Objective:To observe the anti-inflammatory and glycometabolic effects of glutathione(GSH)on macrophages in collagen induced arthritis(CIA)mice.Methods:①CIA model establishment and groups:A total of 14 female DBA/1J mice were ran-domly divided into:CIA+PBS group and CIA+GSH group.The mice were sacrificed on the 50th day,collecting serum and isolating bone marrow derived macrophages(BMDM),which were marked as BMDM1.②Trained immunity model establishment and groups:BMDM were isolated from normal DBA/1J mice,and were pretreated with histone H3K27 demethylases inhibitor(GSKJ1)or PBS for 2 h.Then,serum from CIA model mice in vivo was incubated for 24 h,and the samples were grouped as follows:(CIA+GSH)+PBS group,(CIA+GSH)+GSKJ1 group,(CIA+PBS)+PBS group,(CIA+PBS)+GSKJ1 group.Lipopolysaccharide(LPS)was adopted to stimulated cells on the 6th day,which were marked as BMDM2.③RNA sequencing was used to detect differentially expressed genes(DEGs)and their function in BMDM1 and BMDM2.q-PCR was adopted to estimate the mRNA levels of PFK and Idh3g.The culture supernatants were used to measure the protein levels of TNF-α and IL-6 by ELISA.Results:①Compared with CIA+PBS group,the mice in CIA+GSH group showed lighter of joint swelling(P<0.05),less arthritis index(P<0.05),HE staining suggested less inflam-matory cell infiltration,Safranin O-fast green staining showed more chondrocytes,TRAP staining indicated reduced osteoclasts.②In BMDM1,GO analysis showed that DEGs were mainly involved in glutathione derivative metabolic process,IL-6 production,inflammatory response,innate immune response,regulation of primary metabolic process and glycolipid binding,compared with CIA+GSH and CIA+PBS group.In CIA+GSH group,the mRNA level of PFK was significantly decreased(P<0.05),while Idh3g was also significantly up-regulated(P<0.05),and the expression of TNF-α,IL-6 were both reduced(P<0.05)compared with CIA+PBS group.③In BMDM2,GO analysis showed that DEGs were also involved in inflammatory response,activation of innate immune response,regulation of tumor necrosis factor production,positive regulation of IL-6 production,regulation of glycolytic process and 1,3-β-D-glucan binding between CIA+GSH and CIA+PBS group.Furthermore,in(CIA+GSH)+PBS group,PFK was decreased(P<0.05),Idh3g was up-regulated(P<0.05),and IL-6 was also significantly down-regulated(P<0.05)compared with(CIA+PBS)+PBS group.However,there was no significant difference in the expression of Idh3g and PFK,moreover,TNF-α and IL-6 were significantly up-regulated compared with(CIA+GSH)+GSKJ1 group and(CIA+GSH)+PBS group.Conclusion:GSH can regulate glycometabolism and inflammatory response of macrophages via demethylation of histone H3K27,and it can also alleviate CIA in mice.

