BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

Objective To investigate the effect of Gouteng Jiangya Jieyu Perscription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,etc.)modulating the TLR4/NF-кB signaling pathway on the polarization of hippocampal microglia in rats with hypertension complicated with depression(HD)Methods Forty primary hypertensive rats were randomly divided into five groups:the model group,the positive drug group,and the high-,medium-,and low-dose groups of Gouteng Jiangya Jieyu Perscription,with 8 rats in each group;and another 8 SD rats were taken as the control group.The HD model was replicated using 42 days of continuous chronic unpredictable mild stress(CUMS)combined with solitary rearing.The modeling was accompanied by the administration of drugs,including 29.61,14.81,and 7.40 g·kg-1 of Gouteng Jiangya Jieyu Perscription in the high-,medium-,and low-dose groups of Chinese herbal medicine,respectively,and 0.45 mg·kg-1 of Levamlodipine Besylate+1.8 mg·kg-1 of Fluoxetine in the positive group;the volume of the gavage was 10 mL·kg-1,once a day,for 42 consecutive days.The systolic blood pressure of rat tail artery was measured by non-invasive sphygmomanometer before drug administration and in the morning of the last day of each week;the behavioural test of Sucrose Preference Test(SPT)was carried out once in the second week and once in the last week after the start of the modelling;the water maze experiment was carried out after the end of the modelling;the levels of serum inflammatory factor tumor necrosis factor-α(TNF-α),interleukin(IL)1β and IL-10 were determined by ELISA;the pathological changes of rat hippocampal tissue neurons were observed by HE staining and Nissl stain were used to observe the neuronal pathological changes in rat hippocampal tissue;immunofluorescence double staining was used to detect the expressions of microglia M1(CD16)and M2(CD206)types in the hippocampal region;and Western Blot was used to detect the protein expressions of TLR4 and NF-кB p65 in the hippocampal tissue.Results Compared with the control group,the systolic blood pressure in the tail artery of rats in the model group from week 1 to week 6 were all significantly increased(P＜0.01);sucrose preference rate was significantly decreased(P＜0.01);evasion latency was significantly prolonged(P＜0.05,P＜0.01),the number of times of traversing the plateau and the percentage of time spent in the target quadrant were significantly decreased(P＜0.01);the contents of serum TNF-α and IL-1β were significantly increased(P＜0.01),IL-10 content was significantly decreased(P＜0.01);cytosolic nuclei were deeply stained,cytoplasmic solidification and apoptosis were obvious;the fluorescence intensity ratio of CD206/CD16 in hippocampal microglial cells were significantly decreased(P＜0.05);the protein expressions of TLR4 and NF-кB p65 in hippocampal tissues were significantly up-regulated(P＜0.01).Compared with the model group,the systolic blood pressure in the tail artery of rats in the first to sixth weeks of the drug administration group were all significantly reduced(P＜0.01);the sucrose preference rates were all significantly increased(P＜0.05);the contents of serum TNF-α and IL-1β were significantly decreased(P＜0.01),and the content of IL-10 was significantly increased(P＜0.01);the Nissl substances are abundant and apoptosis is significantly reduced,and apoptosis were significantly reduced.The escape latency of rats in the positive drug group and the high-dose group of Gouteng Jiangya Jieyu Perscription was significantly shortened(P＜0.05,P＜0.01),and the number of times of crossing the plateau and the percentage of time spent in the target quadrant were significantly increased(P＜0.05);the ratio of fluorescence intensity of hippocampal microglial cells,CD206/CD16 was significantly increased(P＜0.05,P＜0.01);and the hippocampal tissues,protein expressions of TLR4 and NF-κB p65 were significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Perscription may regulate the polarisation state of hippocampal microglial cells,modulate the secretion of inflammatory factors,and attenuate the damage of hippocampal neurons in HD rats by inhibiting the TLR4/NF-кB pathway.

