A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

In recent years, with the improvement of people's awareness of physical examination and the more accurate detection equipment, the detection rate of pulmonary nodules is getting higher and higher. Surgical resection is the first choice for the treatment of malignant pulmonary nodules, but multiple pulmonary nodules, nodules in complex areas and those with surgical contraindications are not suitable for surgery. As an effective, less invasive and low-cost treatment, ablation has developed rapidly in the treatment of multiple pulmonary nodules. This article introduces the progress of several common ablation techniques (radiofrequency ablation, microwave ablation, cryoablation) in the treatment of multiple pulmonary nodules, the indications and contraindications of ablation techniques, the efficacy evaluation and complications after ablation therapy, and the prospects of ablation techniques in the treatment of multiple pulmonary nodules.

Functional disorders of the Golgi apparatus are harmful to the health of organisms, leading to various diseases. Removing damaged Golgi apparatus is crucial for maintaining cellular homeostasis, therefore, autophagy of Golgi apparatus has gradually attracted attention. This article summarizes Golgi autophagy, briefly describes its structure and functions, Golgi autophagy receptors, and the role of Golgi autophagy in disease treatment. It also proposes the new concept of Golgimedicine, which looks forward to the role of Golgi in disease diagnosis, treatment, prognosis, genetic diseases, and rare diseases. This article aims to explore the scientific connotations of Golgi autophagy, Golgi structure and function from the perspective of Golgimedicine, providing theoretical references for drug target research, new drug development, and the healthy development of humanity.

Objective To investigate the distribution characteristics of pathogens in adult community-acquired pneumonia(CAP)patients who visited the fever clinic before and after the outbreak of the novel coronavirus infection,and to provide theoretical basis for the diagnosis,treatment,and prevention of CAP.Methods CAP patients who visited the fever clinic of Peking University Third Hospital from June 2017 to July 2022 were included in the study and divided into pre-outbreak and post-outbreak groups based on the time point(January 24,2020,when Beijing entered the first-level COVID-19 prevention and control).Respiratory samples were collected and pathogen nucleic acid detection was performed using real-time fluorescence quantitative polymerase chain reaction.The detection and distribution of pathogens were analyzed.Results A total of 415 CAP patients were included,divided into pre-outbreak group(312 cases)and post-outbreak group(103 cases).Mycoplasma pneumoniae,Streptococcus pneumoniae,and Influenza A virus were the three most common pathogens in the pre-outbreak CAP group.In the post-outbreak community-acquired pneumonia,Influenza B virus,Klebsiella pneumoniae and Streptococcus pneumoniae were the three most common pathogens.The incidence of Influenza A virus,Parainflluenza virus,and Mycoplasma pneumoniae was significantly higher in the pre-outbreak period than in the post-outbreak period,and the differences between the two groups were statistically significant(all P＜0.05).Conclusion Before and after the epidemic,viral infection are the main pathogens of CAP patients,which is of great significance for future empirical treatment,protection of susceptible population and control of infectious diseases.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the effects of medullary differentiation-2(MD-2)in obesity-induced myocardial injury by regulating adenosine 5'-monophosphate-activated protein kinase(AMPK)activity.Methods The obese mice model was established by feeding high-fat feed.The wild-type and MD-2 gene knockout mice were randomly divided into wild-type(WT)-control group(fed normally),WT-model group(fed with high-fat diet),knockout(KO)-control group(fed normally)and KO-model group(fed with high-fat diet)with 8 mice in each group.At week 16,creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)were measured by reagent kits;the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured with ultrasonic apparatus;the pathological changes in myocardial tissue were observed by hematoxylin and eosin(HE)staining and Masson staining;the protein expression of phosphorylation AMPK(p-AMPK)was measured by Western blot.Results HE staining and Masson staining results revealed significant necrosis and fibrosis of the myocardial tissue in WT-model group,while the degrees of necrosis and fibrosis in KO-model group were significantly reduced.The LVEF values of the WT-control group,WT-model group,KO-control group and KO-model group were(83.98±7.58)％,(52.03±4.91)％,(76.42±3.89)％and(73.71±4.22)％,respectively;the LVFS values of each group were(53.61±8.51)％,(24.56±3.76)％,(48.14±5.00)％and(44.07±3.74)％,respectively;the CK-MB values of each group were(49.83±15.49),(83.75±11.90),(54.03±18.66)and(66.85±12.98)U·L-1,respectively;the LDH values of each group were(12.24±3.20),(27.90±6.10),(13.55±3.55)and(15.53±2.58)U·L-1,respectively;the relative expression levels of p-AMPK in each group were 221.31±88.76,46.29±10.07,148.66±32.02 and 161.49±78.11.Compared with WT-control group,the above indicators in WT-model group,compared with WT-model group,the above indicators in KO-model group,the differences were statistically significant(all P＜0.05).Conclusion MD-2 mediates high-fat feed induced myocardial injury in obese mice by inhibiting AMPK activity.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.