Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

This report describs 2 domestic cases of tacrolimus poisoning in kidney transplant recipients due to overexposure of tacrolimus caused by nirmatrelvir/ritonavir for SARS-CoV-2 infection.Phenytoin sodium is prescribed for inducing CYP3A enzyme.It is intended for providing references for formulating and adjusting treatment protocols for tacrolimus overexposure and related toxicity in kidney transplant recipients caused by nirmatrelvir/ritonavir.

Objective:To explore the safety and effectiveness of medium-frequency electrotherapy for increasing the volume of the latissimus dorsi muscle.Methods:Fifteen adult New Zealand white rabbits were randomly divided into three groups, namely group A, group B, and group C, with 5 rabbits in each group. This was a self-control study, with the right latissimus dorsi muscle as the experimental group and the left latissimus dorsi muscle as the control group. The three groups corresponded to three different current intensity levels: 7.062 mA for group A (6th gear), 10.593 mA for group B (9th gear), and 14.124 mA for group C (12th gear). After the 12th, 24th, and 36th sessions of the experiment, ultrasonography was used to collect the thickness of the latissimus dorsi muscle. After the 36th electrostimulation, the latissimus dorsi muscle samples were collected to measure their in vivo muscle thickness and wet weight and were then sent for HE and MASSON staining.Results:After the 12th, 24th, and 36th electrostimulation sessions, ultrasonographic sampling in groups A and B showed an increase in the thickness of the right latissimus dorsi muscle compared to the left; for example, the thickness on the right of group B increased by 37.8%. The wet weight data collected after the 36th electrostimulation in groups A and B showed an increase in the right latissimus dorsi muscle compared to the left; for example, the wet weight on the right of group B increased by 5.04%.Conclusions:Different electrostimulation modes of medium-frequency therapy technology can induce muscle fiber thickening or atrophy. In this experiment, the 9th gear (10.593 mA) of medium-frequency therapy technology may be a suitable choice for inducing muscle fiber thickening, and the 12th gear (14.124 mA) may be a suitable choice for inducing skeletal muscle thinning.

Objective To retrospectively analyze the injury characteristics of victims and treatment strategies in the explosion accident on the 17th May 2018 in Xixia county (Xixia "May 17th" explosion accident). Methods Based on the practice featured in pre-hospital emergency of Henan province and Nanyang city Emergency Center in the explosion accident, a retrospective analysis for the Level Three medical rescue was conducted, where a total of thirteen survived victims in Xixia "May 17" explosion accident were studied retrospectively. The data included the gender, age, burned extent and depth of the patients, burns complicated by trauma, complication of burn, respiratory function maintenance, resuscitation during shock stage, skin grafting with excision and scab. Furthermore, the data of organ function and the effect of the 90-day comprehensive treatment for the burned victims wereanalyzed. Results completion the Level Three treatment on time, which was depended on the leading role played by the regional trauma centers was the main rescuing mode of the work in Xixia county, where the primary and secondary treatments were the key parts. The three-level treatment model includes: the local hospital acts as a level-one emergency medical institution, county hospitals function as secondary emergency medical institutions, and other higher medical institutions are the tertiary first aid medical institutions. The pre-hospital and in-hospital emergency procedures were initiated immediately after the large-scale explosive burn being identified, the key to the successfully rescue was to set up a comprehensive treatment team for burns and trauma. Rescue team should involve burn department and other related departments, including the departments of emergency, general surgery, orthopedic, thoracic surgery, neurosurgery, plastic surgery, intensive care unit, blood transfusion unit, anesthesiology, and interventional radiology, etc. All the thirteen burned patients were male, with inhalation injury, blast injury, hemopneumothorax, brain injury, bone fractures, and etc. Eight of them (61.54%) had multiple organ dysfunction syndrome (MODS). MODS mainly involved respiratory, circulatory, liver, gastrointestinal tract, kidney and coagulation function. With the multi-discipline treatment, the wound of 6 severely-burned patients started healing and can be discharged after keeping the patency of airway, applying resuscitation fluid and comprehensive treatments such as debridement and dressing change. Among 7 patients with extensive deep burns, one case with skull-based fracture, open craniocerebral, extensive intracranial hemorrhage and hemopneumothorax, died 9 hours later. Another case died within 24 hours after injury due to obvious exudation on the site of early incision and relaxation of wound. The escharotomy, micro-dermis and allograft skin transplantation were carried out for five cases with extensive deep burns from the 4th day after the recovery of shock. One week later, the second stage of microsphere skin transplantation was performed. But all died of sepsis or fungal infection. Conclusions MODS and infection often occur during the course especially for patients with extensive and deep burns due to the great explosion in Xixia county, most of whom were accompanied with MODS and infection. Therefore, assembling multi-discipline team for treating the group of explosively-burned patients can increase the survival rate and reduce the possibility of disability.

