OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Nail-patella syndrome (NPS) is a hereditary rare disease that can involve fingernail, patella, elbow, and iliac bones. In this article, we report a case of a girl-9 and 1 quarter years old who had asthmatic contractures in both elbows, thumbnail hypoplasia in both hands, patellar dislocation of both knees, iliac angle protrusion of both sides, and scoliosis. Whole exome sequencing suggests the presence of a LMX1B NM_002316.4:c.706G > C(p.Ala236Pro) mutation. NPS is an autosomal dominant disease associated with gene mutation of LMX1B, which can be diagnosed by combining the patient′s clinical manifestations and genetic results. The treatment now only targets on symptoms, relieving the localized severe lesion but not cure right now.

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Objective To observe the clinical study of Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma. Methods A total of 268 patients with advance endometrial carcinoma in our hospital were divided into treatment group and control group, 134 cases in each group. The control group was treated by AP regimen and the treatment group was given Xiaoaiping tablet combined AP regimen. The treatment was 3 weeks per course, 4 periods performance, and the 2 year follow-up. After the treatment, the immune index, including IgG, IgA, IgM, CD3+ and CD4+ were detected by a chemical lighting method in the 2 groups. The KPS scores were observed to evaluate the life quality in the 2 groups. During the treatment, the adverse effects of chemotherapy in patients were observated during the treatment. And the survival rates, overall survival and progression-freely-survival were also observed. Results After the treatment, the control rate and efficiency rate were 86.5％ (116/134) and 64.2％(86/134) in treatment group, while the control rate and efficiency rate were 76.9％ (103/134) and 52.2％(70/134) in control group, where there were significantly difference in control rate and efficiency rate (Z values were 3.542 and 3.871, P values were 0.041 and 0.039). After the treatment, the levels of IgG, Ig A, IgM, CD3+ and CD4+ in treatment group were significantly higher than control group (t values were 4.725, 4.930, 4.259, 4.571 and 4.006, P<0.01). After the 1st-4th period of treatment, the KPS scores in treatment group were significantly higher than the control group (t values were 3.124, 3.452, 3.612 and 3.712, P<0.05). After the treatment, the PFS, OS, 1 year survival rate and 2 year survival rate were significantly lower in treatment group than control group (t values were 4.241, 4.421, 3.735 and 3.982, P<0.05). Conclusions The Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma has a good effect, could promote the immune function, decease the adverse effects and prolong the survival time in the patients.

Objective To explore the value of OTSC( over-the-scope-clip) for upper digestive tract perforation. Methods Thirteen patients with old and fresh upper digestive tract perforation, treated with an OTSC clip at the Department of Digestive Endoscopy from May 2015 to June 2016, were enrolled. All OTSCs were 11/6t, and all procedures were performed by experienced endoscopists. Results Seven cases of fresh perforation were iatrogenic after treatment for gastric submucosal tumor. Six cases of old perforation included 2 cases of spontaneous esophageal rupture, 2 fistula after operations for esophageal foreign body, 1 fistula after the operation for gastric stromal tumor, and 1 anastomotic fistula after esophagectomy. Eight cases of perforation occurred in stomach and 5 in esophageal. Fresh lesion sizes were from 4 to 30 mm ( average 15. 3 mm), old lesion sizes from 5 to 10 mm(average 7. 8 mm). OTSC′s release time in fresh lesions was 6-27 min(average 15. 1 min), that in old 15-80 min(average 42. 3 min) with significant difference. Technical success rate was 100％(13/13),clinical success rate in fresh lesions was 100％(7/7),and 50％ (3/6) in old lesions. No patient had special treatment or complication. Conclusion OTSC is useful and safe for the treatment of upper digestive tract perforation, which is superior for fresh perforation than for the old. The perfect time to release OTSC for old perforation is when there is no obvious fibrosis caused by inflammation. The success rate is higher when the lesion size is smaller than 30 mm. Self-releasing of OTSC is rare. The necessity and the timing to take them out still needs further study.

