ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Objective:To explore the structural characteristics of intestinal microflora in children with non-alcoholic fatty liver disease（NAFLD）and the relationship between intestinal microflora and the occurrence as well as development of NAFLD in children.Methods:Fifteen children with NAFLD diagnosed at the First People's Hospital of Yunnan Province from January 2022 to December 2022 were selected as subjects，and 15 healthy children who received routine physical examinations at the outpatient clinic during the same period were randomly selected as healthy control group.The height，weight，waist circumference，blood pressure，blood biochemistry of all children were collected.At the same time，the fresh fecal samples of all children were collected，and the biological information of intestinal flora was analyzed by 16S rRNA sequencing.Results:In the NAFLD group，there were eight males and seven females，with an average age of（11.13±1.77）years.In healthy control group，there were seven males and eight females，with an average age of（9.73±2.25）years.There were no significant differences in sex，age，blood pressure between two groups.Compared with the healthy control group，the levels of body mass index，waist circumference，waist-to-height ratio，alanine aminotransferase，aspartate transaminase，gamma-glutamyl transpeptidase，total bilirubin，direct bilirubin，unconjugated bilirubin，low density lipoprotein cholesterol，uric acid and serum insulin significantly increased and high density lipoprotein cholesterol significantly decreased in NAFLD group（ P<0.05）.The results of species diversity analysis showed that chaol index and observed-species index in NAFLD group were significantly higher than those in healthy control group（ P<0.05）.Species diversity analysis showed that the species with increased abundance in NAFLD group included：Proteobacteria，Gammaproteobacteria，Enterobacteriaceae，Klebsiella，Escherichia-Shigella，Escherichia-Shigella-unclassified.Differential species with increased abundance in the healthy control group included：Bifidobacterium species，Bifidobacterium，Bifidobacteriaceae，Bifidobacteriales，Actinobacteria，Actinobacteriota，Bacteroidia，Bacteroidales，Streptococcus-thermophilus. Conclusion:There are metabolic abnormalities and obvious changes in the structure of intestinal flora in children with NAFLD.Exogenous supplementation of Bifidobacterium，Streptococcus thermophilus and Bacteroides may prevent the occurrence of NAFLD，delay the progression of disease and improve fat deposition in the liver.

Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.

Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe(BOC2)on the expression of six types of mitochondrial N-formyl peptides(NFPs)in blood and two formyl peptide receptors(FPRs)in pancreatic tissue of rats with severe acute pancreatitis(SAP),and to explore its mechanism of alleviating inflammatory damage of SAP.Methods Forty male SD rats were randomly divided into four groups:the sham group,the SAP model group,the BOC2 low-dose and the BOC2 high-dose group(0.1 and 0.2 mg/kg),with 10 animals in each group.The SAP model was prepared by retrograde injection of 5%sodium taurocholate(50 mg/kg)into biliary and pancreatic ducts in the last 3 groups.BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling,and samples were taken 4 hours after modeling.HE staining was used to observe pathological changes in pancreas.Western blot assay was used to detect the expression of NFPs in plasma.IHC staining was used to detect the expression of FPRs in pancreatic tissue.ELISA was used to detect interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α levels in plasma.qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue.Results Compared with the model group,the BOC2 high-dose group and the BOC2 low-dose group showed improvement in pathological phenomena,such as pancreatic bleeding,acinar cell necrosis,inflammatory cell infiltration and edema.The pancreatic injury score,pancreatic FPRs expression,plasma MT-ND1,MT-ND2,MT-ND3,MT-ND5,MT-ND6 expression,as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue,were significantly reduced(P＜0.05).Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.

Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.

