ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective:To explore the incidence of sudden deafness accompanied with tinnitus, the selection of examination protocols and treatment, and to provide reference for the establishment of new guidelines for sudden deafness.Methods:CiteSpace software was used for analysis and data mining to analyze and summarize the computer-retrieved articles on diagnostic examination and treatment of sudden deafness accompanied with tinnitus collected from CNIC, Wanfang and Web of Science databases from 2011 to 2021.Results:A total of 207 randomized controlled studies were retrieved in this study, including 121 in Chinese and 86 in English. Finally, 74 Chinese literatures and 16 English literatures were included. Among the 74 valid Chinese literatures, 64 (86.5%) were accompanied with tinnitus, 58 (78.4%) with dizziness/vertigo, 25 (33.8%) with aural fullness, 10 (13.5%) with headache, 4 (5.4%) with insomnia, 4 (5.4%) with a mixture of dizziness and tinnitus, and 2 (2.7%) with vomiting. Among the 16 English literatures, 15 (93.8%) were accompanied with tinnitus, 12 (75.0%) with vertigo, 1 (6.3%) with aural fullness, and 1 (6.3%) with a mixture of various symptoms. Among the 64 Chinese articles mentioning tinnitus, only 9 mentioned tinnitus matching tests, and 1 mentioned that the treatment for tinnitus accompanying symptoms was sound therapy and psychological counseling. The incidence rates of tinnitus accompanying four different types of sudden deafness, from low to high, are as follows: low-to-mid frequency, 82.4%; mid-to-high frequency, 90.7%; complete deafness, 92.4%; and flat type, 92.8%.Conclusion:Tinnitus is the most common accompanying symptom of sudden deafness, and tinnitus matching test is an effective evaluation method. When establishing a scientific, comprehensive, and systematic diagnosis and treatment system or guidelines for sudden deafness, attention should be paid to the diagnosis and treatment of tinnitus symptoms and their adverse psychological reactions, in order to reduce the incidence of tinnitus patients in the later stage of recovery from sudden deafness.

Gastrointestinal tumors have been widely concerned because of increasing morbidity and mortality. In the process of exploring the therapeutic patterns of gastrointestinal tumors, patients treated with neoadjuvant therapies have good effect of tumor regression and favorable prognosis. Thus, neoadjuvant therapy strategies are recommended by major guidelines of gastrointestinal tumors in the world. Meanwhile, they have a great impact on the traditional methods of surgery, the influence mainly involves the reduction of the surgical margin and the scope of lymph node dissection in gastric cancer, while involves performing organ preservation and watch & wait in selective patients with colorectal cancer. These effects and changes were based on effective control of local recurrence by neoadjuvant therapies, and the advantages of neoadjuvant therapy in terms of tumor regression and survival supported by many studies. It is also based on the patient's desire for organ preservation and non-surgical treatment. Meanwhile, application of neoadjuvant therapy strategies increase surgical difficulty and postoperative complications, but the overall impact on patient prognosis is weak. Therefore, the selection of an appropriate treatment model after neoadjuvant therapy requires an effective overall post-treatment evaluation. In particular, it is necessary to pay attention to the evaluation of imaging, endoscopy, etc., while effectively performing monitoring and follow-up, and finally establishing an appropriate salvage treatment. This article will review the status and problems of individualized treatment after neoadjuvant therapy of gastrointestinal tumor.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Gastrointestinal tumors have been widely concerned because of increasing morbidity and mortality. In the process of exploring the therapeutic patterns of gastrointestinal tumors, patients treated with neoadjuvant therapies have good effect of tumor regression and favorable prognosis. Thus, neoadjuvant therapy strategies are recommended by major guidelines of gastrointestinal tumors in the world. Meanwhile, they have a great impact on the traditional methods of surgery, the influence mainly involves the reduction of the surgical margin and the scope of lymph node dissection in gastric cancer, while involves performing organ preservation and watch & wait in selective patients with colorectal cancer. These effects and changes were based on effective control of local recurrence by neoadjuvant therapies, and the advantages of neoadjuvant therapy in terms of tumor regression and survival supported by many studies. It is also based on the patient's desire for organ preservation and non-surgical treatment. Meanwhile, application of neoadjuvant therapy strategies increase surgical difficulty and postoperative complications, but the overall impact on patient prognosis is weak. Therefore, the selection of an appropriate treatment model after neoadjuvant therapy requires an effective overall post-treatment evaluation. In particular, it is necessary to pay attention to the evaluation of imaging, endoscopy, etc., while effectively performing monitoring and follow-up, and finally establishing an appropriate salvage treatment. This article will review the status and problems of individualized treatment after neoadjuvant therapy of gastrointestinal tumor.