Application of hip capsule peripheral nerve block in early analgesia in elderly patients with hip fracture.

Objective: The objective of the study is to investigate the effect of pericapsular nerve group (PENG) block in early analgesia in elderly patients with hip fracture. Methods: A total of 44 elderly patients with hip fracture admitted to our hospital from August 2021 to December 2022 were selected and divided into 2 groups according to different analgesia programs. Results: At T1~T4, the resting and active visual analog scale (VAS) scores in group P were lower than group F (p < 0.05). The resting and active VAS scores at T5 in both groups were no visible differences (p > 0.05). After 30 min of block, systolic blood pressure, diastolic blood pressure, and heart rate were decreased in both groups (p < 0.05), but no obvious difference was found in the two groups (p > 0.05). Before surgery, Pittsburgh Sleep Quality Index (PSQI) and mini-mental state scale (MMSE) scores in both groups were reduced, and PSQI score in group P was lower than that in group F and MMSE score was higher than group F (p < 0.05). Conclusion: PENG technology is safe and effective in the early analgesia of elderly hip fractures. It can effectively block physiological stress response caused by acute trauma, improve pre-operative sleep quality, and reduce the incidence of cognitive dysfunction.

Objetivo: Investigar el efecto del bloqueo del grupo del nervio pericapsular en analgesia temprana en pacientes ancianos con fractura de cadera. Método: Se seleccionaron 44 pacientes ancianos con fractura de cadera ingresados en nuestro hospital entre agosto de 2021 y diciembre de 2022, divididos en dos grupos según diferentes programas de analgesia. Resultados: En T1~T4, los valores de la escala visual análoga (EVA) en reposo y con actividad en el grupo P fueron menores que en el grupo F (p < 0.05). Los puntajes de la EVA en reposo y en actividad en T5 en ambos grupos no mostraron diferencias visibles (p > 0.05). Después de 30 minutos de bloqueo, la presión arterial sistólica y diastólica, y la frecuencia cardiaca, disminuyeron en ambos grupos (p < 0.05), pero no se encontró una diferencia obvia entre ellos (p > 0.05). Antes de la cirugía, las puntuaciones del Pittsburgh Sleep Quality Index (PSQI) y de la Mini-Mental State Scale (MMSE) en ambos grupos eran reducidas, y la puntuación del PSQI en el grupo P fue menor que en el grupo F, y la puntuación del MMSE fue mayor que en el grupo F (p < 0.05). Conclusiones: La técnica de bloqueo del grupo del nervio pericapsular es segura y efectiva en la analgesia temprana de fracturas de cadera en ancianos. Puede bloquear eficazmente la respuesta al estrés fisiológico causado por un trauma agudo, mejorar la calidad del sueño preoperatorio y reducir la incidencia de disfunción cognitiva.

Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.

BACKGROUND: Increasing evidence suggests that chronic stress increases pain sensitivity and exacerbates existing pain. However, whether and how chronic unpredictable stress (CUS) affects surgical pain is unclear. METHODS: A postsurgical pain model was performed by longitudinal incision from 0.3 cm of the proximal edge of the heel toward the toes. The skin was sutured, and the wound site was covered. Sham surgery groups underwent the same procedure without an incision. The short-term CUS procedure was conducted by exposure of mice to 2 different stressors each day for 7 days. The behavior tests were conducted between 9:00 am and 4:00 pm. Mice were killed on day 19, and the mouse bilateral L4/5 dorsal root ganglia, spinal cord, anterior cingulate and insular cortex, and amygdala were collected for immunoblot analyses. RESULTS: Presurgical exposure of mice to CUS every day for 1-7 days showed significant depression-like behavior as evidenced by reduced sucrose preference in the sucrose consumption test and prolonged immobility time in the forced swimming task. This short-term CUS procedure did not affect the basal nociceptive response to mechanical and cold stimuli in the Von Frey and acetone-induced allodynia tests, but it delayed pain recovery after surgery, as indicated by the prolonged hypersensitivity in mechanical and cold stimuli by 12 days. The subsequent studies demonstrated that this CUS caused an increase in adrenal gland index. The abnormalities in pain recovery and adrenal gland index after surgery were reversed by a glucocorticoid receptor (GR) antagonist RU38486. Moreover, the prolonged pain recovery after surgery induced by CUS seemed to involve an increase in GR expression and decreases in cyclic adenosine monophosphate, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels in emotion-related brain regions, such as anterior cingulate and insular cortex, amygdala, dorsal horn, and dorsal root ganglion. CONCLUSIONS: This finding indicates that stress-induced GR change may result in dysfunction of GR-related neuroprotective pathway.

