Objective To evaluate the effect of dexmedetomidine on spinal p38 mitogen?activated protein kinase ( p38MAPK) expression during remifentanil?induced hyperalgesia in rats with incisional pain. Methods Forty?eight healthy male Sprague?Dawley rats, aged 6 weeks, weighing 220-250 g, were ran?domly divided into 4 groups ( n= 12 each) using a random number table: control group ( group C) , inci?sion pain group ( group IP ) , incision pain + remifentanil group ( group IP+R ) , and incision pain +remifentanil + dexmedetomidine group ( group IP+R+D) . After successful establishment of the model of in?cisionsal pian, remifentanil 1?0μg∕kg was infused for 4 h via the tail vein in group IP+R; remifentanil 1?0μg∕kg was infused for 4 h via the tail vein, and dexmedetomidine 10μg∕kg was simultaneously infused for 4 h via the jugular vein in group IP+R+D; the equal volume of normal saline was infused for 4 h via the tail and jugular veins in C and IP groups. The mechanical paw withdrawal threshold ( MWT) was measured at 24 h before operation ( T0 ) , and at 4, 6, 24 and 48 h after the end of drug infusion ( T1?4 ) . After meas?urement of MWT at T4 , the expression of p38MAPK was determined using immuno?histochemistry. Results was up?regulated at T4 in IP and IP+R groups ( P<0?05) , and no significant change was found in the MWT and expression of p38MAPK in group IP+R+D (P>0?05). Compared with group IP, the MWT was signifi?cantly decreased at T1?4, and the expression of p38MAPK was up?regulated at T4 in group P+R, and the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D (P<0?05). Compared with group IP+R, the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D ( P<0?05) . Conclusion The mecha?nism by which dexmedetomidine reduces hyperalgesia induced by remifentanil is related to down?regulation of spinal p38MAPK expression in the rats with incisional pain.

Objective:To compare the advantages and disadvantages of thoracic paravertebral nerve block combined with new nasopharyngeal airway preserved spontaneous breathing anesthesia and traditional double-lumen bronchial intubation combined with general anesthesia for thoracoscopic surgery.Methods:A total of 48 patients with thoracoscopic surgery admitted to the department of thoracic surgery, Hunan Provincial People′s Hospital from January 2020 to May 2022 were selected and divided into two groups by random number table method, with 24 cases in each group. The observation group was treated with thoracic paravertebral nerve block combined with a new type of nasopharyngeal airway to retain spontaneous breathing; The control group was treated with traditional double-lumen bronchial intubation combined with general anesthesia. The sedation and analgesia scores, perioperative plasma cortisol, norepinephrine and epinephrine levels, hemodynamic indexes, intraoperative opioid dosage at different time points (T0 after intubation or nerve block, skin incision T1, artificial pneumothorax T2, focus resection T3, and chest closure T4), as well as early out of bed activity and length of stay in hospital after operation were compared between the two groups.Results:The sedation scores of the observation group at T0, T1, T2, T3, T4 were significantly higher than those of the control group (all P<0.05); The analgesic scores at T2, T3 and T4 in the observation group were significantly lower than those in the control group (all P<0.05). The plasma cortisol and epinephrine levels at T0, T1, T2, T3, T4 in the observation group were lower than those in the control group, and the difference was statistically significant (all P<0.05); The levels of norepinephrine at T1, T2, T3 and T4 in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in heart rate at T1 between the observation group and the control group ( P>0.05), but the heart rate at T0, T2, T3, T4 was lower than that in the control group (all P<0.05). The mean arterial pressure at each time point in the observation group was lower than that in the control group, with statistically significant difference (all P<0.05). The total amount of opioid in the observation group was significantly less than that in the control group ( P<0.05). The Visual Analogue Scale (VAS) scores of rest and exercise in the observation group were significantly lower than those in the control group (all P<0.05). The time of getting out of bed , standing, walking, anus exhaust and blowing out the lighter in the observation group were significantly shorter than those in the control group (all P<0.05). The times of nausea and vomiting, patient controlled intravenous analgesia (PCIA) pressing and hospitalization in the observation group were significantly less than those in the control group (all P<0.05). Conclusions:Thoracic paravertebral nerve block combined with new nasopharyngeal airway to preserve spontaneous breathing " tubeless" anesthesia can provide better sedation and analgesia effect and lower perioperative stress level than traditional double-lumen bronchial intubation combined with intravenous inhalation general anesthesia. It also has obvious advantages in rapid recovery after surgery.

