Objective:To investigate the effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in NAFLD mice.Methods:Totally 60 mice were divided into a normal group of 10 mice and a high-fat diet group of 50 mice. The high-fat diet group was given a high-fat diet to establish a NAFLD mouse model. The high-fat feed group was divided into model group, metformin group, and Xiaomudan Granules low-, medium-, and high-dosage groups according to the random number table method. Xiaomudan Granules low-, medium-, and high-dosage groups were orally administered with concentrated Xiaomudan Granules at dosages of 11.7, 23.4, and 46.8 g/kg, respectively. The metformin group was orally administered with metformin solution at a dose of 0.2 g/kg, while the normal group and model group were orally administered with distilled water of equal volume once a day for 8 consecutive weeks. The liver oil red O staining of mice was observed in each group. The protein expressions of p-PERK, p-eIF2α, ATF4, C/EBP homologous protein (CHOP), CCAAT enhancer binding protein alpha (C/EBPα), C/EBPβ, and steroid regulatory element binding protein 2 (SREBP2) were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of ATF4, CHOP, C/EBPα, C/EBPβ, and SREBP2.Results:The liver tissue structure and steatosis of mice were improved in Xiaomudan Granules groups. Compared with the model group, the expressions of p-PERK/PERK, ATF4, C/EBPα, C/EBPβ, and SREBP2 proteins decreased in Xiaomudan Granules groups and the metformin group ( P<0.01 or P<0.05). The expressions of p-eIF2α/eIF2α and CHOP proteins decreased in the Xiaomudan Granules medium- and high-dosage groups and the metformin group ( P<0.01); compared with the model group, the levels of ATF4, CHOP, C/EBPα, and C/EBPβ mRNA in Xiaomudan Granules groups and the metformin group decreased ( P<0.01), while the levels of SREBP2 mRNA in the Xiaomudan Granules medium- and high-dosage groups and the metformin group decreased ( P<0.01). Conclusion:Xiaomudan Granules may improve liver lipid metabolism and reduce liver fat deposition in NAFLD mice by regulating the PERK/eIF2α/ATF4 pathway.

Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway. Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with de-pression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The effi-cacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assess-ments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hema-toxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the ex-pression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological ef-fects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Ex-cept for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were ob-served using HE staining,Nissl staining,TUNEL staining,and transmission electron mi-croscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed. Results(i)ZJJF significantly reduced the high blood glucose,insulin,and glycated he-moglobin levels in model rats(P<0.01).It increased autonomous activity and decreased de-spair-like behaviors(P<0.01),improved the pathological damage of hippocampal neurons,increased the number of neuronal nuclei(P<0.01),and reduced the number of mechanocytes,vacuolar cells,and apoptotic neurons(P<0.05,P<0.01,and P<0.01,respec-tively).ZJJF down-regulated the expression levels of pro-apoptotic proteins Bax and caspase-3(P<0.01),up-regulated the anti-apoptotic protein Bcl-2(P<0.01),and significantly inhibit-ed the overexpression of phosphorylated JNK(p-JNK),Elk-1,and c-fos(P<0.01).(ii)SP6 in-creased autonomous activity and reduced despair time in model rats(P<0.05),although it had no significant effects on sucrose preference(P>0.05).It increased the number of Nissl bodies in hippocampal neurons(P<0.01),reduced the protein expression levels of Bax(P<0.01)and caspase-3(P<0.05),and decreased the number of apoptotic neurons(P<0.05).SP6 also increased the expression level of Bcl-2(P<0.01),and inhibited the high expression levels of p-JNK,Elk-1,and c-fos(P<0.01,P<0.01,and P<0.05,respectively),suggesting that hip-pocampal neuronal apoptosis in diabetic rats with depression is associated with abnormal ac-tivation of JNK signaling pathway.Compared with ZJJF group,ZJJF+Aniso group showed a decrease in sucrose preference(P<0.05)and an increase in despair time(P<0.01)with more notable hippocampal neuronal damage.This group also exhibited a decrease in expression level(P<0.01)Bcl-2 and an increase in expression levels of Bax,caspase-3,p-JNK,Elk-1,and c-fos(P<0.01,P<0.05,P<0.05,P<0.01,and P<0.05,respectively),indicating that the antidepressant effects of ZJJF,its improvement of neuronal apoptosis,and regulation of JNK signaling molecules could all be reversed by a specific JNK agonist. Conclusion ZJJF exerts a significant hypoglycemic effect and ameliorates the apoptosis of hippocampal neurons by inhibiting the activation of JNK signaling pathway,which is a promising formula for the treatment of diabetic depression in clinical settings.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To explore the association between childhood growing environment and depressive symptoms in young old persons aged 60 to 74 years.Methods:The data of the fourth wave of China Health and Re-tirement Longitudinal Study in 2018 and the life course survey in 2014 were used to secondary analysis.A total of 7 642 young old persons aged 60 to 74 years were included,and the 10-item of the Center for Epidemiological Stud-ies Depression(CES-D-10)scale was used to evaluate the depressive symptoms.The generalized linear mixed effects model was used to explore the relationship between childhood growing environment and depressive symp-toms in the young old persons.Results:The detection rate of depressive symptoms occurrence in the young old per-sons was 37.2％.The risk factors of depressive symptoms included female(OR=1.89),rural(OR=1.35),hav-ing hunger experience(OR=1.22),poor relationship with male dependents(OR=1.72),female caregiver's expe-riences of being bedridden due to illness(OR=1.38),community insecurity(OR=1.59),more harmonious neigh-borhood relationship(OR=1.20)and less harmonious neighborhood relationship(OR=1.81).The protective fac-tors of depressive symptoms occurrence included moderate(OR=0.79)and high(OR=0.50)per capita house-hold income,and educated father(OR=0.84)(P＜0.05).Conclusion:Childhood growing environment is an influ-ential factor of depressive symptoms in the young old persons.The long-term health effects of childhood environ-ment should be paid attention to.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