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications

To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization.MethodsImmunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice.ResultsThe clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. (AU)

Tumor-associated macrophages improve hypoxia-induced endoplasmic reticulum stress response in colorectal cancer cells by regulating TGF-ß1/SOX4.

Hypoxia is a common feature of solid tumors that can induce endoplasmic reticulum stress (ERS). This study aimed to explore the mechanism behind tumor-associated macrophages (TAMs) improving the ERS response of colorectal cancer (CRC) under hypoxic conditions. Herein, it was demonstrated that TAMs reduce ERS by secreting TGF-ß1 and activating SOX4/TMEM2 signaling in CRC cells. The expression levels of TGF-ß1, SOX4, and TMEM2 in 20 pairs of tumor tissues and para-carcinoma tissues were assessed. A co-culture system of CRC cells with THP-1-derived macrophages under hypoxic conditions in vitro was investigated to determine the protective effect of TAMs on CRC cells. Moreover, to further verify the underlying mechanism, TGF-ß1 and SOX4 were knocked down in the TAMs and CRC cells, respectively. The results exposed that TGF-ß1, SOX4, and TMEM2 were abundantly expressed in tumor tissues. Moreover, the co-culture system revealed that macrophages stimulate TGF-ß1 secretion under hypoxia, which depresses the CRC cells' ERS, further promoting cell proliferation and inhibiting apoptosis. Furthermore, increased TGF-ß1 levels promoted the expression of SOX4 and TMEM2 in CRC cells. Conversely, the knockdown of SOX4 attenuated the protective effect of TAMs on TGF-ß1-stimulated CRC cells. In conclusion, these results suggest that the elevated ERS induced by hypoxia in CRC cells could be relieved by TAMs via the secretion of TGF-ß1. Finally, TGF-ß1 suppresses undue ERS response in CRC cells by activating the SOX4-TMEM2 axis.

Effect of cell density on the malignant biological behavior of breast cancer by altering the subcellular localization of ANXA2 and its clinical implications.

OBJECTIVE: To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization. METHODS: Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice. RESULTS: The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells. CONCLUSION: Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.

Research on the Influence Mechanism of Personal Initiative on Enterprise Emergency Management Ability.

This study aims to explore the influence mechanism of personal initiative on the overall emergency management ability of enterprises so as to put forward effective measures to improve the emergency management ability. Based on social interaction theory and feature activation theory, the concepts of organizational support theory, executive power, and political skills were introduced to construct a corresponding theoretical model. We collected data through an online questionnaire to test this model via structural equation model analysis and regression analysis, with 208 participants of varying backgrounds. The results show that personal initiative can strengthen enterprise emergency management ability. The mediating effect of executive power between personal initiative and emergency management ability of enterprise has also been proved. In addition, the two adjustment variables of political skills and perceived organizational support both have a positive impact on the improvement of personal initiative and execution. Therefore, in order to improve the enterprise emergency management ability, it is suggested that enterprises should give full play to the personal initiative and improve the individual and overall executive power. The conclusion of this paper can provide new methodological support for improving emergency management ability.

Prevention of renal ischemia and reperfusion injury by penehyclidine hydrochloride through autophagy activation.