Objective:To evaluate the efficacy and safety of unilateral adrenalectomy for treating primary bilateral macronodular adrenal hyperplasia (PBMAH) of different clinical types.Methods:The clinical and biochemical data of 54 patients with PBMAH who underwent unilateral adrenalectomy from May 2008 to March 2023 were retrospectively collected. Preoperative CT images of all patients showed enlarged bilateral adrenal glands with multiple nodules of " fused masses". Mean preoperative blood cortisol concentration at 8am was (21.5±7.7)μg/dl, urinary free cortisol concentration was (442.6±300.4)μg/24h, and mean 8am ACTH concentration was (6.4±2.3)pg/ml. Postoperative symptoms, BMI, blood pressure, mass diameter, cortisol and ACTH concentration were recorded and analyzed.Results:Compared with ordinary laparoscopic surgery, robot-assisted surgery showed shorter operation time [(115.4±22.1)min vs.(95.0±19.8)min, P=0.045]; less blood loss [(118.2±57.0)ml vs. (125.6±45.3)ml, P=0.441] and shorter hospitalization time [(5.2±0.9)day vs. (6.4±1.2)day, P=0.279]. Compared with laparoscopic surgery, open surgery showed longer operation time [(134 34.5) min vs. (104.3±20.1) min, P=0.035]; more blood loss [(305.5±85.2) ml vs. (122.5±44.3) ml, P=0.012] and longer hospitalization time[(10.4±3.2)day vs. (5.7±1.0) day, P=0.020]. The average follow-up time was (23.7±11.7) months. Sixteen cases biochemically relapsed, and the average relapse-free time was (25.4±13.4) month. Mean postoperative systolic blood pressure was (131.1±16.8)mmHg ( P=0.001) while diastolic blood pressure decreased to (82.2±11.1)mmHg ( P=0.002). Postsurgical average blood cortisol concentration decreased to (10.2±4.0)μg/dl ( P<0.01), while urine cortisol concentration decreased to (106.6±43.4)μg/24h( P<0.01). Average ACTH concentration increased to (12.6±4.1)pg/ml( P=0.005). Recurrent patients had higher preoperative blood and urine cortisol concentration(24.7±8.2)μg/dl( P=0.046), (522.8±234.2)μg/24h( P=0.028), and all of them underwent contralateral adrenalectomy. Conclusions:Unilateral adrenalectomy is safe and effective for treatment of PBMAH while part of patients biochemically relapsed. Subclinical patients were observed no recurrent cases after surgery. Recurrent patients have higher preoperative blood and urine cortisol levels and should undertake contralateral adrenalectomy and supplement corticosteroids for whole life.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the clinical efficacy of 595-nm pulsed dye laser (PDL) in the treatment of port-wine stains (PWS) in infants and toddlers.Methods:A retrospective analysis was conducted based on clinical data from 155 infants and toddlers with PWS treated with 595-nm PDL at West China Hospital of Sichuan University from January 2013 to October 2023, and the efficacy was evaluated according to pre- and post-treatment photographs. The children were grouped according to gender, age, lesion color, lesion area, lesion sites, and number of treatment sessions, separately, and the differences were analyzed between different groups. Further analysis was conducted to determine factors affecting efficacy of PDL for PWS. Adverse reactions after treatment were recorded. The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze unidirectional ordered R × C contingency table data, the Bonferroni approach was used for multiple comparisons, and multivariate ordered logistic regression analysis was performed for multifactorial analysis. Results:After the treatment with 595-nm PDL, 135 infants and toddlers with PWS showed good response, with an overall response rate of 87.1%. Univariate analysis indicated that the efficacy was associated with the lesion area ( P = 0.016) and the number of treatment sessions ( P < 0.001), but not with age ( P = 0.340), gender ( P = 0.164), lesion color ( P = 0.530), or lesion sites ( P = 0.077), and the smaller the lesion area, the more the treatment sessions, the better the therapeutic effect. Multivariate ordered logistic regression analysis further confirmed the correlations of efficacy with lesion area ( P = 0.010) and number of treatment sessions ( P < 0.001). Adverse reactions occurred in 5 (3.2%) cases of PWS, including 2 (1.3%) of hypopigmentation, 2 (1.3%) of hyperpigmentation, and 1 (0.6%) of scar formation. Conclusion:The 595-nm PDL was safe and effective for the treatment of PWS in infants and toddlers with few adverse reactions, making it a reliable therapeutic option.