Objective:This study aimed to share preliminary experiences of single-incision plus two ports laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF).Methods:Following the 6th edition of the Japanese Gastric Cancer Treatment Guidelines, proximal gastrectomy with lymphadenectomy was performed. Using a single-port approach, the esophagus was transected at least 2 cm above the tumor's upper margin with linear staplers. The stomach was then extracted through a periumbilical incision, and the proximal stomach was subsequently transected extracorporeally, while ensuring appropriate resection margins on both the greater and lesser curvatures. A single flap was created before returning the remnant stomach to the abdominal cavity and re-establishing pneumoperitoneum. The No.2 clip was used to grasp and elevate the esophageal stump. An incision was made at the right lower edge of the esophageal stump to guarantee that the esophageal lumen was open. The linear stapler was then inserted into the openings of the stomach and esophagus to perform a side overlap anastomosis with a length of 3 cm. Another barbed suture was used to close the common opening of the esophagus and the stomach, and the same barbed suture were used to suture the gastric wall to the lower edge of the muscle flap. The first barbed suture was then used to sequentially suture the proximal brim of the flap to the esophagus and the right brim of the flap to the right brim of the mucosal window. After completion of anastomosis, a drainage tube was inserted through the right upper port. This procedure was employed from November 2023 to March 2024 on five patients diagnosed with adenocarcinoma of the esophagogastric junction and upper stomach. The cohort consisted of three males and two females, with an age range of 62 to 75 years and a body mass index (BMI) of 13.7 to 24.2 kg/m2. All cases were preoperatively staged as T1-2N0M0, confirmed by endoscopic biopsy and enhanced CT scans of the chest, abdomen, and pelvis.Results:All five patients successfully underwent the surgery. The median surgery time was 180-325 minutes, with the intraoperative blood loss of 30-50 ml. The number of lymph nodes harvested ranged from 18 to 27. The time to first flatus, and restore liquid diet and was 2.0-5.0 and 1.0-3.0 days, respectively. The postoperative length of stay was 9.0-11.0 days. The pain scores on the Numeric Rating Scale (NRS). On the first day, the pain scores were 3.0 in two cases, 2.0 in two cases, and 1.0 in one case. On the second day, the pain scores were 2.0 in two cases and 1.0 in three cases. On the third day, the pain scores were 1.0 in four cases and 2.0 in one case. No short-term postoperative complications were observed, and there were no perioperative deaths.Conclusion:Single-incision plus two ports laparoscopic proximal gastrectomy with ROSF is safe and feasible.

Objective:This study aimed to share preliminary experiences of single-incision plus two ports laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF).Methods:Following the 6th edition of the Japanese Gastric Cancer Treatment Guidelines, proximal gastrectomy with lymphadenectomy was performed. Using a single-port approach, the esophagus was transected at least 2 cm above the tumor's upper margin with linear staplers. The stomach was then extracted through a periumbilical incision, and the proximal stomach was subsequently transected extracorporeally, while ensuring appropriate resection margins on both the greater and lesser curvatures. A single flap was created before returning the remnant stomach to the abdominal cavity and re-establishing pneumoperitoneum. The No.2 clip was used to grasp and elevate the esophageal stump. An incision was made at the right lower edge of the esophageal stump to guarantee that the esophageal lumen was open. The linear stapler was then inserted into the openings of the stomach and esophagus to perform a side overlap anastomosis with a length of 3 cm. Another barbed suture was used to close the common opening of the esophagus and the stomach, and the same barbed suture were used to suture the gastric wall to the lower edge of the muscle flap. The first barbed suture was then used to sequentially suture the proximal brim of the flap to the esophagus and the right brim of the flap to the right brim of the mucosal window. After completion of anastomosis, a drainage tube was inserted through the right upper port. This procedure was employed from November 2023 to March 2024 on five patients diagnosed with adenocarcinoma of the esophagogastric junction and upper stomach. The cohort consisted of three males and two females, with an age range of 62 to 75 years and a body mass index (BMI) of 13.7 to 24.2 kg/m2. All cases were preoperatively staged as T1-2N0M0, confirmed by endoscopic biopsy and enhanced CT scans of the chest, abdomen, and pelvis.Results:All five patients successfully underwent the surgery. The median surgery time was 180-325 minutes, with the intraoperative blood loss of 30-50 ml. The number of lymph nodes harvested ranged from 18 to 27. The time to first flatus, and restore liquid diet and was 2.0-5.0 and 1.0-3.0 days, respectively. The postoperative length of stay was 9.0-11.0 days. The pain scores on the Numeric Rating Scale (NRS). On the first day, the pain scores were 3.0 in two cases, 2.0 in two cases, and 1.0 in one case. On the second day, the pain scores were 2.0 in two cases and 1.0 in three cases. On the third day, the pain scores were 1.0 in four cases and 2.0 in one case. No short-term postoperative complications were observed, and there were no perioperative deaths.Conclusion:Single-incision plus two ports laparoscopic proximal gastrectomy with ROSF is safe and feasible.

