Cyclin D1 mediates pain behaviour in a rat model of breast cancer-induced bone pain by a mechanism involving regulation of the proliferation of spinal microglia.

AIMS: The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. METHODS: Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. RESULTS: IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. CONCLUSION: Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP.Cite this article: Bone Joint Res 2022;11(11):803-813.

Efficacy of Pre-Treatment with Remimazolam on Prevention of Propofol-Induced Injection Pain in Patients Undergoing Abortion or Curettage: A Prospective, Double-Blinded, Randomized and Placebo-Controlled Clinical Trial.

BACKGROUND: Propofol-induced injection pain (PIP) is a well-known problem in general anesthesia. We hypothesized that pre-treatment with remimazolam prevents PIP in patients undergoing abortion or curettage. MATERIALS AND METHODS: In this prospective, single-center, double-blinded, randomized, placebo-controlled clinical trial, adult patients aged 18 to 60 undergoing abortion or curettage were randomly assigned to three groups. Group Lido received system lidocaine (a bolus of 0.5 mg kg-1, iv). Group Remi received remimazolam (a bolus of 0.1 mg kg-1, iv). Group NS received identical volumes of 0.9% normal saline. Sixty seconds after the injection of lidocaine, remimazolam or saline, patients were injected with propofol at a rate of 12 mL/min until the loss of consciousness. The primary outcome was the incidence of PIP at the time of induction using 4-point scale. Secondary outcomes included propofol-induced injection pain, vital signs, the characteristics of anesthesia and surgery, and adverse events. RESULTS: The incidence of patients with PIP was higher in group NS than that in group Lido and group Remi (75.7, 44.3, and 42.9%, respectively, p < 0.001). The percentages of patients with moderate PIP were higher in group NS than that in group Lido and group Remi (20.0, 2.9, and 1.4%, respectively, p < 0.001). Moreover, the consumption of propofol and the incidence of adverse event (hypoxemia and chin lifting) in group Remi were lower than that in group NS and Lido, and less patients got physical movement and cough in group Remi. The recovery time in group NS was longer than that in group Lido and Remi. CONCLUSION: Our findings indicate that pre-treatment with remimazolam reduced the incidence and intensity of PIP in abortion or curettage patients, equivalent to that of lidocaine without severe adverse effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR2100041805).

Study on Interference Connection Based on Shape Recovery of NiTiNb Shape Memory Alloy.

Interference connection is an effective method for improving the fatigue life of bolt connections. In this paper, a new method of interference connection was designed based on the shape memory effect of shape memory alloy. Using the method of numerical simulation, a finite element model was established to analyze the stress-strain rule of the bolt and the hole wall under different interference fit sizes. The results show that the stress concentration is formed at the orifice of the connecting plate. When the interference fit size is less than 1%, the connection hole has elastic deformation. When the interference fit size is 1.5%, the hole wall has plastic deformation. When the interference fit size is 2.5%, the maximum stress on the connecting plate is close to the tensile limit of the material. If the interference fit size continues to increase, the strength of the connection structure will be damaged. The connection experiments with different interference fit size were designed, and the interference force was calculated by the pull-out force. The experimental results were compared with the numerical simulation results. The change trend of the interference force with the interference fit size is consistent, which verifies the rationality of the finite element simulation.

Dose-dependent neurotoxicity caused by the addition of perineural dexmedetomidine to ropivacaine for continuous femoral nerve block in rabbits.

OBJECTIVE: This study was designed to evaluate the neurotoxicity of dexmedetomidine combined with ropivacaine for continuous femoral nerve block in rabbits. METHODS: Thirty New Zealand rabbits were randomly divided into 5 groups of 6 rabbits each and received a continuous femoral nerve block with saline; 0.25% ropivacaine; or 1, 2, or 3 µg/mL of dexmedetomidine added to 0.25% ropivacaine (Groups A-E, respectively). Sensory and motor function was assessed after the nerve block. The rabbits were anesthetized and killed after 48 hours of a continuous femoral nerve block, and the femoral nerves were removed for light and electron microscopy analyses. RESULTS: The behavior scores were highest in Group A at 2 and 6 hours after injection. The scores were higher in Groups B and C than in Groups D and E at these same time points. All groups showed normal pathological tissues in the femoral nerves under optical microscopy. Under electron microscopy, histological abnormalities were observed only in Group E; none of the other groups exhibited pathological abnormalities. Quantitative analysis of the myelin sheath area revealed no significant difference in the axonal area, total area of the myelin sheath, or ratio of the total axonal area to the total area of the myelin sheath in all groups. CONCLUSION: The lowest doses of dexmedetomidine (1 and 2 µg/mL) combined with 0.25% ropivacaine for continuous femoral nerve block resulted in no neurotoxic lesions, but the higher dose (3 µg/mL) resulted in neurotoxic lesions in this rabbit experimental model.

The effect of pre-process and transport strategies on survival, microbiologic, and physiologic of Patinopecten yessoensis.

