ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

Objective:This study evaluated the efficacy of the PST technique: Preservation of the left colic artery (P), suture reinforcement (S), and transanal tube (T) combined with selective fecal diversion via end ileostomy, in preventing anastomotic leakage following laparoscopic anterior resection (LAR) for mid-to-low rectal cancer.Methods:We retrospectively collected data for this descriptive case series from patients who underwent laparoscopic LAR with complete or partial application of the PST technique, some of whom received prophylactic ileostomy, at the Department of Colorectal Surgery, Zhongshan Hospital Affiliated to Fudan University, and its Xiamen Branch between July, 2022 and December, 2024. "Partial PST" was defined as the implementation of PS (Preservation of the left colic artery + suture reinforcement), PT (Preservation of the left colic artery + transanal tube), ST (suture reinforcement + transanal tube), or a single T procedure (Transanal tube). The primary outcome measures were the proportion of patients who received the PST technique and terminal ileostomy, as well as the incidence of anastomotic leaks.Results:Among 198 patients, 145 received complete PST. Fifty-three patients underwent partial PST (PT) because anastomotic reinforcement was not feasible due to an excessively low anastomosis or obesity. All patients achieved R0 resection. Postoperative pathology showed that 108 patients (54.5%) were at T3-T4 stage, and 81 patients (40.9%) had poorly differentiated adenocarcinoma or mucinous adenocarcinoma. A total of 19.7% (39/198) of patients developed grade II or higher postoperative complications, including 11 cases (5.6%) of surgical site infection and 7 cases (3.5%) of urinary retention. Five patients were rehospitalized within 30 days after surgery, among whom 2 had intestinal obstruction, and 3 developed grade C anastomotic leaks that required reoperation for salvage enterostomy. The overall incidence of anastomotic leakage was 3.0% (6/198). Fifty-three patients (26.8%) received protective ileostomy, with an anastomotic leak incidence of 1.9% (1/53). Methylene blue leakage occurred in 20 patients (10.1%), all of whom received prophylactic ileostomy and had no anastomotic leakage postoperatively. Among 61 patients who received neoadjuvant chemoradiotherapy before surgery, 28 underwent prophylactic ileostomy, and none developed anastomotic leaks after surgery.Conclusions:Routine application of the PST technique during laparoscopic low anterior resection, along with prophylactic enterostomy for ultra-high-risk populations, can effectively control the incidence of anastomotic leakage.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:This study evaluated the efficacy of the PST technique: Preservation of the left colic artery (P), suture reinforcement (S), and transanal tube (T) combined with selective fecal diversion via end ileostomy, in preventing anastomotic leakage following laparoscopic anterior resection (LAR) for mid-to-low rectal cancer.Methods:We retrospectively collected data for this descriptive case series from patients who underwent laparoscopic LAR with complete or partial application of the PST technique, some of whom received prophylactic ileostomy, at the Department of Colorectal Surgery, Zhongshan Hospital Affiliated to Fudan University, and its Xiamen Branch between July, 2022 and December, 2024. "Partial PST" was defined as the implementation of PS (Preservation of the left colic artery + suture reinforcement), PT (Preservation of the left colic artery + transanal tube), ST (suture reinforcement + transanal tube), or a single T procedure (Transanal tube). The primary outcome measures were the proportion of patients who received the PST technique and terminal ileostomy, as well as the incidence of anastomotic leaks.Results:Among 198 patients, 145 received complete PST. Fifty-three patients underwent partial PST (PT) because anastomotic reinforcement was not feasible due to an excessively low anastomosis or obesity. All patients achieved R0 resection. Postoperative pathology showed that 108 patients (54.5%) were at T3-T4 stage, and 81 patients (40.9%) had poorly differentiated adenocarcinoma or mucinous adenocarcinoma. A total of 19.7% (39/198) of patients developed grade II or higher postoperative complications, including 11 cases (5.6%) of surgical site infection and 7 cases (3.5%) of urinary retention. Five patients were rehospitalized within 30 days after surgery, among whom 2 had intestinal obstruction, and 3 developed grade C anastomotic leaks that required reoperation for salvage enterostomy. The overall incidence of anastomotic leakage was 3.0% (6/198). Fifty-three patients (26.8%) received protective ileostomy, with an anastomotic leak incidence of 1.9% (1/53). Methylene blue leakage occurred in 20 patients (10.1%), all of whom received prophylactic ileostomy and had no anastomotic leakage postoperatively. Among 61 patients who received neoadjuvant chemoradiotherapy before surgery, 28 underwent prophylactic ileostomy, and none developed anastomotic leaks after surgery.Conclusions:Routine application of the PST technique during laparoscopic low anterior resection, along with prophylactic enterostomy for ultra-high-risk populations, can effectively control the incidence of anastomotic leakage.