At present,implant restoration has become a hot research topic in the field of prosthodontics.The in-depth studies of new materials and new technologies enable immediate implantation,immediate and early loading to be realized,which meets the needs of patients for shortening the course of implant restoration and obtaining better aesthetic effects.However,compared with the traditional delayed implantation technology,it is equally challenging for clinicians how to achieve and even improve the initial and long-term stability of implants in order to raise the success rate of implant restoration.The initial stability of the implant is influenced by a combination of factors,including the implant,the patient's condition,and the surgical procedure.Recently,there have been a lot of studies on the influencing factors and common research methods for immediate implant stability and bone healing.Summarizing and analyzing them can provide reference for preoperative evaluation,surgical plan and loading timing of immediate implant restoration in the later stage.

Objective : To explore the role and molecular mechanism of circHIPK3 in the migration and invasion of nasopharyngeal carcinoma cells. Methods : Firstly , we searched public databases and analyzed the expression level of circHIPK3 in nasopharyngeal carcinoma tissues and non⁃cancerous tissues in Gene Expression Database (GEO) . Then , the circHIPK3 siRNA was synthesized and transfected into the NPC cell line 5 ⁃8F. After validate the efficiency of circHIPK3 knockdown , the proliferation , migration and invasion capacities of 5 ⁃8F cells were evaluated by CCK⁃8 , wound healing and transwell assay. Meanwhile , the mRNA and protein expression of downstream genes , including CDH1 , CDH2 , MMP2 , MMP9 and IL⁃6/STAT3 were determined by RT⁃qPCR and Western blot. Finally , transcriptome sequencing technology was used to analyze the significantly differentially expressed genes after the interference of circHIPK3 ⁃siRNA in 5 ⁃8F cells , in order to find out the key genes mediating the oncogenesis role of circHIPK3. Results : circHIPK3 expression significantly increased in nasopharyngeal carcinoma tissues compared with non⁃cancerous tissues ( P < 0. 05 ) . After siRNA⁃specific knockdown of circHIPK3 expression in 5 ⁃8F cells , the proliferation , scratch healing rate , and the number of migrated /invaded cells were significantly reduced (P < 0. 05 , P < 0. 01 , P < 0. 05 respectively) . Meanwhile , the mRNA and protein levels of CDH1 significantly increased (P < 0. 001) , but the CDH2 , MMP2 , MMP9 , IL⁃6/STAT3 mRNA and protein levels were significantly reduced (P < 0. 05) . Further analysis by RNA⁃seq showed that the expression of AL645922. 1 , SCO2 , AL136295. 1 and ISY1 ⁃RAB43 was significantly up⁃regulated( P < 0. 05 ) , and the expression of BIVM⁃ERCC5 , FAM47E⁃ST⁃BD1 , INO80B⁃WBP1 , NAIP , C15orf38⁃AP3S2 , BCL2L2⁃PABPN1 and SMIM11B was significantly down⁃regulated (P < 0. 05) in circHIPK3 ⁃siRNA transfected 5 ⁃8F cells. Conclusion circHIPK3 expression is significantly upregulated in nasopharyngeal carcinoma tissues. circHIPK3 promotes 5 ⁃8F cells proliferation , migration and invasion by regulating the expression of E ⁃Cadherin , N ⁃Cadherin , MMP2 , MMP9 and IL⁃6/STAT3. Genes such as AL645922.1 and BIVM⁃ERCC5 may play a key role in promoting the migration and invasion of nasopharyngeal carcinoma 5 ⁃8F cells mediated by circHIPK3.

The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca's area cluster,Wernicke's area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding clus-ter or BA.The findings of the present study could provide explanations for the functional connec-tions between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These pro-teomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.