Ischemia reperfusion injury (IRI) of organs is a major challenge for clinicians, but the mechanism is still not elucidated, and the clinical treatment effect is still unsatisfactory. PARP-1-dependent cell death (parthanatos) is a non-apototic programmed cell death pathway involved in the development of the occurrence of IRI of organs. At the same time, parthanatos is also a multi-step pathway. There are many molecules in the parthanatos cascade that can be exploited to create therapeutic interventions for IRI, including PARP1, apoptosis inducing factor (AIF), and macrophage migration inhibitory factor (MIF). These critical molecules are involved in DNA damage, energy depletion and homeostasis imbalance. Therefore, these molecular signals in the parthanatos cascade represent promising therapeutic targets for the treatment of IRI. In the following, we will elaborate on the mechanisms and molecular characteristics of the parthanatos pathway and the relation between parthanatos pathway and IRI of vital organs. It aims to explore the posibility of IRI mechanism research and clinical treatment and to provide new ideas for clinicians and researchers.

OBJECTIVE:To study the effects of Dianxianqing granule on the interleukin(IL-6)content and glial fibrillary acid-ic protein(GFAP),ionized calcium linker molecules 1(Iba-1)expressions in hippocampus tissue of rats with kainate-induced epi-lepsy,and explore its mechanism of preventing and treating epilepsy. METHODS:Rats were randomly divided into sham operation group (distilled water),model group (distilled water),phenytoin group (0.03 g/kg,positive control) and Dianxianqing granule low-dose,medium-dose,high-dose groups(4.74,9.47,18.94 g/kg,calculated by crude drug),20 in each group. Rats were intra-gastrically administrated once a day,for 7 d. After 1 h of last administration,except for sham operation group,rats in other groups received single injection of kainite in hippocampus CA1 of left side to induce the epilepsy model. Behavioral changes and death of rats were observed. After 24 h of modeling,enzyme-linked immunosorbent method was used to detect the IL-6 content in hippocam-pus tissue of rats,Nissl staining was used to count the hippocampus neurons,and immunohistochemistry was used to detect the GFAP,Iba-1 expressions in hippocampus tissue of rats. RESULTS:Compared with sham operation group,rats in model group had obvious epilepsy symptoms after modeling,and parts of rats died;IL-6 content and number of neurons in hippocampus tissue were obviously decreased (P<0.01), while GFAP, Iba-1 expressions were obviously enhanced (P<0.01). Compared with model group,epilepsy symptoms and death in each administration group had improved,while IL-6 content in hippocampus tissue were in-creased to varying degrees,with no statistical significance (P>0.05). The numbers of neurons in phenytoin group,Dianxianqinggranule medium-dose, high-dose groups were obviously in-creased(P<0.01);GFAP expression was obviously decreased (P<0.01). Iba-1 expressions in hippocampus tissue in phenyt-oin group,Dianxianqing granule high-dose group were obvi-ously decreased (P<0.01). CONCLUSIONS:Dianxianqing granule can play the role in preventing and treating epilepsy by inhibiting GFAP,Iba-1 expressions in hippocampus tissue and in-creasing the number of neurons in hippocampus tissue.

The data of a patient with autosomal dominant optic atrophy (ADOA) and chronic renal insufficiency caused by SSBP1 gene mutation in the Children′s Hospital Affiliated to Zhengzhou University in July 2021 was analyzed retrospectively.Literature was reviewed.The patient was a 10-year-old girl, who visited the hospital due to " growth retardation for the past 3 years and elevated serum creatinine (Scr) for the past 2 years" . On admission, the patient′s height was 130 cm (<10 th percentile of the same sex of healthy age) and her weight was 22 kg (<3 rd precentile of the same sex of healthy age). Lab examination showed that the level of blood urea nitrogen (BUN) was 16.3 mmol/L, Scr was 115.4 μmol/L, and the estimated glomerular filtration rate was 41 mL/(min·1.73 m 2). The patient was complicated with metabolic acidosis and mild anemia.Imaging findings showed small volume of both kidneys, increased background parenchymal enhancement, scattered spot-like hyperechoes and unclear boundary between the cortex and medulla.Additionally, the patient had a history of optic atrophy.Both the father and mother of the patient had no related phenotypes.The genetic test of the patient showed that c. 320G>A (p.R107Q) was a heterozygous missense mutation, which was spontaneous.A total of 5 English papers were retrieved.There were 8 kinds of SSBP1 gene mutations reported, including 7 heterozygous missense mutations [c.320G>A (p.Arg107Gln), c.119G>T (p.Gly40Val), c.331G>C (p.Glu111Gln), c.184A>G (p.Asn62Asp), c.113G>A (p.Arg38Gln), c.422G>A (p.Ser141Asn), c.79G>A (p.Glu27Lys)] and 1 homozygous mutation [c.394A>G (p.Ile132Val)]. Studies have established that almost all patients carrying SSBP1 mutations have manifestations of eye involvement, and that some patients are complicated with progressive deterioration of renal function, sensorineural deafness, growth retardation, and hypothyroidism.It suggests that SSBP1 gene mutation can cause ADOA.For patients with optic atrophy, whether they are complicated with hearing loss and growth retardation, renal morphology and renal function evaluation are recommended.Early genetic examination is helpful for diagnosis and treatment.