Diabetic macrovascular disease,as one of the most important complications of diabetes,seriously endangers the life and health of patients.The development of diabetic macrovascular disease is often irreversi-ble in the later stage,so timely and accurate diagnosis is very important.Taking appropriate examination methods according to different conditions is helpful to the early screening and prognosis monitoring of diabetic macrovascular disease,and reduce the economic and life burden of patients.

Objective: To investigate the curative effect of local application of CpG-oligodeoxynucleotide (CpG-ODN) combined with 4-1BB monoclonal antibody in hepatoma-bearing mice, and to evaluate the effect of 4-1BB monoclonal antibody on CpG-ODN immunotherapy. Methods: H22 single cell suspension was injected subcutaneously into the axilla and four limbs of the BALB/c male mice to establish a tumor-bearing mice model. After 7 days, 30 mice with corresponding tumor-bearing volume were screened and randomly divided into model control group, CpG group and CpG+4-1BB group, and the drug was injected into the tumors of left lower extremity. The same batch of normal mice was selected as normal control group. Survival of mice was recorded. Tumor-bearing volume and organ index were calculated. Serum levels of interleukin (IL) - 12 and interferon (IFN) gamma and spleen CD8⁺T lymphocyte ratio were measured. The measurement data were analyzed by analysis of variance. The survival rate of each group of mice was analyzed by log-rank test. Results: Mice in the model control group with tumor-bearing volume had a sustained growth before the execution. CpG group and the CpG+4-1BB group [(976.08 ± 29.55) mm³, (47.25 ± 0.93) mm³)] tumor-bearing volume was decreased than model group [(1 336.52 ± 39.40) mm3] (F = 5 329.273, P < 0.05). CpG+4-1BB group distant tumor-bearing volume [(611.83 ± 113.02) mm3] was decreased than model group and CpG group [(1 406.62 ± 51.09) mm³, (1 380.01 ± 51.44) mm3] (F = 247.160, P < 0.05), but there was no significant difference between the CpG group and the model group (P > 0.05). Serum IL-12 concentration (23.90 ± 2.33 pg/ml), IFN-γ concentration (103.02 ± 6.10 pg/ml) and spleen CD8⁺T cell ratio (4.54 ± 0.62%) in the model group were lower than those in the normal group (P < 0.05). Serum IL-12 concentration in CpG group and CpG+4-1BB group (29.21 ± 2.23 pg/ml, 37.04 ± 1.49 pg/ml), IFN-γ concentration (116.12 ± 4.08 pg/ml, 138.65 ± 1.72 pg/ml), CD8⁺T cell ratio (6.65 ± 0.64%, 12.73 ± 0.88%) were higher than the model group, while CpG+4-1BB group was higher than the CpG group (P < 0.05). The survival rate of CpG+4-1BB group was higher than that of model group and CpG group (χ² = 25.544, P < 0.05), but there was no significant difference between CpG group and model group (P > 0.05). There was no significant difference in organ index between the four groups (P > 0.05). Conclusion 4-1BB monoclonal antibody combined with CpG-ODN therapy can shrink hepatoma-bearing capacity, inhibit the growth of distant tumors and significantly prolong the survival time of mice.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Disease-Free Survival ; Drug Therapy ; methods ; Humans ; Lung ; drug effects ; radiation effects ; surgery ; Lung Neoplasms ; pathology ; surgery ; therapy ; Neoplasm Grading ; Neuroendocrine Tumors ; pathology ; surgery ; therapy ; Outcome Assessment (Health Care) ; Radiotherapy ; methods

Objective To explore the application value of endoscopic ultrasonography (EUS) in the diagnosis of suspected obstructive jaundice in acute biliary pancreatitis and its effect on treatment outcomes. Methods Clinical data were retrospectively collected in 96 patients with acute biliary pancreatitis (ABP) who were suspected obstructive jaundice. Patients were divided into early EUS scanning group (EES) and delay EUS scanning group (DES). Clinical treatment results and test results were compared between the two groups. Results The diagnosis sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EUS were 96.43 %, 82.5 %, 90.63 %, 88.52 % and 96.29 %. Early EUS scan with 72 h could identify the etiology of ABP and subsequent treatment based on the EUS can easily decrease the white blood cell count, percentage of neutrophils, total bilirubin and serum amylase (P < 0.05). The pain relief rate in EEI group after 1 week treatment was significantly higher than that in the DES group (87.50 % vs 66.67 %, P = 0.027) and average length of hospitalization was shorter [(12.70 ±2.10) d vs (14.10 ± 3.00) d, P = 0.006]. Delay EUS scan were likely to have higher white blood cell count and total bilirubin, meanwhile seemed to increase the organ failure rate and necrotic infection of the pancreas. Conclusion ABP with suspected obstructive jaundice should be considered to have endoscopy intervention. Results of EUS are the basis for treatment decision, which can avoid the unnecessary endoscopy treatment.