ObjectiveTo compare the incidence of adverse events following immunization （AEFI） between vaccination with 13-valent pneumococcal polysaccharide conjugate vaccine （PCV13） alone and with other vaccines at the same time. MethodsWe obtained PCV13 vaccination adverse reaction reports for children vaccinated in Shanghai between 2017‒2021 from the National Immunization Program Information Management System and collected the information and the data of children vaccinated with PCV13 from The Shanghai vaccination information system. We compared the incidence of adverse reactions between stand-alone and simultaneous vaccination. ResultsA total of 11 175 PCV13 AEFI cases after stand-alone vaccination and 215 PCV13 AEFI cases after simultaneous vaccination were reported during 2017‒2021 in Shanghai， and the incidence rates were 1 252.34/10⁵ and 1 455.75/10⁵， respectively. ORV was the one mostly vaccinated with PCV13 at the same time， and the AEFI incidence was 1 706.67/10⁵. The most reported symptom was fever after PCV13 vaccination， no matter by stand-alone and simultaneous vaccination with the respective incidence rates of 876.69/10⁵ and 1 442.21/10⁵. ConclusionIn general， PCV13 vaccinated with other vaccines at the same time slightly increases the incidence of AEFI.

Stroke has become the leading cause of death in China, and carotid atherosclerosis is an important risk factor for ischemic stroke. In current carotid atherosclerosis diagnosis and treatment guidelines, patients are stratified based on the degree of vascular stenosis. However, the presence of carotid atherosclerotic vulnerable plaques can cause ischemic stroke at any time, regardless of the degree of carotid stenosis. The development of MRI technology, especially the advent of high-resolution MRI, enables non-invasive assessment of carotid plaque structure and properties, and provides optimized treatment strategies for high-risk stroke population in the early stage to achieve the goal of prevention and treatment of stroke.

Objective:To analyze the long-term therapeutic effect of endoscopic submucosal dissection (ESD) on the treatment of early gastric cancer (EGC).Methods:We retrospectively reviewed EGC patients who underwent ESD at Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), from January 2009 to December 2016. The incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were analyzed. Kaplan-Meier method was used to analyze 5-years recurrence free survival (RFS) and 5-years disease special survival (DSS) of all patients.Results:A total of 255 EGC patients were enrolled in this study, included 175 differentiated early gastric cancer (D-EGC) patients and 80 undifferentiated early gastric cancer (UD-EGC) patients. Among them, 171 patients within the extended indication of ESD while 84 patients beyond the extended indication of ESD. Among the 225 patients, the incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were 2.0%, 2.0% and 2.4%, respectively. The local recurrence rates of D-EGC group and UD-EGC group was 1.7% and 2.5%, respectively, without significant difference ( χ2=0.176, P=0.675). The incidence rates of synchronous and heterogenous cancer in the D-EGC group were 2.3% and 3.4%, higher than 1.2% and 0 of UD-EGC group, although there was no significant difference ( χ2=0.306, P=0.580 vs χ2=2.809, P=0.094). There were no significant differences in 5-years RFS (91.3% vs 95.9%, P=0.236) and 5-years DSS (100% vs 98.6%, P=0.156) between D-EGC group and UD-EGC group. Conclusions:The long-term outcome of ESD in the treatment of EGS is good. More attention should be paid to the occurrence of local recurrence and heterogeneous cancer in EGC patients undergo ESD. These patients still have a good long-tern outcome even undergoing ESD for more than once.

Objective:To analysis the clinical and follow-up data of the early colorectal carcinoma (ECC) after endoscopic resection, and explore the long-term outcome of patients who underwent the endoscopic resection.Methods:During June 2008 to June 2016, data of endoscopic resection for 550 cases of ECC were collected, including general information and follow-up data. The influence factors of disease-free survival rate of ECC after endoscopic resection were analyzed and the risk factors on long-term outcomes such as submucosa invasion depth, poorly differentiated adenocarcinoma, vascular invasion and positive vertical margin were investigated.Results:The mean follow-up time of 550 patients treated with endoscopy was (60.7±36.8) months. Among them, 433 cases were high-level intra-mucosal neoplasia, 117 cases were submucosa invasion carcinoma (the invasion depth <1 000 μm were 33 cases, ≥1 000 μm were 84 cases), 461 cases were curative resection, while 89 cases were non-curative resection. During the follow-up, 6 patients occurred recurrence or metastasis, including 2 patients with local recurrence (1 patient accompanied by lymph node metastasis) and 4 patients with lymph node metastasis (2 patients accompanied by distant metastasis). The overall 5-years disease-free survival rate was 98.8%, the 5-years disease-free survival rate was 100.0% for patients with curative resection and 93.3% for patients with non-curative resection. A total of 89 cases underwent non-curative resection were accompanied with invasion depth ≥1 000 μm, vascular invasion, poorly differentiated adenocarcinoma and positive vertical margin. Among them, 62 cases were accompanied with 1 risk factor, 23 cases with 2 risk factors and 4 cases with 3 risk factors. The risks of lymph nodes and distant metastasis raised with the increase of risk factors.Conclusions:The incidence of lymph node metastasis in ECC is extremely low. Endoscopic treatment can achieve a good long-term outcome. Close follow-up should be conducted after endoscopic treatment, and additional treatment should be selected reasonably for the early colorectal carcinoma after endoscopic non-curative resection to improve the therapeutic efficacy of endoscopic resection.