Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Hepato-pancreato-biliary diseases (HPBD) are often complicated. The diagnosis and treatment of HPBD involve many disciplines. The malignant degree of hepatobiliary pancreatic system is high, and the prognosis of patients is poor. The multidisciplinary team (MDT) brings specialists from different disciplines together to make a comprehensive and individualized treatment for patients. MDT is emerging in HPBD in recent years. MDT helps improve the accuracy of diagnosis and prognosis. However, there are still some controversies and obstacles in the application of MDT for patients with HPBD. We reviewed the development, current status and experience of MDT in the field of HPBD, analyze the current controversy and obstacles, and providing reference for its future application.

Objective:To investigate the effectiveness of antibiotics in preventing surgical site infection (SSI) after hepatectomy.Methods:The clinical data of patients who underwent hepatic resection at the Department of Biliary and Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, from Jan 2019 to Dec 2021, were retrospectively analyzed.Results:A total of 509 patients were included in the study. There was no statistically significant difference in the incidence of SSI in the different prophylactic treatment time groups ( P>0.05). Univariate analysis revealed bile leakage, extent of hepatic resection, surgical procedure, level of anesthesia, and duration of surgery as potential risk factors for SSI after hepatic resection ( P<0.05); Multivariate analysis showed that bile leakage, extensive hepatic resection, open surgical approach, grade 3-4 anesthesia level, and operative time longer than 300 minutes might be independent risk factors affecting SSI after hepatectomy ( P<0.05). Conclusion:Prolonging antibiotic prophylaxis for SSI after hepatectomy may be unnecessary.

Objective     To explore the causes of conversion to thoracotomy in patients with minimally invasive esophagectomy (MIE) in a surgical team, and to obtain a deeper understanding of the timing of conversion in MIE. Methods     The clinical data of patients who underwent MIE between September 9, 2011 and February 12, 2022 by a single surgical team in the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. The main influencing factors and perioperative mortality of patients who converted to thoracotomy in this group were analyzed. Results     In the cohort of 791 consecutive patients with MIE, there were 520 males and 271 females, including 29 patients of multiple esophageal cancer, 156 patients of upper thoracic cancer, 524 patients of middle thoracic cancer, and 82 patients of lower thoracic cancer. And 46 patients were converted to thoracotomy for different causes. The main causes for thoracotomy were advanced stage tumor (26 patients), anesthesia-related factors (5 patients), extensive thoracic adhesions (6 patients), and accidental injury of important structures (8 patients). There was a statistical difference in the distribution of tumor locations between patients who converted to thoracotomy and the MIE patients (P<0.05). The proportion of multiple and upper thoracic cancer in patients who converted to thoracotomy was higher than that in the MIE patients, while the proportion of lower thoracic cancer was lower than that in the MIE patients. The perioperative mortality of the thoracotomy patients was not significantly different from that of the MIE patients (P=1.000). Conclusion     In MIE, advanced-stage tumor, anesthesia-related factors,extensive thoracic adhesions, and accidental injury of important structures are the main causes of conversion to thoracotomy. The rate varies at different tumor locations. Intraoperative conversion to thoracotomy does not affect the perioperative mortality of MIE.

Objective To establish an animal model of postmortem redistribution of amantadine,and to study its postmortem redistribution in rats,so as to provide experimental evidence for forensic identification.Methods One hundred and twenty-six male SD rats were randomly divided into 3 groups and subjected to intragastric administration according to the maximum dose of treatment(L),LD50(M)and 2LD50(H).Those who did not die were killed according to the average time of death of LD50.Heart-blood,peripheral blood,heart,liver,spleen,lung,kidney,brain,muscle and testis were collected at 0 h,6 h,12 h,24 h,48 h,72 h and 96 h after death,and amantadine content was detected.Results For the rats in the L group,the concentration of amantadine decreased within 6 h after death and then increased in the heart-blood,heart and liver,unchanged within 48 h and reached the peak at 96 h in the spleen,kidney,brain,muscle and testis,while decreased in the lung.For the rats in the M group,the concentration of amantadine decreased within 24 h after death and then increased in all samples,and it reached the peak at 48 h after death in the peripheral blood,spleen,kidney and muscle tissues,at 72 h after death in the heart-blood and testis,and at 96 h after death in the liver,lung and brain tissues.For the rats in the H group,the concentration of amantadine showed a downward trend within 12 h after death in the heart and liver tissue,showed a downward trend within 48 h after death in the lung,brain and muscle tissue,and reached the peak at 96 h after death in the heart,liver,spleen,muscle and testicle tissues.Conclusion The postmortem redistribution was found in amantadine poisoning dead rats,which could provide experimental evidence for the forensic identification of death cases caused by amantadine poisoning.