Objective To explore the relationship between positive cervical lymph nodes and distant metastasis after intensity-modulated radiotherapy(IMRT)in patients with nasopharyngeal carcinoma(NPC). Methods A retrospective analysis was performed on the clinical data of 474 patients who were newly diagnosed with NPC but no distant metastasis and received IMRT from 2010 to 2012. The survival rates were calculated by the Kaplan-Meier method. The log-rank test was used for comparison of survival rates and univariate prognostic analysis. The multivariate analysis was made by the Cox regression model. Results In the 474 patients, 400 had positive cervical lymph nodes and 122 had residual masses in the neck after IMRT. The four-year distant metastasis, overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival(DMFS)rates were 13.71%(65/474), 82.9%, 81.4%, 93.5%, and 86.3%, respectively. The univariate and multivariate analyses showed that treatment approach, lymph node metastases in lower neck Ⅳ/Ⅴb/Ⅴcregions, the greatest diameter of the positive cervical lymph nodes, the diameter of residual lymph nodes, and time to lymph node recession were independent prognostic factors for DMFS(all P<0.05). Conclusions Chemoradiotherapy can reduce the distant metastasis rate after IMRT for NPC. The larger the cervical lymph nodes are,the more likely there are residual masses;the larger the residual cervical lymph nodes are, the higher risk of distant metastasis there is. Large cervical lymph nodes(≥6 cm),residual masses larger than 1 cm,and residual masses at 3 months after IMRT are negative prognostic factors for DMFS after IMRT for NPC. Better intervention treatment approaches need to be explored.

Resident standardization training is an important part of postgraduate medical educa-tion and anesthesiology rotation is an important part in resident standardization training. Anesthesiology rotation is an effective way to improve the efficiency of hospital operation and is an important starting point to promote 'comfortable medical' and hospital upgrades. To improving the quality of training , anes-thesiology department should establish training and supervision system clearly , organize teacher training regularly. Continuous improvements in institutional mechanism can be achieved by detailed theoretical studies, technical operations and departmental rotation examination requirements as well as by exchanging ideas between teachers and students.

Objective To investigate the protective effect of a COX inhibitor,flurbiprofen (Flurb) on hepatic ischemia/reperfusion (IR) injury in rats and the action mechanism.Method C57BL/6 mice were randomized into sham,IR and Flurb (4 different doses) groups.The model of segmental (70％) warm hepatic ischemia was established in IR and Flurb groups.Flurbiprofen of different doses (5,7.5,10 and 15 mg/kg) was injected via the tail vein 20 min before ischemia.At different time points after reperfusion,liver cell necrosis and apoptosis were evaluated by HE and TUNEL staining.The COX and inflammatory cytokine gene expression was detected by using realtime PCR.Liver mitochondria were separated and mitochondrial permeability transition (MPT) pore sensitivity was examined by using swelling assay and fluorescence spectrophotometry assay.Result In flurbiprofen groups of different doses,the serum AST and ALT levels were significantly decreased at 6 h after reperfusion as compared with IR group.Moreover,10 mg/kg Flurb pretreatment significantly inhibited the mitochondrial permeability transition (MPT) pore opening,and thus alleviated liver cell damage and prevented mitochondria-related cell death and apoptosis by inhibiting COX-2 and inflammatory factor genes expression such as IL-1β,IL-6 and TNF-α.Conclusion Flurbiprofen protects mice from hepatic I/R injury possibly by inhibiting mitochondrial permeability transition and IL-1β,IL-6 and TNF-α expression,which may provide experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings other than its conventional use for pain relief.