Objective:To summarize the clinical and genetic characteristics, treatment and prognosis of four children with Steroid-resistant nephrotic syndrome (SRNS) due to variants of TRPC6 gene. Methods:Clinical data of four children with SRNS admitted to Children′s Hospital Affiliated to Zhengzhou University between May 2020 and August 2022 were collected. Peripheral blood samples were collected from the children and their parents, and whole exome sequencing was carried out. Sanger sequencing was used to verify the pathogenicity of the candidate variants among the children and their parents.Results:All of the four children were found to harbor heterozygous variants of the TRPC6 gene, including c. 523C>T (p.R175W), c. 1327T>A (p.F443I), c. 430G>C (p.E144Q) (unreported previously), and c. 523C>T (p.R175W), which were all missense variants. Two of the children have shown a simple type, whilst two have shown a nephritis type, none had extrarenal phenotype. Comprehensive renal pathology of three children revealed focal segmental glomerulosclerosis (FSGS). Two children were treated with steroids combined with calcineurin inhibitors (CNIs), among whom one showed significant improvement in symptoms. Conclusion:Discoveries of the novel c. 430G>C variant and the new SRNS phenotype of the c. 1327T>A variant have expanded the mutational and phenotypic spectrum of the TRPC6 gene, which has provided a reference for clinical diagnosis and genetic counseling for the families.

Objective:To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome.Methods:This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children′s Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19 +B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results:There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20) vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation ( OR=0.26, 95% CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95% CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×10 6/L. Conclusions:The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×10 6/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.

Transient receptor potential cation channel 6（TRPC6）gene is mainly expressed in renal podiocytes.Its variation can lead to steroid-resistant nephrotic syndrome（SRNS），and the specific pathogenesis is not clear.These children have poor response to hormones and immunosuppressants，with lack of specific therapeutic drugs，and poor prognosis.In recent years，it has been found that some drugs can slow down disease progression by inhibiting the expression of TRPC6 gene or its downstream signaling pathway，and the discovery of TRPC6 protein-specific blockers may be the hope of treating such children.This review focuses on the pathogenesis of SRNS induced by TRPC6 gene variation in children and the research progress of drug therapy.

To observe the safety and impact on the short-term prognosis for patients of stroke volume variation (SVV) goal-directed fluid therapy (GDFT) in laparoscopic precision hepatectomy.
 Methods: A total of 120 patients (18-65 years old) undergoing laparoscopic precision hepatectomy were randomly divided into the fluid therapy group (group S) guided by SVV and the fluid therapy group (group C) guided by central venous pressure group (CVP), with 60 cases in each group. Mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time: at home calm (T0), the operation started (T1), began to cut the liver (T2), the hepatectomy was acheived (T3), and in the end (T4). The lactic acid was measured at T0 to T4 and 1 day after surgery (T5). The amount of blood loss, urine output and fluid supplement, the incidence of intraoperative hypotension, and the use of neophryn were recorded. The recovery of liver function, Hb, and so on were also recorded.
 Results: Compared with the group C, the number of hypotension cases, the amount of blood loss and the amount of neophryn in the group S were decreased during the operation (P<0.05), while the lactic acid values in the group S were not significantly increased than those in the group C at T3 and T4 (P<0.05) and the elevation of AST, ALT, DBIL and TBIL in the group S was significantly decreased than those in the group C at 1 and 2 d after the operation (P<0.05). Hb and Hct in the group S were higher than those in the group C at 1 d after the surgery (P<0.05). Compared with the group C, the postoperative exhaust time and hospitalization time were shortened in the group S (P<0.05), and the infection rate and ICU admission rate were decreased in the group S (P<0.05).
 Conclusion: SVV-guided GDFT in laparoscopic precise hepatectomy is safe and effective. It reduces intraoperative blood loss and benefits the short-term prognosis of patients after operations. High SVV value (13%-17%) is adopted at the liver resection stage, and SVV value with 8%-12% at the end of trans-section may be used as one of intraoperative liquid therapy in laparoscopic precise hepatectomy.
Adolescent ; Adult ; Aged ; Central Venous Pressure ; Fluid Therapy ; Hepatectomy ; Humans ; Laparoscopy ; Middle Aged ; Stroke Volume ; Young Adult