Penehyclidine hydrochloride (PHC) suppresses renal ischemia and reperfusion (I/R) injury (IRI); however, the underlying mechanism of action that achieves this function remains largely unknown. The present study aimed to investigate the potential role of autophagy in PHC­induced suppression of renal IRI, as well as the involvement of cell proliferation and apoptosis. A rat IRI model and a cellular hypoxia/oxygenation (H/R) model were established; PHC, 3­methyladenine (3­MA) and rapamycin (Rapa) were administered to the IRI model rats prior to I/R induction and to H/R cells following reperfusion. Serum creatinine was measured using a biochemistry analyzer, whereas aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) expression levels were detected using ELISA kits. Renal tissue injury was evaluated by histological examination. In addition, microtubule­associated protein light chain 3B (LC3B) expression, autophagosome formation, cell proliferation and apoptosis were detected in the cellular H/R model. The results demonstrated that I/R induced renal injury in IRI model rats, upregulated serum creatinine, ALAT and ASAT expression levels, and increased autophagic processes. In contrast, pretreatment with PHC or Rapa significantly prevented these I/R­induced changes, whereas the administration of 3­MA enhanced I/R­induced injuries through suppressing autophagy. PHC and Rapa increased LC3B and Beclin­1 expression levels, but decreased sequestome 1 (p62) expression in the cellular H/R model, whereas 3­MA prevented these PHC­induced changes. PHC and Rapa promoted proliferation and autophagy in the cellular H/R model; these effects were accompanied by increased expression levels of LC3B and Beclin­1, and reduced p62 expression levels, whereas these levels were inhibited by 3­MA. Furthermore, PHC and Rapa inhibited apoptosis in the cellular H/R model through increasing Bcl­2 expression levels, and suppressing Bax and caspase­3 expression levels; the opposite effect was induced by 3­MA. In conclusion, PHC suppressed renal IRI through the induction of autophagy, which in turn promoted proliferation and suppressed apoptosis in renal cells.

[Protection of penehyclidine hydrochloride on renal tissue injury induced by limb ischemia/reperfusion].

OBJECTIVE: To evaluate the protection of penehyclidine hydrochloric postconditioning on HIF-1α (hypoxia-inducible factor-1α) in renal tissue injury induced by lower limb ischemia/reperfusion (I/R). METHODS: A total of 72 adult male Wistar rats weighing 230 - 250 g were randomly divided into 3 groups: control (group C), limb ischemia-reperfusion (group R/I) and penehyclidine hydrochloride postconditioning (group P). The animals were anesthetized by inhaling 2% isoflurane and blood flow of bilateral lower limbs was blocked with rubber bands for 3 h in groups P and R/I. In group P, penehyclidine hydrochloride 0.15 mg/kg was injected via caudal vein at 3 min pre-reperfusion. After sacrificing, their kidneys were removed at 3 h of ischemia and 1, 3, 6 h of reperfusion respectively. The blood urea nitrogen (BUN) and creatinine (Cr) were detected by colorimetric method, plasma tumor necrosis factor-α (TNF-α) by ELISA (enzyme-linked immunosorbent assay) and HIF-1α of renal tissue by immunohistochemistry. Renal pathological changes were observed under light microscope. RESULTS: Compared with group C, the serum levels of BUN and Cr increased while TNF-α and HIF-1α were up-regulated in groups I/R and P (P < 0.05). As compared with group I/R, the serum levels of BUN, Cr and MDA decreased while TNF-α and HIF-1α were down-regulated in group P. [at T2: (15.10 ± 1.88) mmol/L vs (19.46 ± 2.76) mmol/L, (113 ± 10) µmol/L vs (143 ± 11) µmol/L, (13.8 ± 1.7) nmol/g vs (15.5 ± 1.8) nmol/g, (53.1 ± 3.1) ng/L vs (53.9 ± 4.8) ng/L, 0.298 ± 0.015 vs 0.471 ± 0.032, all P < 0.05]. CONCLUSION: Penehyclidine hydrochloride can down-regulate the expression of HIF-1α and attenuate the renal injury induced by lower limb I/R. And the mechanisms may be through inhibiting the inflammatory reactions, reducing the release of oxygen free radicals and improving the conditions of hypoxia and ischemia.