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Laparoscopic right hemicolectomy is currently the most commonly used surgical procedure for right-sided colon cancer. Although this procedure is maturing in terms of key tech-niques such as the extent of surgical resection, the extent of lymph node dissection, and the recons-truction of digestive tract, it still lacks a standardized surgical procedure and quality control system. In the pre-preparation phase of the COLOR Ⅳ study (an international, multicenter, randomized contro-lled trail comparing the efficacy of intracorporeal anastomosis versus extracorporeal anasto-mosis in laparoscopic right hemicolectomy for right-sided colon cancer), the research team of the authors formulates a standardized procedure for laparoscopic right hemicolectomy based on the Delphi survey, and develops a competency assessment tool for surgical ability and quality. Attempts are being made to automate the evaluation of surgical techniques using artificial intelligence. It is hoped that the above work will help colorectal surgeons to standardize surgical operations and reduce complications, provide support for the homogenization of multicenter clinical studies, and promote the implementation of structured training for this procedure.

Objective:To investigate the prevalence and associated factors of diabetic retinopathy (DR) among diabetic residents in Longyan of Fujian Province.Methods:A investigative research. From January 2022 to December 2023, a total of 10 061 diabetic patients enrolled in the chronic disease follow-up management system from 112 towns and sub-districts in 7 counties and districts of Longyan of Fujian Province were selected as the target population. A questionnaire survey, routine physical examination, vision test, and non-mydriatic fundus photography were conducted. A total of 762 cases with missing height, weight, blood pressure, fasting plasma glucose (FPG), and diabetes duration, and 507 cases with unclear fundus photography were excluded, resulting in 8 792 cases included in the final statistical analysis. DR diagnosis and classification were based on the 2019 International Clinical Classification of DR. The prevalence of DR was calculated for single-eye or double-eye DR cases as 1 case; the more severe eye was used for DR grading in double-eye DR cases. Statistical analysis was performed by grouping based on the presence or absence of DR and dividing into age groups ≤67 years and >67 years. χ2 test was used to analyze factors associated with prevalence; binary multivariate logistic regression analysis was employed to identify influencing factors of DR. Results:Among the 8 792 cases, 888 (10.1%, 888/8 792) were diagnosed with DR (DR group), and 7 904 (89.9%, 7 904/8 792) had no DR (non-DR group). Compared to the non-DR group, the DR group showed significant increases in FPG ( Z=-12.448), diabetes duration ( Z=-18.936), systolic blood pressure ( Z=-4.237), diastolic blood pressure ( Z=-2.881), and body mass index (BMI) ≥24 kg/m 2 ( P<0.001). Significant differences were also found between the two groups in hypertension ( χ2=11.450), hyperlipidemia ( χ2=5.100), kidney disease ( χ2=7.039), family history of diabetes ( χ2=5.025), and regular medication use ( χ2=66.034) ( P<0.05). There were 4 688 cases in the ≤67 years group and 4 104 in the >67 years group. In the ≤67 years group, significant differences in DR prevalence were found for FPG levels ( χ2=111.754), diabetes duration ( χ2=231.658), BMI ( χ2=12.404), systolic blood pressure ( χ2=17.912), regular medication use ( χ2=40.727), hyperlipidemia ( χ2=6.816), and hypertension history ( χ2=6.775) ( P<0.05). In the >67 years group, significant differences in DR prevalence were found for FPG levels ( χ2=59.916), diabetes duration ( χ2=128.362), systolic blood pressure ( χ2=5.183), regular medication use ( χ2=22.097), kidney disease ( χ2=6.251), and family history of diabetes duration ( χ2=4.967) ( P<0.05). No significant differences in DR prevalence were found based on sex, education level, smoking history, alcohol consumption, exercise habits, heart disease history, or other family disease history ( P>0.05). Logistics regression analysis results show that patients aged >67 years, FPG [odds ratio (OR)=1.074, 95%confidence interval ( CI) 1.046-1.102], diabetes duration ( OR=1.088, 95% CI 1.071-1.106), systolic blood pressure ( OR=1.007, 95% CI 1.001-1.013), and kidney disease ( OR=3.617, 95% CI 1.268-10.320) were identified as risk factors for DR ( P<0.05). In patients aged ≤67 years, FPG ( OR=1.088, 95% CI 1.067-1.110), diabetes duration ( OR=1.108, 95% CI 1.091-1.125), and systolic blood pressure ( OR=1.008, 95% CI 1.003-1.013) were identified as independent risk factors for DR ( P<0.05), while BMI ≥24 kg/m 2 ( OR=0.934, 95% CI 0.908-0.965) was a protective factor for DR ( P<0.05). Age, regular medication use, hypertension, and hyperlipidemia were identified as potential confounding factors for DR occurrence. Conclusions:The prevalence of DR among diabetes patients in Longyan of Fujian Province, is 10.1%. FPG, diabete duration, and systolic blood pressure are independent risk factors for DR, while age, regular medication use, hypertension, and hyperlipidemia are potential confounding factors for DR occurrence.