The supply chain of shellfish is complex, with animals being subjected to several stressors during the depuration, temporary keeping, and waterless-low-temp transportation processing. In this paper, the recycled water system for depuration and temporary keeping was used to realize both depuration and temporary keeping of Patinopecten yessoensis. The samples were divided into three groups based on three different pre-process involved: samples in group 1 were depurated for 48 hr straight, whereas those in group 2 were first depured for 24 hr and then cooled for 24 hr; samples in group 3 was directly kept in a polyethylene insulation box. Then group 1 and group 2 were transported in a 3L polyethylene insulation box with ice packs (250 ml) to study the quality of transport based on the different pre-process. As a result, in group 1 (depuration for 48 hr), the first death occurred after 56 hr, and all shellfishes died after 102 hr with total bacterial density of 2,630 CFU/ml. In group 2 (depuration for 24 hr and temporary keeping for 24 hr), the first death occurred after 104 hr and the total number of bacteria was increasing steadily within 0-104 hr. After 120 hr, all shellfishes died with total bacterial density of 1,090 CFU/ml. In group 3 (directly transport), all shellfishes died in 64 hr. The total number of bacteria in groups 1 and 2 declined significantly in the depuration process. The bacteria number (p < 0.05) in group 3 was significantly different from that in groups 1 and 2. The crude protein, crude fat, and glycogen of all groups declined. However, compared to groups 1 and 3, the consumption of glycogen in group 2 (p < 0.05) was delayed by the gradual cooling procedure. Those results prove that the depuration and temporary keeping procedures can improve the sterilization of the bacteria. The survival rate is less sensitive to the temperature change. The results provide satisfactory references for the P. yessoensis' quality studies with depuration, temporary keeping, and waterless-low-temp transportation technologies.

Mechanical Properties Study of Fe-Mn-Si Shape Memory Alloys Welding Seam Formed by Laser Welding with Filler Powder.

To reduce the residual stress and improve the fatigue property of the laser weldment by using the stress self-accommodation characteristic of Fe-Mn-Si shape memory alloys (SMAs), a Fe15Mn5Si12Cr6Ni memory alloy welding seam was formed inside 304 stainless steel by laser welding with filler powder. The combination of the hole-drilling method and the ANSYS software was used to research the distribution law of residual stress inside the laser welding specimen. The fatigue strength of the laser welded specimens with the Fe-Mn-Si SMAs welding seam (experimental materials) and 304 stainless steel welding seam (comparative materials) was measured by cycle bending fatigue test. The microhardness of the welding specimens was measured by the microhardness tester. The thermodynamic model of the laser welding process and the phase transition crystallography of Fe-Mn-Si SMAs were evaluated to analyze the strengthening mechanism of the mechanical properties in the experimental materials. The results show that the distribution law for residual stress in the experiment and simulation are consistent. The experimental materials possess low residual stress, high fatigue strength and high microhardness. The strengthening mechanism for mechanical properties is the welding residual stress-induced γ→ε martensitic transformation inside the experimental materials, which causes the tensile plastic strain of the welding seam to resist residual compression strain, and the residual stress, as the transition driving force, is released in shear processing.

Optimal central venous pressure during partial hepatectomy for hepatocellular carcinoma.

BACKGROUND: Low central venous pressure (CVP) affects hemodynamic stability and tissue perfusion. This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma (HCC). METHODS: Ninety-seven patients who underwent partial hepatectomy for HCC had their CVP controlled at a level of 0 to 5 mmHg during hepatic parenchymal transection. The systolic blood pressure (SBP) was maintained, if possible, at 90 mmHg or higher. Hepatitis B surface antigen was positive in 90 patients (92.8%) and cirrhosis in 84 patients (86.6%). Pringle maneuver was used routinely in these patients with clamp/unclamp cycles of 15/5 minutes. The average clamp time was 21.4+/-8.0 minutes. These patients were divided into 5 groups based on the CVP: group A: 0-1 mmHg; B: 1.1-2 mmHg; C: 2.1-3 mmHg; D: 3.1-4 mmHg and E: 4.1-5 mmHg. The blood loss per transection area during hepatic parenchymal transection and the arterial blood gas before and after liver transection were analyzed. RESULTS: With active fluid load, a constant SBP ≥90 mmHg which was considered as optimal was maintained in 18.6% in group A (95% CI: 10.8%-26.3%); 39.2% in group B (95% CI: 29.5%-48.9%); 72.2% in group C (95% CI: 63.2%-81.1%); 89.7% in group D (95% CI: 83.6%-95.7%); and 100% in group E (95% CI: 100%-100%). The blood loss per transection area during hepatic parenchymal transection decreased with a decrease in CVP. Compared to groups D and E, blood loss in groups A, B and C was significantly less (analysis of variance test, P<0.05). Compared with the baseline, the blood oxygenation decreased significantly when the CVP was reduced. Base excess and HCO3- in groups A and B were significantly decreased compared with those in groups C, D and E (P<0.05). CONCLUSION: In consideration of blood loss, SBP, base excess and HCO3-, a CVP of 2.1-3 mmHg was optimal in patients undergoing partial hepatectomy for HCC.

Hemodynamics and oxygen transport dynamics during hepatic resection at different central venous pressures in a pig model.

BACKGROUND: Although low central venous pressure (CVP) has been used to minimize blood loss during hepatectomy, the impact of variations of CVP on the rate of blood loss and on the perfusion of end-organs has not been evaluated. This animal study aimed to evaluate the hemodynamics and oxygen transport changes during hepatic resection at different CVP levels. METHODS: Forty-eight anesthetized Bama miniature pigs were divided into 8 groups with CVP during hepatic resection controlled at 0 to <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, and 7 to <8 cmH2O. Intergroup comparisons were made for hemodynamic parameters, oxygen transport dynamics, and the rate of blood loss. RESULTS: The rate of blood loss and the hepatic venous pressure during hepatic resection were almost linearly related to the CVP. A significant drop in the mean arterial pressure, cardiac output, and cardiac index occurred between CVP ≥2 and <2 cmH2O. Oxygen delivery (DO2), oxygen consumption (VO2) and oxygen extraction ratio (ERO2) remained relatively constant between CVPs of 2 to <8 cmH2O. There was a significant drop in DO2 when the CVP was <2 cmH2O. There was also a significant drop in VO2 and ExO2 when the CVP was <1 cmH2O. CONCLUSION: The optimal CVP for hepatic resection is 2 to 3 cmH2O.