Inhibition of MMP-2 and MMP-9 attenuates surgery-induced cognitive impairment in aged mice.

BACKGROUND: The inhibition of matrix metalloproteinases (MMPs) has shown potential in the treatment of various neurodegenerative diseases, and perioperative neurocognitive disorders (PND) is accompanied by the increased expression of MMP-2 and MMP-9 in the hippocampus. However, the effect of inhibiting MMP-2 and MMP-9 on PND is not clear. In this study we aimed to evaluate the effects of inhibiting MMP-2 and MMP-9 on cognitive function in the aged mice after surgery, in order to find a possible target for the prevention and treatment of PND METHODS: In this study, 14-month-old C57BL/6 mice were used to establish a PND model by tibial fracture surgery and sevoflurane anesthesia. Three days later, part of the mice were subjected to cognitive assessment and the other was sacrificed for biochemical analysis. We used the Novel object recognition test and Fear conditioning test to evaluate the postoperative cognitive function of mice. The expression of mmp-2 and MMP-9 was detected by western blotting. We also examined the expression of claudin-5 and occludin using Western blotting, and the activation of microglia and astrocytes using immunofluorescence. RESULTS: The results showed that surgery increased the expression of MMP-2 and MMP-9 in the hippocampus of mice, accompanied by cognitive impairment, decreased expression of claudin-5 and occludin, and increased activation of microglia and astrocytes. However, inhibition of MMP-2 and MMP-9 expression by SB-3CT reversed these changes. CONCLUSIONS: Our study shows that inhibition of MMP-2 and MMP-9 alleviates anesthesia/surgery-induced cognitive decline by increasing BBB integrity and inhibiting glial cell activation.

Utilization of deep neuromuscular blockade combined with reduced abdominal pressure in laparoscopic radical gastrectomy for gastric cancer: An academic perspective.

BACKGROUND: Few studies have examined the specific efficacy of deep neuromuscular blockade (NMB) combined with pneumoperitoneal pressure reduction in laparoscopic radical gastrectomy (LRG) in the elderly. AIM: To investigate the application effect of deep neuromuscular blockade (NMB) combined with reduced pneumoperitoneum pressure in LRG for gastric cancer (GC) in elderly patients and its influence on inflammation. METHODS: Totally 103 elderly patients with GC treated in our hospital between January 2020 and January 2022 were retrospectively analyzed. Among them, 45 patients treated with surgery based on deep NMB and conventional pneumoperitoneum pressure were assigned to the control group, while the rest of the 58 patients who underwent surgery based on deep NMB and reduced pneumoperitoneum pressure were assigned to the observation group. The two groups were compared in the changes of the Leiden-surgical rating scale score, serum tumor necrosis fact-α (TNF-α) and interleukin 6 (IL-6) before and after therapy. The visual analogue scale (VAS) was adopted for evaluating the shoulder pain of patients at 8 h, 24 h and 48 h after the operation. The driving pressure of the two groups at different time points was also compared. Additionally, the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room, TOF% = 90% time and post-anesthetic recovery room (PACU) stay time were all recorded, and adverse PACU-associated respiratory events were also recorded. The postoperative hospitalization time and postoperative expenses of the two groups were counted and compared. RESULTS: No significant difference was found between the two groups at the time of skin incision, 60 minutes since the operation and abdominal closure after surgery (P > 0.05). The observation group exhibited significantly lower VAS scores than the control group at 24 and 48h after surgery (P < 0.05). Additionally, the observation group had significantly lower driving pressure than the control group at 5 min and 60 min after the establishment of pneumoperitoneum (P < 0.05). Additionally, the two groups were similar in terms of the operation time, pneumoperitoneum time, infusion volume, blood loss, extubation time after surgery, residence time in the resuscitation room and TOF% = 90% time (P > 0.05), and the observation group showed significantly lower TNF-α and IL-6 Levels than the control group at 24 h after therapy (P < 0.05). Moreover, the incidence of adverse events was not significantly different between the two groups (P > 0.05), and the observation group experienced significantly less hospitalization time and postoperative expenses than the control group (P < 0.05). CONCLUSION: Deep NMB combined with reduced pneumoperitoneum pressure can decrease the VAS score of shoulder pain and inflammatory reaction, without hindering the surgical vision and increasing adverse PACU-associated respiratory events, and can thus shorten the hospitalization time and treatment cost for patient.

