Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective: To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. Methods: A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. Results: After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible. Conclusion Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

Objective To understand the current practice status of central venous access device(CVAD)maintenance among intensive care unit(ICU)nurses in secondary and above medical institutions in Shandong province,and to provide a basis for further implementation of effective measures to reduce the incidence of central catheter-related bloodstream infections.Methods The CVAD maintenance practice questionnaire was compiled based on domestic and international evidence related to CVAD maintenance,and a survey was conducted in October 2022 to investigate the status of ICU nurses' CVAD maintenance practice in secondary and above medical institutions in Shandong Province.Results There were 1 492 nurses participated in the survey and 1 461 valid questionnaires were recovered,with a valid recovery rate of 97.92％.The type of CVAD used by the nurses was mainly central venous catheters[92.3％(1349/1461)],and the item with the best assessment at each operation was patency of the catheter[81.1％(1185/1461)],and the worst was the patient's feeling[40.7％(594/1 461)].When assessing catheter patency,[59.8％(873/1 461)]of nurses drew back blood into the catheter.In the use of infusion connectors,three-way connectors[76.0％(1 110/1 461)]and heparin caps[62.3％(910/1 461)]were most frequently used.When sterilizing needleless connectors,most nurses could follow the correct range of disinfection,but the time of disinfection needed to be extended,and the most used items for disinfection were povidone-iodine cotton balls/swabs[44.3％(647/1 461)].The timing of changing infusion connectors needs to be standardized.Most nurses would choose saline for catheter flushing,and the number of nurses choosing saline versus heparinized saline when locking the catheter was about 50％.Most nurses can use correct size syringes and follow standardized techniques for flushing and locking.When performing CVAD maintenance,84.7％(1 237/1 461)of nurses chose a specialized care package kit.The most used skin antiseptic was povidone-iodine[63.7％(931/1 461)].Most nurses could follow the standardized range of skin disinfection,but awareness of drying needs to be improved.Dressings covering puncture points were most frequently transparent[99.7％(1 457/1 461)]and gauze[94.7％(1 383/1 461)],and the frequency of gauze dressing changes needs to be standardized.Hand hygiene and aseptic awareness of nurses during CVAD maintenance was good,but hand hygiene and the timing of wearing sterile gloves need to be standardized.Conclusions ICU nurses' CVAD maintenance practices were generally in line with the latest evidence-based recommendations,but assessment,use of maintenance-related items,and hand hygiene and aseptic technique need to be further standardized.It is recommended that nursing administrators enhance ICU nursing human resource allocation as much as possible and form a central line associated bloodstream infection(CLABSI)prevention and control management system to gradually reduce the morbidity of CLABSI within the ICU.

Objective To understand the current situation of practice and cognition of ICU nurses on intra-abdominal pressure monitoring in tertiary general hospitals in Shandong Province,and to analyze the factors affecting their cognition,so as to provide references for formulating intra-abdominal pressure monitoring standards and procedures,and carrying out targeted training in the future.Methods A convenience sampling method was used,and a self-designed questionnaire on practice and cognition of intra-abdominal pressure monitoring was used to survey ICU nurses from tertiary general hospitals in 16 prefecture-level cities in Shandong Province from September to November 2022.Results A total of 627 valid questionnaires were collected,involving 31 tertiary general hospitals(24 tertiary A hospitals,77.42%;7 tertiary B hospitals,22.58%).The operation rate of intra-abdominal pressure monitoring was low(73.37%),and the main reasons were that they had not received intra-abdominal pressure monitoring related training(61.08%),with only 111(24.94%)nurses choosing the intersection of the mid-axillary line and the iliac crest as the reference zero point measurement,274(61.57%)nurses not taking an reading at the end of expiration.The intra-abdominal pressure monitoring cognition score was 0～16(7.88±2.79)points,and only 5 questions had a correct answer rate of≥50%.Conclusion The standardization of intra-abdominal pressure monitoring practice by ICU nurses in tertiary general hospitals in Shandong Province needs to be strengthened,and their cognition needs further training.It is suggested to unify and implement the standards and procedures of intra-abdominal pressure monitoring,further accelerate the training of intra-abdominal pressure monitoring technology,and improve the standard execution rate and cognitive level of ICU nurses on intra-abdominal pressure monitoring.

