Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

OBJECTIVE: To explore the association between blood glucose trajectories within 7 days of intensive care unit (ICU) admission and mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS). METHODS: Based on the MIMIC-IV database, sepsis-associated ARDS patients with daily blood glucose monitoring data within 7 days of ICU admission were selected. Blood glucose trajectories were analyzed using group-based trajectory modeling (GBTM), and the optimal number of groups was determined based on the minimum Akaike information criterion (AIC), Bayesian information criterion (BIC), average posterior probability (AvePP), odds of correct classification (OCC), and proportion of group membership (Prop). Baseline characteristics including demographics, comorbidities, severity scores, vital signs, laboratory indicators within the first 24 hours of ICU admission, and treatments were collected. Kaplan-Meier survival curves were used to compare 28-day and 1-year survival across trajectory groups. Multivariate Logistic regression was performed to evaluate the associations between glucose trajectory groups and in-hospital mortality, ICU mortality. The incidence of hypoglycemia within 7 days in the ICU was analyzed among different groups. RESULTS: A total of 3 869 patients with sepsis-associated ARDS were included, with a median age of 63.52 (52.13, 73.54) years; 59.6% (2 304/3 869) were male. Based on glucose levels within 7 days, patients were categorized into three groups: persistent hyperglycemia group (glucose maintained at 10.6-13.1 mmol/L, n = 894), moderate glucose group (7.8-8.9 mmol/L, n = 1 452), and low-normal glucose group (6.1-7.0 mmol/L, n = 1 523). There were statistically significant differences in 28-day mortality and 1-year mortality among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [28-day mortality: 11.42% (174/1 523), 19.83% (288/1 452), 25.50% (228/894), χ ² = 82.545, P < 0.001; 1-year mortality: 23.31% (355/1 523), 33.75% (490/1 452), 39.49% (353/894), χ ² = 77.376, P < 0.001]. Kaplan-Meier analysis showed that higher glucose trajectories were associated with significantly lower 28-day and 1-year cumulative survival rates (Log-rank test: χ ² were 83.221 and 85.022, both P < 0.001). There were statistically significant differences in in-hospital mortality and ICU mortality among the low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [in-hospital mortality: 9.65% (147/1 523), 19.70% (286/1 452), 24.50% (219/894), χ ² = 102.020, P < 0.001; ICU mortality: 7.22% (110/1 523), 16.05% (233/1 452), 20.13% (180/894), χ ² = 93.050, P < 0.001]. Logistic regression confirmed that, using the persistent hyperglycemia group as the reference, the low-normal glucose group had significantly lower risks of in-hospital mortality and ICU mortality after multiple factor adjustment. Although the moderate glucose group showed a trend toward lower mortality, the differences were not statistically significant. Using the moderate glucose group as a reference, the low-normal glucose group had 43.1% lower in-hospital mortality [odds ratio (OR) = 0.569, 95% confidence interval (95%CI) was 0.445-0.726, P < 0.001] and 42.0% lower ICU mortality (OR = 0.580, 95%CI was 0.439-0.762, P < 0.001). There was no statistically significant difference in the incidence of hypoglycemia within 7 days of ICU admission among low-normal glucose group, moderate glucose group, and persistent hyperglycemia group [2.82% (43/1 523), 2.69% (39/1 452), 3.02% (27/894), χ ² = 0.226, P = 0.893]. CONCLUSIONS Blood glucose trajectories during ICU stay are closely associated with prognosis in patients with sepsis-associated ARDS. Persistent hyperglycemia (10.6-13.1 mmol/L) is linked to significantly higher short- and long-term mortality.
Humans ; Respiratory Distress Syndrome/etiology* ; Sepsis/blood* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Blood Glucose/metabolism* ; Hospital Mortality ; Aged