[Preventive effects of ischemic postconditioning and penehyclidine hydrochloride on gastric against ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effects of ischemic postconditioning and penehyclidine hydrochloride on gastric injury induced by ischemia-reperfusion of lower limb in rats. METHODS: The model of limb ischemia reperfusion injury was used to perform this experiment. One hundred and forty four male Wistar rats weighing 220 - 250 g were randomly divided into 4 groups: group I Control (C), group II Ischemic Reperfusion (IR), group III Ischemic postconditioning (IPO) and group IV penehyclidine hydrochloride (IPHC); C, IR, IPO and IPHC groups has been followed for 0(T(0)), 1(T(1)), 3(T(3)), 6(T(6)), 12(T(12)), or 24(T(24)) perfusion, all the groups were secondary separated into six subgroups as time point and each subgroup contained six rats, respectively. Blood samples from the inferior vena cava were taken for determination of LDH, CK activities and TNF-α, IL-10 content at every time point of reperfusion;the animals were killed at every time point respectively and the gastric were removed for determination of SOD, MPO, XOD and LDH activities, MDA content, and histological examination and the expression of HIF-1α was analyzed. RESULTS: Compared with group C, IR, IPO and IPHC, in serum LDH and CK activities were increased, TNF-α and IL-10 content were increased (P < 0.05 or P < 0.01); and in gastric tissue MPO, XOD and LDH activities were increased and MDA content increased, while SOD activity decreased in group IR, IPO and IPHC (P < 0.05 or P < 0.01); and gastric tissue resulted in significant injury as evidenced by infiltrated of few neutrophils or eosinophils and rare neutrophils between the gastric mucosa or muscularis mucosa and the glands, interstitial vascular dilation hyperemia and small quantity hemorrhage from deep layers of mucosa or interstitial vascular dilation hyperemia, and the expression of HIF-1α was significantly increased (P < 0.01). Compared with group IR, IPO and IPHC in serum LDH and CK activities, TNF-α content decreased while IL-10 content were increased (P < 0.01); and in gastric tissue MDA content, MPO, XOD and LDH activities were decreased, and SOD activity increased in group IPO and IPHC (P < 0.05 or P < 0.01); and the histological injury were milder and the expression of HIF-1α was significantly decreased (P < 0.01). Compared with group IPO, IPHC, in serum LDH activities were makable decreased, CK activities were first increased and then declined, TNF-α content makable declined while IL-10 content were increased (P < 0.05 or P < 0.01), and the histological injury were milder and the expression of HIF-1α was makable decreased (P < 0.01) and in gastric tissue SOD activity were makable increased, MPO activities significantly decreased, MDA content increased at T(3), XOD activities increased after T(12), LDH activities increased at T(3) and declined after T(12) in group IPHC (P < 0.05 or P < 0.01). CONCLUSION: The combination of ischemia postconditioning and postconditioning with penehyclidine hydrochloride can protect the gastric from ischemia-reperfusion injury induced by ischemia reperfusion of the lower limbs in rats, the main mechanism may be reducing post-ischemic oxidative damage, inflammatory reaction, amelio-rating microcirculatory and cellular energy metabolism et al. Additionally, this study found that the protective effects of penehyclidine hydrochloride on gastric injury induced by ischemia reperfusion of the lower limbs, were better than ischemic postconditioning, and the mechanism might be related to its anti-inflammatory effect, antioxidant action and prevention of cell injury et al.

Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia.

AIM: To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS: The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0, 1, 3, 6, 12 or 24 h. Ischemic post-conditioning, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damage and the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays. RESULTS: Ischemic post-conditioning can reduce post-ischemic oxidative stress and the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA, SOD, XOD and MPO were regarded as indexes for mucosal injuries from ROS, and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions. CONCLUSION: ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore, ROS can regulate HIF-1α expression in gastric ischemia.

Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion.

AIM: To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion (LIR) injury. METHODS: Male Wistar rats were randomly divided into three groups (36 rats each): the sham-operation group (group S), lower limb ischemia-reperfusion group (group LIR), and penehyclidine hydrochloride post-conditioning group (group PHC). Each group was divided into subgroups (n = 6 in each group) according to ischemic-reperfusion time, i.e. immediately 0 h (T1), 1 h (T2), 3 h (T3), 6 h (T4), 12 h (T5), and 24 h (T6). Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h. In group PHC, 0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia. The designated rats were sacrificed at different time-points of reperfusion; diamine oxidase (DAO), superoxide dismutase (SOD) activity, myeloperoxidase (MPO) of small intestinal tissue, plasma endotoxin, DAO, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 in serum were detected in the rats. RESULTS: The pathological changes in the small intestine were observed under light microscope. The levels of MPO, endotoxin, serum DAO, and IL-10 at T1-T6, and TNF-α level at T1-T4 increased in groups LIR and PHC (P < 0.05) compared with those in group S, but tissue DAO and SOD activity at T1-T6 decreased (P < 0.05). In group PHC, the tissue DAO and SOD activity at T2-T6, and IL-10 at T2-T5 increased to higher levels than those in group LIR (P < 0.05); however, the levels of MPO, endotoxin, and DAO in the blood at T2-T6, and TNF-α at T2 and T4 decreased (P < 0.05). CONCLUSION: Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR. Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.