Objective To establish and compare HPLC fingerprint chromatograms of Dipsaci Radix decoction pieces, aqueous decoction and formula granules.Methods The HPLC analysis was carried out in Wondasil C18 column (4.6 mm × 250 mm, 5 μm) with a mobile phase of acetonitrile-0.1% phosphoric acid by gradient elution. The flow rate was 1.0 mL/min; the detection wavelength was set at 212 nm; the column temperature was kept at 30℃. Results The fingerprint chromatograms from 12 batches of Dipsaci Radix decoction pieces, aqueous decoction and formula granules were established respectively. 14 common peaks in the fingerprint chromatogram in the formula granules could be tracked in the aqueous decoction, and 13 common peaks in the fingerprint chromatogram could be tracked in the decoction pieces. 2 chemical compounds were identified, such as asperosaponinⅥ and chlorogenic acid.ConclusionThe method of HPLC fingerprint chromatograms is stable and with good repeatability. Dipsaci Radix decoction pieces, aqueous decoction and formula granules are basically the same chemical composition.

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.
Animals ; Brain ; Cell Movement ; physiology ; Cell Proliferation ; physiology ; Dendrites ; pathology ; Dentate Gyrus ; growth & development ; pathology ; Epilepsy, Temporal Lobe ; etiology ; pathology ; physiopathology ; Hippocampus ; growth & development ; pathology ; Humans ; Mitosis ; physiology ; Neurogenesis ; physiology ; Neurons ; pathology ; Seizures ; etiology ; physiopathology ; Status Epilepticus ; physiopathology

Objective To observe the dynamic change of serum levels of perioperative procalcitonin (PCT ) ,C-reactive protein (CRP) ,interleukin 6(IL-6) and N-terminal brain natriuretic peptide(NT-proBNP) in the patients with lung cancer and to evaluate their value in postoperative monitoring .Methods Seventy-two patients with lung cancer were detected PCT ,CRP ,IL-6 and NT-proBNP levels before operation and on postoperative 1-5 d .The detection results were compared between the patients with cardiac injury and infection complications .Results Postoperative levels of serum PCT ,CRP ,IL-6 and NT-proBNP were increased in all the patients ;the peak value appearance of PCT ,CRP ,IL-6 and NT-proBNP in the patients with complications were earlier than that in the patients without complications ,moreover the peak value was significantly higher than that in the patients without complications (P<0 .05);the decrease speed of PCT ,CRP ,IL-6 and NT-proBNP in the patients with complications was slower than that in the patients without complications .Conclusion The combined detection of PCT ,CRP ,IL-6 and NT-proBNP may be become an effec-tive means to differentiate the postoperative complications .

Objective To study the apoptosis of human colorectal cancer HT-29 cells induced by Aralia elata Seem leaf total saponin (ETS) and its effects on the expression of relevant proteins. Methods MTT assay was used to detect the proliferation of human colorectal cancer HT-29 cells cultivated with different concentrations (6.25, 12.5, 25, 50, 100, 200 mg/kg) of ETS. Hoechst33258 staining and laser confocal imaging were used to detect the apoptotic cells. Morphological changes were observed. The expressions of Bcl-2 and Bax were detected by immuno-histochemistry. Results ETS could induce apoptosis of HT-29 cells and apoptosis was in a dose-dependent manner in a certain range. ETS could decrease the expression of Bcl-2 and increase the expression of Bax in HT-29 cells (P<0.05, P<0.01), showing a significant dose-effect relationship. Conclusion ETS can induce the apoptosis of HT-29 cells, and the mechanism may be related to reducing the expression of Bcl-2 and increasing the expression of Bax.

OBJECTIVE:To train the students’ability about true-and-false identification of pini pollen,typhae pollen and Lygo-dium japonicum. METHODS:Teachers firstly used flexible and diversifided teaching methods to train the learning interest of stu-dents,and then picture antithesis,classroom presentation and other methods were used to teach the distinctive features between the true and false traditional Chinese medicine in the characters of identification. RESULTS&CONCLUSIONS:There were obvious dif-ference among the colors,physicochmical poperties,microscopic characteristics and other aspects of 3 traditional Chinese medi-cines. According to the teaching,the students could not only distinguish the 3 traditional Chinese medicines accurately, but also could identify the true-and-false of them. picture antithesis and classroom presentation method are simple and vivid, and can be used for the training of students’ability about true-and-false identification.