ObjectiveTo evaluate the efficacy of Geriatric Nutritional Risk Index (GNRI) on admission on predicting neurological outcomes for stroke patients at the convalescence stage (three months after stroke). MethodsA total of 277 inpatients with ischemic stroke in Wenzhou TCM Hospital of Zhejiang Chinese Medical University from November, 2022 to January, 2023 were divided into good outcome group (n = 195) and poor outcome group (n = 82) according to the score of modified Rankin Scale (mRS) three months after stroke. Their clinical data and GNRI were compared. ResultsCompared with the good outcome group, the poor outcome group showed a lower level of GNRI (t = -9.569, P < 0.001), more proportion of patients with high nutritional risk (χ² = 68.861, P < 0.001). More cases with poor outcome were found with higher nutritional risk (Z = 65.406, P < 0.001). After covariate adjustment, higher level of GNRI was an independent protective factor for poor outcome three months after stroke (OR = 0.895, 95%CI 0.864 to 0.927, P < 0.05), and the OR increased with the nutritional risk grade of GNRI (P < 0.05). The area under the curve (AUC) of GNRI, score of NIHSS, and BMI were 0.812 (Z = 11.576, P < 0.001), 0.759 (Z = 8.328, P < 0.001), and 0.594 (Z = 2.716, P = 0.007), respectively; while the combination of GNRI and NIHSS was more effective (AUC = 0.875, Z = 17.389, P < 0.001). The sensitivities of GNRI, NIHSS and the combination of the two in predicting neurological function were 65.85%, 76.83% and 79.21%, respectively, and the specificities were 81.54%, 60.51% and 82.95%, respectively. ConclusionGNRI on admission is associated with neurological function three months after stroke. GNRI can be used alone or in combination with NIHSS score to predict neurological outcome in the rehabilitation period, which is a useful complement to traditional predictors.

Objective:To investigate the effect of obstruction on the prognosis and possible mechanisms in colorectal cancer patients.Methods:Among 1574 cases of colorectal cancer who were treated in Beijing Friendship Hospital, Capital Medical University from January 2003 to December. 2014, 194 cases had preoperative intestinal obstruction. Firstly, described the clinical characteristics of 194 patients with obstruction, then COX multivariate regression analysis was performed on the 1574 colorectal cancer cohort to confirm whether the preoperative obstruction was independent predictor for the overall survival. Finally, propensity score matching method was used to match obstruction and non-obstruction cases, then compared overall survival difference.Results:In 194 cases of obstructive colorectal cancer, 60.3% and 37.1% of the tumors were located in the left and right respectively. The 55.7% of the patients had tumors larger than 5 cm in diameter, the median survival time was 39.7 months (95% CI: 28.3-60.4). Multivariate COX analysis, after adjusted for related confounding factors, found that preoperative obstruction is still an independent risk factor for poor prognosis ( HR=1.41, 95% CI: 1.01-1.97). After propensity score matching, 140 and 560 patients were included in the obstructive group and the non-obstructive group. The two groups were more balanced in most baseline characteristics. The median survival time of the two groups was 42.4 and 116.3 months ( P<0.001), the overall survival of obstructive patients was significantly worse than that of non-obstructive patients. Conclusions:Preoperative obstruction is an independent risk factor for poor prognosis of colorectal cancer. This may be due to the difficulty of surgery and low radical cure rate for obstructive colorectal cancer.