to explore the related factors of BPSD in AD patients; Spearman correlation analysis was used to test the correlation between the total score of neuropsychiatric inventory (NPI) and BPV indicators in AD patients with BPSD.Results:In the BPSD group, the incidence rate of hypertension and MoCA scores were both significantly lower than those in the control group [44.00% vs 73.70%, (9.72±5.60) vs (14.53±5.52) points], but ADL-14 items scores and nocturnal systolic blood pressure CV were both significantly higher [23.00 (17.00, 29.25) vs 14.00 (14.00, 17.00) points, 8.89%±2.26% vs 7.52%±2.30%] (all P<0.05). Elevated ADL-14 items scores ( OR=1.379, 95% CI: 1.131-1.681) and nocturnal systolic blood pressure CV ( OR=1.387, 95% CI: 1.003-1.918) were positive correlation factors for the risk of BPSD in AD patients (all P<0.05). The daytime systolic blood pressure SD ( r=0.375) and CV ( r=0.357) were both positively correlated with total NPI scores in AD patients with BPSD (all P<0.05). Conclusion:BPV is correlated with BPSD in AD patients. Nocturnal systolic blood pressure CV is a positive correlation factor for the risk of BPSD in AD patients, and the total scores of NPI in AD patients are positively correlated with daytime systolic blood pressure SD and CV. It suggests that controlling BPV is a potential therapeutic measure to improve the BPSD of AD patients.

Background and purpose:Hepatocellular carcinoma(HCC)is a major disease seriously threatening human health.Poly(ADP-ribose)polymerase-1(PARP1)is an enzyme that catalyzes poly ADP-ribosylation.Given the role of PARP1 in DNA damage repair,it is generally considered as an oncogene.However,the expression of PARP1 and its mechanism in HCC are not yet clear.This study aimed to investigate the role of PARP1 in the occurrence and development of HCC and its potential mechanisms.Methods:First,we analyzed the expression pattern of PARP1 in The Cancer Genome Atlas(TCGA)and Clinical Proteomic Tumor Analysis Consortium(CPTAC)HCC database,and identified the expression trend of PARP1 in our HCC cohort using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Then,the enzyme activity of PARP1 was inhibited by PJ34,an inhibitor of PARP1 and the expression of PARP1 in HCC cell lines was downregulated with small RNA interference technology.Based on these models,the following experiments were conducted:First,the effect of PARP1 on cell viability was assessed by cell counting kit-8(CCK-8)assay and flow cytometry;Second,the expression levels of stemness-related genes in HCC cells were identified using RTFQ-PCR;Third,the effect of inhibition of PARP1 on migration and invasion of HCC cells was detected by migration and invasion assay(transwell assay).Finally,bioinformatic analysis was performed to identify new target genes and the pathways regulated by PARP1 in HCC progression.Rescue experiments were performed to determine whether PARP1 target genes were involved in the malignant phenotypes of HCC cells.Results:The expression of PARP1 was significantly up-regulated in HCC tissues in both TCGA and CPTAC database.RTFQ-PCR and Western blot assays showed that PARP1 was obviously up-regulated in HCC tissues compared to paracancerous tissues.Survival analysis showed that PARP1 expression was significantly negatively correlated with the prognosis of patients.The results of CCK-8,flow cytometry,RTFQ-PCR and transwell assay indicated that inhibition of PARP1 attenuated proliferation and activity of HCC cells,as well as weakened their stemness,migration and invasion.Bioinformatics analysis suggested that PARP1-regulated genes were enriched in the nuclear factor-κB(NF-κB)and necroptosis pathways,with POU class homeobox 2(POU2F2)potentially being a target gene of PARP1.Correlation analysis,along with RTFQ-PCR and Western blot detection,confirmed that the expression of POU2F2 was regulated by PARP1,while not affected by PJ34,indicating the effect of nonenzymatic function of PARP1 on POU2F2.CCK-8,flow cytometry and RTFQ-PCR results showed that the reintroduction of POU2F2 enhanced proliferative capacity,increased activity,and promoted stemness of HCC cell lines with PARP1 knockdown.Conclusion:By positively regulating the expression of POU2F2,PARP1 promotes malignant phenotypes of HCC cells,providing new insights for clinical treatment and drug development for HCC.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.