Objective To investigate the cerebral protective effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody (1A29) in rats with global cerebral ischemia/reperfusion (I/R) injury. Methods Forty healthy SD rats weighing 180-200 g were randomly divided into 4 groups ( n = 10 each) : group Ⅰ received isotype-matched control antibody 1 mg/kg iv (control group); group Ⅰ ,Ⅲ ,Ⅳ received 1A29 1 mg/kg iv before cerebral ischemia (group Ⅱ), at the onset of reperfusion (group Ⅲ) and at 4 h of reperfusion (group Ⅳ) respectively. The global cerebral I/R was produced by 30 min four-vessel occlusion followed by 24 h reperfusion. All animals were killed at 24 h of reperfusion. Their brains were removed for microscopic examination and measurement of W/D weight ratio, infarct size and neurological deficits (0 = no deficit,4 = unable to crawl with mental depression) .Results The PMN leukocyte and monocyte infiltration, water content of the brain and infarct size were significantly decreased in group Ⅱ ,Ⅲ and Ⅳ as compared with control group. The neurological deficit scores were significantly lower in group Ⅱ ,Ⅲ, Ⅳ(1.6-1.8) than in control group (2.5).Conclusion 1A29 antibody administered either before ischemia or during the 4 h of reperfusion can protect the brain against global cerebral I/R injury.

Objective To investigate the effect of propofol pretreatment on hypoxia-induced apoptosis of alveolar epithelial type Ⅱ (AE Ⅱ) cells in fetal rats. Methods Primary cultured AE Ⅱ cells isolated from fetal rats were seeded in 96-well plates (1 × 106/L, 180 μl/well) and randomly assigned to one of 3 groups (n = 72each):normal control group (group C), hypoxia group (group H) and propofol-hypoxia group (group P-H).Group H and P-H were exposed to hypoxia (5% O2). In group P-H, propofol (final concentration 5 μ mol/L) was added 1 h prior to hypoxia (5% O2). The apoptotic rate and expression of hypoxia-inducible factor (HIF)-1αmRNA, Bnip3L mRNA, HIF-1α protein and Bnip3L protein were determined at 3, 12, 24 and 48 h of hypoxia.Results The apoptotic rate and expression of HIF-1α mRNA, Bnip3L mRNA, HIF-lα protein and Bnip3L protein were significantly up-regulated in group H compared with group C (P ＜ 0.05). Propofol pretreatment could significantly inhibit the hypoxia-induced changes mentioned above (P ＜ 0.05). Conclusion Propofol pretreatment can inhibit hypoxia-induced apoptosis of AE Ⅱ cells, and the mechanism is related to inhibition of HIF-1αactivation and down-regulation of Bnip3L expression in fetal rats.

Objective To analysis the causes of cardic arrest during liver transplantation, and investigate the preventive measures. Methods Clinical records about 5 patients with cardiac arrest in liver transplant were studied retrospectively. Results Occurrence of cardiac arrest was 2.1 % (5/240). All the events happened at 3-6 min after graft reperfusion, and arrest lasted 3-8 min. Two patients died of resuscitation failure. After graft reperfusion, CVP and MPAP were much high in 5 patients. All of them had hypothermia and hypocalcemia. Three of them also had acidosis and two complicated with hyperkalemia. In one case, the difference between PaCO_2 and P_ETCO_2 was 47 mm Hg. Conclusion Many factors, such as disturbances of electrolyte and acid-base equilibrium or hypothermia, seemed to have some contribution to cardiac arrest occurrence after reperfusion. Various methods should be used to counter it.