Objective:To investigate the clinical characteristics and prognosis of the patients with nocardiosis.Methods:From January 2013 to July 2019, 44 patients with nocardiosis in Department of Infectious Diseases, Huashan Hospital, Fudan University in Shanghai were enrolled, and their clinical data were retrospectively analyzed, including baseline characteristics, clinical manifestations, underlying diseases history of glucocorticoid therapy, laboratory data (blood routine examination, procalcitonin, C-reactive protein, lymphocytes subsets, etc.), imaging changes, bacterial strain identification, treatment regimens and outcomes. According to the locations of infection, patients were divided into pulmonary nocardiosis, extrapulmonary single-organ nocardiosis and disseminated nocardiosis. The Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis H test was used for comparison among multiple groups. Results:Among the 44 cases of nocardiosis, 14 cases were pulmonary nocardiosis, 17 cases were extrapulmonary single-organ nocardiosis (including nine cases with central nervous system infection, six cases with skin and soft tissue infection, one case with abdominal abscess and one case with urinary tract infection) and 13 cases were disseminated nocardiosis (including four cases with bloodstream infection, six cases with central nervous system and lung or skin and soft tissue infection, three cases of lung and skin and soft tissue infection). Thirty-four cases had underlying diseases, and 27 cases received glucocorticoid or immunosuppressant treatment. The main symptom of 11 patients in pulmonary nocardiosis group was productive cough, while that of the patients in other two groups was fever. Nocardia species were mainly Nocardia brasiliensis, Nocardia nova and Nocardia farcinicaia. The white blood cell counts and neutrophils proportion were normal or slightly increased in 42 cases, and the platelets were normal or slightly decreased in 41 cases. Erythrocyte sedimentation rate increased in 19 cases, procalcitonin increased in 21 cases, C-reactive protein increased in 34 cases, and ferritin increased in 18 cases. A total of 34 patients were tested for lymphocyte subsets, of which 15 had CD4 + T lymphocytes decreased, 14 had CD8 + T lymphocytes increased, seven had B lymphocytes increased, seven had B lymphocytes decreased, and eight had natural killer cells decreased. The hemoglobin of patients with pulmonary nocardiosis was higher than that of patients with extrapulmonary infection, and the difference was statistically significant ( U=0.095, P=0.025). The imaging manifestations were mainly abscess and inflammatory exudation. Forty cases were cured or improved, one case was still on treatment, and three cases died. Conclusions:The clinical manifestations of nocardiosis involving various organs are non-specific. Standardized treatment could reduce the mortality of nocardiosis.

Objective To investigate the association between leukoaraiosis (LA) and early neurological deterioration (END) in patients with acute ischemic stroke.Methods Clinical data of 328 patients with acute ischemic stroke admitted in the hospital from January 2013 to January 2016 were retrospectively reviewed.According to the changes of National Institute of Health Stroke Scale (NIHSS) scores within 72 h after admission,88 patients (26.8%) were identified as END.Clinical manifestations,laboratory tests and radiographic findings were compared between END group and non-END group.ResultsUnivariate analysis indicated that age [(74.6±11.0) vs.(70.7±11.8) years,t=2.67,P=0.01],female sex [51.1% (45/ 88) vs.38.8%(93/240),χ2=4.05,P=0.04],initial NIHSS [M(Q1,Q3) 6(3,9) vs.3 (2,6),χ2=-4.38,P=0.00],systolic blood pressure [(155±28) vs.(149±20) mmHg(1 mmHg=0.133 kPa),t=2.04,P=0.04],responsible artery occlusion [18.2% (16/88) vs.8.3%(20/240),χ2=6.39,P=0.01],white cell count [(7.8±2.7) 109 vs.(7.1±2.2) 109,t=2.32,P=0.02],fasting blood glucose [(7.2±2.6) vs.(6.6±2.4) mmol/L,t=2.00,P<0.05] and C-reactive protein level [(24.5±27.1) vs.(14.6±23.2) g/L,t=3.25,P=0.00] were significantly different between END group and non-END group.After adjustment of confounding factors,LA in periventricular with Fazekas grade 2 (OR=2.309,95%CI: 1.070-4.984,P=0.03) and Fazekas grade 3 (OR=2.861,95%CI: 1.214-6.742,P=0.02) and LA in centrum semiovale with Fazekas grade 3 (OR=3.047,95%CI: 1.244-7.461,P=0.02) were independently associated with END.Conclusion Leukoaraiosis in periventricular group and centrum semiovale are associated with early neurological deterioration in patients with acute ischemic stroke.