Objective:To investigate the regulation of melatonin(MT)against lung injury in a mouse model of influenza virus infection by regulating the maternally expressed gene 3(MEG3)/microRNA-223(miR-223)/nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)axis.Methods:Fifty mice were randomly divided into control group,model group,and MT(low,medium,and high)dose groups,with 10 mice in each group.Except for the control group,the other groups were given H7N9 virus suspension nasal drops at a dose of 5×105 EID50,and the control group was given an equal volume of phosphate buffer nasal drops.The MT(low,medium,and high)dose groups were injected intraperitoneally with(15,30,60)mg/kg MT on the day after modeling,the control group and model group were intraperitoneally injected with equal volume of normal saline.The mice were sacri-ficed 24 h after the last administration for experiment.All mice were tested for the lung index;Hematoxylin-Eosin(HE)staining was used to observe the lung tissue morphology;ELISA was used to detect the levels of interleukin IL-1β,IL-18,IL-6,TNF-α and IFN-β in lung tissues;real-time fluorescent quantitative PCR(RT-qPCR)was used to detect the levels of MEG3 mRNA and miR-223 in mouse lung tissues;Western blot was used to detect the protein levels of NLRP3,apoptosis-related dot-like protein(ASC),cysteine aspartate proteolytic enzyme 1(caspase-1),and pro-caspase-1 in lung tissues.Bioinformatics prediction and dual luciferase experi-ments were used to detect the targeting relationship between MEG3 and miR-223,miR-223 and NLRP3.Results:The pathological re-sults showed that the alveolar wall of the lung tissue of the model group was obviously congested,and there was obvious inflammatory exudation and inflammatory cell infiltration in the cavity;with the increase of the MT dose,the hyperemia of the alveolar wall of the mouse lung tissue,the inflammatory exudation in the cavity and the infiltration of inflammatory cells in the MT(low,medium,and high)dose group were all improved.Compared with control group,the lung index,chemokines,inflammatory factors,antiviral fac-tors,MEG3 levels in lung tissues,NLRP3 pathway protein level in the model group were increased(P<0.05),and the miR-223 level was decreased(P<0.05);after the addition of MT,the antiviral factors increased significantly,and other indicators were improved.miR-223 had targeted regulatory relationships with MEG3 and NLRP3.Conclusion:MT can alleviate the lung injury of H7N9 influen-za virus-infected mice,which may be related to the regulation of MEG3/miR-223/NLRP3 axis to relieve inflammation.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

Background::The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients.Methods::The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared.Results::For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE ( n = 204) and OE groups ( n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs. 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs. 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs. 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs. 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs. 3.9% [2/51], P= 0.031) subgroups. Conclusion::MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.

Objective:To discuss the influence of high load and weightlessness environment on intervertebral disc by observing and analyzing the imaging changes of the spines in New Zealand white rabbits and the content changes of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in the intervertebral disc under high load and weightlessness environment, and to provide theoretical basis for prevention and delay of lumbar intervertebral disc degeneration under high load and weightlessness environment.Methods:A total of 120 New Zealand white rabbits with balanced age and body weight were randomly and averagely divided into control groups (further grouped by 30 d, 60 d and 90 d) and high load/weightlessness groups (further grouped by 30 d, 60 d and 90 d) with residual single-blind method. High load was simulated by animal centrifuge and weightlessness was simulated by tail suspension. The imaging changes and the positive expression rates of MMP1, MMP3 and TIMP1 in intervertebral disc were detected, and the statistical differences between the high load/weightlessness group and the control group in different time periods were compared, as well as among the different exposure time in load/weightlessness groups.Results:From the imaging observation, the T2-weighted images of lumbar 6 sacral 1 intervertebral disc in experimental animals decreased to some extent. The positive rates of MMP1 and MMP3 in each high load/weightlessness group were higher than those in the control group for the same exposure time, and the differences were statistically significant ( t=22.97-145.51,all P<0.001). The positive rates of MMP1 and MMP3 increased with the extension of exposure time, and there were statistically differences among the groups with different exposure time in high load/weightlessness group ( F=2531.10, 1758.80, both P<0.001). The positive rate of TIMP1 in each high load/weightlessness group was higher than that in the control group for the same exposure time, and the difference was statistically significant ( t=29.34-65.05, all P<0.001). There was statistically difference on TIMP1 positive rate among different load/weightlessness exposure time groups ( F=462.20, P<0.001). Conclusions:High load/weightlessness can cause the MMP1, MMP3 and TIMP1 content changes in animal lumbar disc. The changes of TIMP1 are obvious in the early stage and the sensitivity is decreased in the late stage. High load/weightlessness may lead to changes in the contents of MMP and TIMP in intervertebral discs, which may accelerate intervertebral disc degeneration.

Objective:To discuss the influence of high load and weightlessness environment on intervertebral disc by observing and analyzing the imaging changes of the spines in New Zealand white rabbits and the content changes of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in the intervertebral disc under high load and weightlessness environment, and to provide theoretical basis for prevention and delay of lumbar intervertebral disc degeneration under high load and weightlessness environment.Methods:A total of 120 New Zealand white rabbits with balanced age and body weight were randomly and averagely divided into control groups (further grouped by 30 d, 60 d and 90 d) and high load/weightlessness groups (further grouped by 30 d, 60 d and 90 d) with residual single-blind method. High load was simulated by animal centrifuge and weightlessness was simulated by tail suspension. The imaging changes and the positive expression rates of MMP1, MMP3 and TIMP1 in intervertebral disc were detected, and the statistical differences between the high load/weightlessness group and the control group in different time periods were compared, as well as among the different exposure time in load/weightlessness groups.Results:From the imaging observation, the T2-weighted images of lumbar 6 sacral 1 intervertebral disc in experimental animals decreased to some extent. The positive rates of MMP1 and MMP3 in each high load/weightlessness group were higher than those in the control group for the same exposure time, and the differences were statistically significant ( t=22.97-145.51,all P<0.001). The positive rates of MMP1 and MMP3 increased with the extension of exposure time, and there were statistically differences among the groups with different exposure time in high load/weightlessness group ( F=2531.10, 1758.80, both P<0.001). The positive rate of TIMP1 in each high load/weightlessness group was higher than that in the control group for the same exposure time, and the difference was statistically significant ( t=29.34-65.05, all P<0.001). There was statistically difference on TIMP1 positive rate among different load/weightlessness exposure time groups ( F=462.20, P<0.001). Conclusions:High load/weightlessness can cause the MMP1, MMP3 and TIMP1 content changes in animal lumbar disc. The changes of TIMP1 are obvious in the early stage and the sensitivity is decreased in the late stage. High load/weightlessness may lead to changes in the contents of MMP and TIMP in intervertebral discs, which may accelerate intervertebral disc degeneration.