Objective To study the effects of Gouteng Jiangya Jieyu Prescription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on learning and memory ability,hippocampal inflammatory response and autophagy-related protein expression in rats with hypertension complicated with depression(HD).Methods Thirty spontaneously hypertensive rats(SHR)were randomly divided into model group,positive control group(Levamlodipine Besylate 0.45 mg·kg-1+Fluoxetine Hydrochloride 1.80 mg·kg-1)and Gouteng Jiangya Jieyu Prescription high-,medium-and low-dose groups(25.38,12.69,6.34 g·kg-1).Another 6 SD rats were used as blank control group.The SHR rats were intervened by chronic mild unpredictable stress combined with solitary rearing to replicate the HD rat model.At the same time,intragastric administration was given once a day for 6 weeks.The systolic blood pressure and diastolic blood pressure of rat tail artery were measured by non-invasive sphygmomanometer.The learning and memory ability of rats was detected by Morris water maze test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope.The contents of interleukin-1β(IL-1β),IL-18 and IL-10 in hippocampus were detected by ELISA.The expression of autophagy-related proteins Beclin1 and Bcl-2 in hippocampus was detected by immunohistochemistry.The expression of autophagy-related proteins LC3Ⅰ and LC3Ⅱ in hippocampus was detected by Western Blot.Results Compared with the blank control group,the SBP and DBP of the rats in the model group were significantly increased from week 1-6(P＜0.01).The escape latency was significantly prolonged on the third and fourth day(P＜0.01).The first time of crossing the platform was significantly prolonged(P＜0.01),the times of crossing the platform area was significantly reduced(P＜0.05),and the retention time of the platform area was significantly shortened(P＜0.01).The neuronal cell body was obviously swollen,the ridge was destroyed,the nucleus was shrunk,and a large number of autophagosomes appeared;the contents of IL-1β and IL-18 in hippocampus were significantly increased(P＜0.01).The ratio of LC3Ⅱ/LC3Ⅰ protein expression and the expression of Beclin1 protein in hippocampus were significantly up-regulated(P＜0.05,P＜0.01),and the expression of Bcl-2 protein was significantly down-regulated(P＜0.01).Compared with the model group,the SBP of rats in the low-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at the weeks 1,3,4,5,6(P＜0.01),and the DBP was significantly decreased at weeks 1,3,4,5(P＜0.05,P＜0.01).The SBP of the rats in the medium-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at weeks 1,5,6(P＜0.01),and the DBP was significantly decreased at week 4(P＜0.05).The SBP of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased in the first week(P＜0.01).The escape latency of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the third day(P＜0.05),and the escape latency of rats in the high-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the fourth day(P＜0.05).The first crossing platform time of rats in the high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened(P＜0.01).The times of rats crossing the platform area in the medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription were significantly increased(P＜0.05),and the retention time in the platform area was significantly prolonged(P＜0.05).In the administration group,the degree of hippocampal neuron damage was reduced,the nuclear shrinkage was significantly improved,and the autophagosomes were reduced.The contents of pro-inflammatory factors IL-1β and IL-18 in the hippocampus of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription were significantly decreased(P＜0.05,P＜0.01).The content of anti-inflammatory factor IL-10 in the hippocampus of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly increased(P＜0.01).The protein expression ratio of LC3Ⅱ/LC3Ⅰ in hippocampus of high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.01),and the expression of Bcl-2 protein was significantly up-regulated(P＜0.01).The expression of Beclin1 protein in the hippocampus of the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Prescription can reduce the tail arterial pressure of HD rats,improve their learning and memory ability,and alleviate hippocampal neuronal damage.The mechanism may be related to reducing the release of inflammatory factors,increasing the level of anti-inflammatory factors,and regulating the expression of hippocampal autophagy-related proteins LC3Ⅱ/LC3Ⅰ,Beclin1 and Bcl-2.

Objective:To explore the causal relationship between body mass index (BMI) and hypothyroidism using the two-sample Mendelian randomization model.Methods:A large-scale anthropometric genome-wide association study published in the GIANT database was used to select single nucleotide polymorphisms (SNPs) which were statistically significantly associated with BMI as an instrumental variable ( P<5×10 -8, linkage disequilibrium r 2<0.1). The causal relationship between BMI and hypothyroidism was determined by the inverse variance weighted (IVW), weighted median method and the MR-Egger method, respectively. A heterogeneity test, gene pleiotropy test, and sensitivity analysis were performed to evaluate the stability and reliability of the results. Results:A total of 89 SNPs related to BMI were screened out as instrumental variables. IVW analysis suggested that for every standard deviation increase in BMI, the risk of hypothyroidism increased by 0.9% (odd ratio ( OR)=1.009, 95% confidence interval ( CI): 1.006-1.012, P<0.001). Similar results were obtained with the weighted median method ( OR=1.007, 95% CI: 1.002-1.011, P=0.003) and the MR-Egger method ( OR=1.008, 95% CI: 1.001-1.015, P=0.006). The MR-Egger analysis showed that genetic pleiotropy did not bias the results (intercept=0.000 1, P=0.776), the one-by-one exclusion method did not show that a single instrumental variable SNP had a significant impact on the results, and the difference was not statistically significant ( P>0.05). Conclusion:Mendelian randomized analysis showed a positive causal relationship between BMI and hypothyroidism.