ObjectiveTo explore the mechanism of Chaihu Guizhitang （CHGZT） in alleviating neuropathic abdominal pain induced by 2，4，6-trinitrobenzene sulfonic acid （TNBS） in rats with chronic pancreatitis （CP）. MethodFifty male SD rats were randomly assigned into five groups： sham operation， CP model， and low-， medium-， and high-dose （4， 8， and 16 g·kg^-1， respectively） CHGZT groups. In the sham operation group， the abdomen was closed after the pancreas was gently stirred. The rat model of CP was established by retrograde injection of 2% TNBS-10% ethanol into the pancreatic duct. The oral administration of CHGZT started 4 weeks after modeling and lasted for 2 weeks. Pain threshold was measured by Von Frey fibers 6 weeks after surgery. Hematoxylin-eosin （HE） staining was employed to reveal the chronic inflammation and fibrosis of the pancreatic tissue. Immunohistochemmistry （IHC） was employed to detect the expression of PGP9.5 （a marker of pancreatic nerves） and reveal the inflammatory changes around the nerves. IHC and immunofluorescence （IF） were used to determine the location of ionized calcium-binding adaptor molecule-1 （Iba-1， microglia marker） and purinergic receptor P2X7 （P2RX7） and the co-expression of P2RX7 and Iba-1 in the thoracic spinal dorsal horn. ResultCompared with the sham operation group， the modeling increased the scores of pancreatic gland atrophy， inflammatory infiltration， and fibrosis （P<0.01）， the abdominal pain response under different force values （P<0.05， P<0.01）， and the score of peripancreatic inflammation. Moreover， the modeling up-regulated the expression of Iba-1 and P2RX7 in the thoracic spinal dorsal horn （P<0.01）. Compared with the model group， the high- and medium-dose CHGZT lowered the scores of pancreatic gland atrophy， inflammatory infiltration， and fibrosis， the abdominal pain response， and the score of peripancreatic inflammation （P<0.05， P<0.01）. The high-， medium-， and low-dose CHGZT all down-regulated the expression of Iba-1 and P2RX7 （P<0.01）. ConclusionCHGZT can significantly relieve abdominal pain in CP rat by suppressing the inflammation around nerves in the pancreas and the P2RX7 activation of microglia in the spinal dorsal horn.

Objective:To investigate the association of tumor necrosis factor-α(TNF-α)gene G308A single nucleotide polymorphism(SNP)with childhood obesity and metabolic disorders.Methods:A total of 620 obese children admitted to our pediatric department from January 2015 to December 2019 were selected as research subjects, who were divided into metabolic non-healthy group( n=267)and metabolic healthy group( n=353), and 260 healthy children were selected as the control group. Single nucleotide polymorphism of TNF-α gene G308A was detected, serum TNF-α level, obesity indicators, glucose and lipid metabolism indicators were compared among the children in various groups. Results:No significant differences in body mass index(BMI), waist circumference, hip circumference, and serum TNF-α level were found between metabolic non-healthy group and metabolic healthy group( P>0.05), but higher than those in control group( P<0.05). There were no significant differences in fasting plasma glucose(FPG)and total cholesterol(TC) levels among the three groups( P>0.05). The levels of fasting insulin(FINS), fasting glucagon(FGC), HbA 1C, triglyceride(TG), and low density lipoprotein-cholesterol(LDL-C)in metabolic non-health group and metabolic health group were significantly higher than those in control group, higher in metabolic non-health group compared with metabolic healthy group( P<0.05). HDL-C level in two obese groups was significantly lower than that in control group, lower in metabolic non-health group compared with metabolic healthy group( P<0.05). The frequencies of GG genotype and allele G in metabolic non-healthy group and metabolic healthy group were significantly lower than those in control group, lower in metabolic non-health group compared with metabolic healthy group. The frequencies of AA, GA genotypes and allele A were significantly higher in metabolic non-health group than those in metabolic healthy group( P<0.05). There were no significant differences in TNF-α, FPG, and TC among AA, GA and GG groups( P>0.05). BMI, waist circumference, hip circumference, FINS, FGC, HbA 1C, TG, HDL-C and LDL-C were comparable between AA type and GA type( P>0.05), but revealed a significant difference compared with GG type( P<0.05). Pearson correlation analysis showed that the level of TNF-α was positively correlated with BMI, waist circumference, hip circumference, FPG, FINS, FGC, HbA 1C, TC, TG, and LDL-C( P<0.05), but negatively correlated with HDL-C( P<0.05). Conclusion:TNF-α gene G308A single nucleotide polymorphism is associated with obesity and metabolic disorders in children.

Essential palatal tremor is relatively rare in clinical practice, which manifests involuntary and rhythmic contraction of soft-palate along with auditory click. The cause is unknown and there is no specific treatment at present. This article reports a female patient with essential palatine tremor, who presented with involuntarily beating of soft palate, disappeared during sleep, had sensory tricks, and gradually developed mental and psychological problems such as anxiety disorders. After treatment with integrated traditional Chinese and Western medicine, the symptoms improved. The clinical features of the case were analyzed, relevant literature was reviewed, and the possible etiology and characteristics of the disease were explored, so as to provide reference for clinical diagnosis and treatment.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.