In recent years,psoriatic arthritis has become a major problem in the medical field,with cases gradually increasing in China,and it is still incurable.Here,we summarize the pathogenesis and clinical characteristics of currently available animal models of psoriatic arthritis based on Chinese and Western medical evidence.Literature in line with this topic was collated and summarized.The etiology and pathogenesis according to Chinese and Western medicine of existing psoriatic arthritis models were given agreement scores;the diagnostic criteria of Chinese and Western medicine were compared;and the models'characteristics and degree of agreement with clinical observations were assessed.This study found that the human leukocyte antigen transgenic mouse model,the multiple hybridization transgenic mouse model,and the mannan-induced mouse model had the highest agreement scores.As psoriatic arthritis is more common in Europe,methods for the preparation of animal models have been mostly imported from abroad,and very few animal models have the characteristics of Chinese medicine;therefore,the model fitness scores of Western diagnoses were higher than those of Chinese diagnoses as a whole.We hope to leverage the unique diagnosis and treatment method of Chinese medicine further to improve the types of psoriatic arthritis animal models available.This study provides a basis for the construction of improved animal models of psoriatic arthritis with combined traditional Chinese and Western medicine characteristics.

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

OBJECTIVE To study the improvement effects and mechan ism of thalidomide on Alzheimer ’s disease （AD）model of Caenorhabditis elegans . METHODS In this study ，the BR 5270 strain of C. elegans was used as AD model and BR 5271 strain as the control. The effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the motility of BR 5270 strains of C. elegans were studied by the basal slowing response assay ；the effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the survival time of BR 5270 strain of C. elegans were studied by life assay ；the effects of thalidomide （0.5，2.0，6.0 mg/mL）on learning and memory ability of BR 5270 strain of C. elegans were studied by short-term and long-term learning and memory assay. RT-PCR technology was used to study the effects of thalidomide （0.5，2.0，6.0 mg/mL）on mRNA expression of phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）signal pathway related genes （Age-1，Akt-1，Gsk-3）and calpain homologous gene （Clp-1）in BR 5270 strain of C. elegans . RESULTS After the intervention of thalidomide ，oscillation times of BR 5270 strain of C. elegans increased significantly within 30 s （except for 0.5 mg/mL group ），and the 10％ of maximum life span was prolonged significantly （only 0.5 mg/mL group ）；the short-term and long-term learning indexes were improved significantly （only 6.0 mg/mL group ）；mRNA expression of Age-1 and Akt-1（except for 0.5，2.0 mg/mL groups ）were increased significantly ，mRNA expression of Gsk-3（except for 0.5 mg/mL group ） and Clp-1 were decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Thalidomide can ameliorate the dyskinesia of AD model of C. elegans，prolong the lifespan of this strain ，and enhance its learning and memory ability. Its mechanism of action may be related to activation of PI 3K/Akt signaling pathway and inhibition of calpain.

Objective:To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock.Methods:An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group, and the observation parameters among the groups were compared.Results:① A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE Ⅱ score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve ( Y = -1.062 6 X2+4.407 9 X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock.② There was no significant difference in infection site, initial APACHE Ⅱ score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤1 hour group were significantly higher than those in the 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant ( P < 0.01). Conclusions:Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.

Objective:To evaluate the relationship between chemokine CXC-ligand 16 (CXCL16) and natural killer T cells during renal fibrosis in mice with acute kidney injury (AKI).Methods:Twenty-four healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), AKI group, control+ rCXCL16 group (group C-rCXCL16) and AKI+ rCXCL16 group.In AKI-rCXCL16 and AKI groups, folic acid 250 mg/kg was intraperitoneally injected to induce AKI in anesthetized mice, and rCXCL16 0.1 mg/kg and the equal volume of solution were intraperitoneally injected, respectively, at 3, 6, 9 and 12 days after injection of folic acid.The equal volume of solution and rCXCL16 were intraperitoneally injected at the corresponding time points in group C and group C-rCXCL16, respectively.The orbital blood samples were taken on day 14 after injection of folic acid for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The renal tissues were obtained for measurement of the renal fibrosis size (using Sirius red staining and Masson staining), for determination of the expression of fibronectin (FN), collagen-Ⅲ (Col-Ⅲ) and α-smooth muscle actin (α-SMA) (by immunofluorescence) and expression of interleukin-4 (IL-4), mannose receptor (CD206) and arginase 1 (Arg-1) mRNA (by real-time polymerase chain reaction), and for evaluation of the ratio of CD1d Tetramer + -IL-4 + cells (by flow cytometry). Results:Compared with group C, the serum BUN and Cr concentrations were significantly increased, the renal fibrosis size was increased, the expression of IL-4, CD206, Arg-1 mRNA, FN, Col-Ⅲ and α-SMA was up-regulated, and the ratio of CD1d Tetramer + -IL-4 + cells was increased in AKI and AKI-rCXCL16 groups ( P<0.05), and no significant change was found in the parameters mentioned above in group C-rCXCL16 ( P>0.05). Compared with group AKI, the serum BUN and Cr concentrations were significantly increased, the renal fibrosis size was increased, the expression of IL-4, CD206, Arg-1 mRNA, FN, Col-Ⅲ and α-SMA was up-regulated, and the ratio of CD1d Tetramer + -IL-4 + cells was increased in group AKI-rCXCL16 ( P<0.05). Conclusion:The mechanism by which CXCL16 is involved in the process of renal fibrosis is related to the recruitment of natural killer T cells secreting IL-4 which regulates macrophage M2 polarization in mice with AKI.