ObjectiveTo observe the increasing effect of infrared irradiation on tyrosinase activity and melanin content in cultured normal human epidermal melanocytes in vitro and to explore the optimal dose of infrared irradiation.MethodsEpidermal melanocytes were isolated from normal human foreskin tissue,and subjected to primary culture.Methyl thiazolyl tetrazolium(MTT) assay was performed to evaluate the effect of different doses(0,20,60,80,100,140,240,320 J/cm2)of infrared light on the proliferation of melanocytes and to select the optimal irradiation dose.Then,melanocytes were irradiated with infrared light at the optimal dose for 3 consecutive days followed by the determination of tyrosinase activity,melanin content,and cell cycle via dopa oxidation assay,NaOH solubilization method and flow cytometry,respectively.ResultsThe best intervention dose of infrared light was 80 J/cm2.The tyrosinase activity(A492 nm) and melanin content(A492 nm)were 0.3601 ± 0.0301 and 0.2748 ± 0.0243 respectively in melanocytes after irradiation with infrared light of 80 J/cm2 for 3 days,significantly higher than those in unirradiated melanocytes(0.3114 ± 0.0341,0.2325 ±0.0254,respectively,both P ＜ 0.05),with an increase rate of 15.64％ and 18.19％ respectively.Cell cycle analysis revealed a decline in cell percentage in G1 phase(P ＜ 0.01 ) but a concomitant increase in cell percentage in G2 and S phase (both P ＜ 0.05) in irradiated melanocytes compared with unirradiated melanocytes.ConclusionsThe optimal dose of infrared light is 80 J/cm2 for the irradiation of melanocytes,and this dose of infrared light can increase melanin content,tyrosinase activity,differentiation and proliferation of melanocytes.

ObjectiveTo explore the effects of heat treatment and ultraviolet B (UVB) radiation alone or in combination on the expression of heat shock protein (HSP) 72 in human epidermal melanocytes.Methods Melanocytes were obtained from human foreskin,and subjected to primary culture.After 3 to 5 passages,the melanocytes were classified into 4 groups:control group (receiving no treatment),heat treatment group (treated with heat at 42 ℃ for 1 hour every day for 3 days),UVB group(irradiated with UVB at 50 mJ/cm2 daily for 3days),combination group(treated with heat at 42 ℃ for 1 hour followed by irradiation with UVB at 50 mJ/cm2daily for 3 days).After another 2- to 6-hour culture following the last treatment,melanocytes were collected and subjected to real time PCR and Western blot for the detection of HSP72 mRNA and protein expression,respectively.ResultsThe mRNA and protein expressions of HSP72 were significantly higher in the heat treatment group and combination group than in the control group (mRNA:6.584 ± 0.871 and 7.269 ± 0.454 vs.0.975 ± 0.089,both P ＜ 0.001; protein:2.022 ± 0.058 and 2.080 ± 0.045 vs.0.532 ± 0.033,both P ＜ 0.001 ),but was similar between the UVB group and control group (mRNA:0.832 ± 0.084 vs.0.975 ± 0.089,P ＞ 0.05;protein:0.546±0.021 vs.0.532 ± 0.033,P ＞ 0.05).The ANOVA of factorial design showed that neither heat treatment nor UVB irradiation had interaction effect on the mRNA or protein expression of HSP72 (F =2.106,1.399 respectively,both P ＜ 0.05).ConclusionsHeat treatment can cause an increase in the expression of HSP72,which may enhance the function of melanocytes and protect melanocytes from UVB induced damage.