Objective To explore the regulatory effect of Mertk expression level on NF-κb pathway in rat Schwann cells and its possible mechanism.Methods Rat Schwann cells were cultured in vitro,and the expression of Mertk in Schwann cells exposed to high glucose was detected by Western blot.Co-immunoprecipitation was used to detect the interaction between endogenous Mertk and Ikbkb.Western blot was used to detect the expression levels of Ikbkb,P65 and tumor necrosis factor-α in Schwann cells after Mertk silencing.The protein expressions of Mertk,Ikbkb and P65 after silencing Mertk were detected by immunofluorescence.Results Mertk was expressed in Schwann cells,and the expression level increased with the increase of glucose concentration.Co-immunoprecipitation assay showed that Mertk interacted with Ikbkb in rat Schwann cells.Compared with the control group,the expression level of Mertk was significantly decreased(P<0.05),while Ikbkb,P65 and TNF-α were significantly increased(P<0.05)after knock down expression of Mertk in Schwann cells.Immunofluorescence experiments showed that the fluorescence of Mertk was decreased,and the fluorescence of Ikbkb and P65 was increased in the silenced Schwann cells.Conclusion After the expression of Mertk is decreased,it can mediate the regulation of NF-κb pathway in Schwann cells through interaction with Ikbkb,and up-regulate the expression of P65 and inflammatory factor TNF-α.

Objective:To explore the effect of intraspinal labor analgesia on labor progress, maternal and infant outcomes.Methods:Two hundred cases of full-term singleton primiparous women in head position admitted to the Second Affiliated Hospital of Shantou University Medical College from March 2019 to March 2020 were selected as the research subjects. According to the random number table method, they were divided into the control group (100 cases, natural delivery) and the analgesia group (100 cases, analgesia delivery). The visual analoguescore (VAS), progress of labor, and the outcome of delivery between the two groups werecompared.Results:The VAS scores of the analgesic group at 10, 30 and 60 min after analgesia were lower than those in the control group: (1.30 ± 0.17) scores vs. (9.50 ± 0.53) scores, (0.50 ± 0.22) scores vs. (9.50 ± 0.16) scores, (0.40 ± 0.28) scores vs. (9.50 ± 0.34) scores, the differences were statistically significant ( P<0.05). The first stage of labor in the analgesia group was longer than that in the control group: (347.6 ± 54.4) min vs. (325.8 ± 58.5) min; but the active stage, the second stage of labor, the third stage of labor and the total duration of labor in the analgesia group were shorter than those in the control group: (184.3 ± 39.5) min vs. (202.9 ± 42.7) min, (57.8 ± 17.9) min vs. (85.3 ± 16.9) min, (7.7 ± 5.0) min vs. (16.3 ± 5.2) min, (503.6 ± 131.4) min vs. (596.5 ± 175.7) min, the differences were statistically significant ( P<0.05). The 2 h and 24 h postpartum hemorrhage in the analgesia group were significantly lower than those in the control group: (223.64 ± 80.34) ml vs. (276.97 ± 82.35) ml, (331.57 ± 92.47) ml vs. (384.59 ± 94.25) ml, the differences were statistically significant ( P<0.05). The rate of normal delivery and the use of oxytocin in the analgesia group were higher than those in the control group: 91.0%(91/100) vs. 75.0%(75/100), 83.0%(83/100) vs. 49.0% (49/100), the differences were statistically significant ( P<0.05). In the newborn Apgar scores, the muscle tension, pulse, reflex response, respiration score and total score in the analgesia group were significantly higher than those in the control group ( P<0.05). The neonatal distress in the analgesia group was lower than that in the control group: 4.0%(4/100) vs. 15.0%(15/100), the difference was statistically significant ( P<0.05). Conclusions:Intravertebral labor analgesia can shorten the time of parturient delivery, reduce postpartum hemorrhage, improve the Apgar score of newborns, increase the pregnancy rate, and improve maternal and infant outcome.