Objective To evaluate the efficacy of ultrasound-guided anterior quadratus lumborum block combined with general anesthesia for laparoscopic radical resection of rectal carcinoma. Methods A total of 80 patients of both sexes, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 40-64 yr, scheduled for elective laparoscopic radical resection of rectal carcinoma, were divided into 2 groups ( n=40 each) using a random number table method: anterior quadratus lumborum block combined with general anesthesia group ( group QG) and general anesthesia group ( group G) . In group QG, anteri-or quadratus lumborum block was performed with 0. 33％ ropivacaine 25 ml and dexamethasone 5 mg under ultrasound guidance before operation, and the same procedure was performed on the other side. Combined intravenous-inhalational anesthesia was applied, propofol 3-5μg∕ml and remifentanil 3-5 ng∕ml were given by target-controlled infusion, and cisatracurium was intermittently injected in two groups. Patient-controlled intravenous analgesia with sufentanil 2μg∕kg was used for postoperative analgesia. The analgesic pump was set up to deliver a 2 ml bolus dose with a 15-min lockout interval. Bruggrmann comfort scale ( BCS) scores were recorded at 1, 6, 12, 24 and 48 h after operation ( T1-5 ) . Tramadol was used for rescue analgesic after operation. The consumption of remifentanil and sufentanil, requirement for tramadol, occurrence of adverse reactions and patients' satisfaction with postoperative analgesia were recorded. The emergence time, first ambulation time, time to first flatus∕poo and length of hospital stay were also recorded. The develop-ment of anterior quadratus lumborum block-related complications was recorded. Results Compared with group G, BCS scores were significantly increased at T4,5 , the consumption of remifentanil, requirement for tramadol and incidence of nausea and vomiting were decreased, patients' satisfaction with postoperative an-algesia was increased, and the emergence time, first ambulation time, time to first flatus∕poo and length of hospital stay were shortened in group QG (P<0. 05). Conclusion Ultrasound-guided anterior quadratus lumborum block combined with general anesthesia can reduce the consumption of opioids in the perioperative period and is helpful in improving outcomes when used for laparoscopic radical resection of rectal carcinoma.

OBJECTIVE:To study the lifespan effect of ethyl acetate extract from Polygonum multiflora(EPM)on caenorhab-ditis elegans,and to investigate its anti-aging effect. METHODS:EPM low-concentration,medium-concentration and high- concen-tration groups(25,37.5,50 mg/L,calculated by crude drug)and blank group(0 mg/L)were established to investigate the effects of EPM on the lifespan of caenorhabditis elegans. EPM group(37.5 mg/L)and blank group(0 mg/L)were established to perform re-productive test,acute heat stress test and acute oxidative stress test of caenorhabditis elegans. The effects of EPM on reproductive capacity and pressure stress of caenorhabditis elegans were investigated. RESULTS:The lifespan test,average lifespan of cae-norhabditis elegans in EPM low-concentration,medium-concentration and high-concentration groups were prolonged significantly, compared to blank group(P<0.05 or P<0.01),especially in EPM medium-concentration group. In reproductive test,the number of offspring of caenorhabditis elegans in EPM group on the second and third day were increased significantly,compared to blank group (P<0.05). In acute heat stress test and acute oxidative stress test,average survival time of caenorhabditis elegans in EPM group was prolonged significantly(P<0.05). CONCLUSIONS:37.5 mg/L EPM can retard the aging process of caenorhabditis ele-gans and doesn’t damage the reproductive capacity.