A mandible from the Middle Pleistocene Hexian site and its significance in relation to the variability of Asian Homo erectus.

OBJECTIVES: This study presents the first detailed morphological description and comparison of a Middle Pleistocene hominin mandibular fragment (PA 831) and associated teeth from the Hexian site in Eastern China. We aim to investigate where the Hexian mandible fits within the genus Homo variability in the light of an increased and better characterized Asian fossils record. METHODS: Comparative samples include Pleistocene Homo mandibles and teeth from Africa, Asia, and Europe, as well as earlier African hominins (Australopithecus and early Homo) and Holocene recent humans. Both conventional morphological description and metric analysis were used. In addition, virtual reconstructions of the enamel dentine junction (EDJ) surface, pulp cavity, and roots with micro-CT were used to the mandible and teeth. RESULTS: The Hexian mandible is characterized by a plesiomorphic structural pattern for the Homo clade, with strong corpus robustness and a subparallel and low-positioned mylohyoid line that differentiates the swollen subalveolar planum from the shallow subalveolar fossa. Features that are derived compared to early Homo include a moderately curved dental arcade, a well-developed lateral prominence placed at the M2 -M3 level, and multiple mental foramina. The Hexian mandible's complex enamel surface and strong, stout root structure are primitive traits for the Homo clade. Finally, the highly crenulated "dendrite-like" EDJ found in the molars may represent a dental feature specific to the continental Asian Homo erectus, but more data is needed to confirm this. CONCLUSIONS: Mandibular and dental features indicate that the Hexian mandible and teeth differ from northern Chinese H. erectus and European Middle Pleistocene hominins, but show some affinities with the Early Pleistocene specimens from Africa (Homo ergaster) and Java (H. erectus), as well as the Middle-Late Pleistocene mandible from Penghu, Taiwan. Compared to contemporaneous continental Asian hominin populations, the Hexian fossils may represent the survival of a primitive hominin, with more primitive morphologies than other contemporaneous or some chronologically older Asian hominin specimens.

Middle Pleistocene hominin teeth from Longtan Cave, Hexian, China.

Excavations at the Longtan Cave, Hexian, Anhui Province of Eastern China, have yielded several hominin fossils including crania, mandibular fragments, and teeth currently dated to 412 ± 25 ka. While previous studies have focused on the cranial remains, there are no detailed analyses of the dental evidence. In this study, we provide metric and morphological descriptions and comparisons of ten teeth recovered from Hexian, including microcomputed tomography analyses. Our results indicate that the Hexian teeth are metrically and morphologically primitive and overlap with H. ergaster and East Asian Early and mid-Middle Pleistocene hominins in their large dimensions and occlusal complexities. However, the Hexian teeth differ from H. ergaster in features such as conspicuous vertical grooves on the labial/buccal surfaces of the central incisor and the upper premolar, the crown outline shapes of upper and lower molars and the numbers, shapes, and divergences of the roots. Despite their close geological ages, the Hexian teeth are also more primitive than Zhoukoudian specimens, and resemble Sangiran Early Pleistocene teeth. In addition, no typical Neanderthal features have been identified in the Hexian sample. Our study highlights the metrical and morphological primitive status of the Hexian sample in comparison to contemporaneous or even earlier populations of Asia. Based on this finding, we suggest that the primitive-derived gradients of the Asian hominins cannot be satisfactorily fitted along a chronological sequence, suggesting complex evolutionary scenarios with the coexistence and/or survival of different lineages in Eurasia. Hexian could represent the persistence in time of a H. erectus group that would have retained primitive features that were lost in other Asian populations such as Zhoukoudian or Panxian Dadong. Our study expands the metrical and morphological variations known for the East Asian hominins before the mid-Middle Pleistocene and warns about the possibility that the Asian hominin variability may have been taxonomically oversimplified.