AIM:To detect the expression of basic fibroblast growth factor (bFGF) and matrix metalloprotei-nase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathological features and prognosis of the patients.METHODS:The expression of bFGF and MMP9 was detected by the method of SP immunohistochemical staining in biopsy tissues of NPC patients.The relationship between the expression and the clinical significance was analyzed as well.RESULTS:In 289 cases of NPC patients, the positive rates of bFGF and MMP9 were 71.3% and 61.6%, respectively.Correlation analysis demonstrated that the expression rates of bFGF and MMP9 were both positively associated with N stage and clinical stage in NPC patients.The high expression rates of both bFGF and MMP9 were associated with poor overall survival and progression-free survival of NPC patients.Furthermore, the positive rate of bFGF was positively correlated with that of MMP9, and over-expression of both bFGF and MMP9 was correlated with the poorest survival outcomes in NPC patients.CONCLUSION:bFGF and MMP9 are over-expressed in NPC tissues and significantly associated with NPC recurrence and poor outcome.The combined interpretation of bFGF and MMP9 expression levels leads to refinement of the risks for the NPC patients and could be chosen as the prognostic biomarkers.

Objective To investigate the clinical significance of neutrophil parameters Neut‐X and Neut‐Y in the diagnosis of blood stream infection(BSI) .Methods The data in106 patients with blood stream infection and 51 cases in the healthy control group were retrospectively analyzed .The results of WBC ,neutrophil percentage ,Neut‐X ,Neut‐Y and procaclitonin (PCT ) were compared .Results Neut‐X and Neut‐Y in the BSI group were 1 393 .5 ± 33 .4 and 416 .2 ± 30 .0 respectively ,which were signifi‐cantly higher than 1 371 .9 ± 32 .7 and 391 .7 ± 23 .7 in bacterial culture negative group and 1 347 .2 ± 26 .2 and 371 .9 ± 21 .5 in the healthy control group ,the differences were statistically significant (P<0 .05) .Neut‐X and Neut‐Y had good correlation with PCT . Neut‐X and Neut‐Y levels in the Gram‐negative bacterial group were higher than those in the Gram‐positive bacterial group .Conclu‐sion Neut‐X and Neut‐Y parameters in the patients with BSI are significantly increased and can be used as the assistant diagnosis parameters of blood stream infection .

Objective To investigate the associations of a single-nucleotide polymorphisms (SNPs) in the interleukin (IL)-6 gene with the migraine of a Han Chinese northeastern population.Methods We collected 252 patients of the migraine attack,who were diagnosed at People' s Hospital of Liaoning Province from March 2012 to June 2013,all being Han nationality in the northeast of China.At the same time,we collected 270 healthy people over the same period who had health examination or were healthy workers of People' s Hospital of Liaoning Province.We used polymerase chain reaction and gene sequencing to analyze the genotype and allele frequencies of the-572G/C (rs1800796) IL-6 polymorphisms between migraine cases (n =252;including migraine without aura (MO) group (n =168) and migraine with aura group (n =84);the male group (n =109) and the female group (n =143)) and control group (n =270;the male group (n =116) and the female group (n =152)),as well as analyzed the genotype and allele frequencies distribution between the subgroups.Results We found higher frequencies of the distribution of the C/C genotype and the C allele of the-572G/C polymorphism in migraine cases than in control group (32.54％ (82/252) vs 19.63％ (53/270),x2 =12.061,P =0.002;55.56％ (280/504) vs 45.37％ (245/540),x2 =10.818,P =0.001),higher distribution frequencies of the C/C genotype and the C allele in female group (21.83％ (55/252) vs 12.59％ (34/270),x2 =10.187,P =0.006;33.73％ (170/504) vs 26.48％ (143/540),x2 =10.073,P =0.002).Between MO group and controls,these distribution frequencies had statistically significant difference (24.60％ (62/252) vs 19.63％ (53/270),x2 =18.172,P=0.000;39.88％ (201/504) vs 45.37％ (245/540),x2 =17.307,P=0.000).After correction by conditional Logistic regression,the frequency distribution difference of the C/C genotype between the migraine cases and controls remained statistically significant (OR =22.861,95％ CI 5.218-27.098,P =0.023).Conclusion Our data indicate that the SNPs of the IL-6 are associated with migaine and the C/C genotype increases the migraine susceptibility in a Han Chinese northeastern population.

Objective To investigate which methods can promote the serum microRNA extract production.Methods The sera of healthy persons were treated with 10％ SDS (sodium dodecyl sulfate) and/or sonication at first,then extracted miRNA by routine Trizol method,or the serum miRNA was just extracted by routine Trizol method.The contents of serum miRNA-218 and miRNA-346 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique,and qRT-PCR relative quantities among different groups were compared to evaluate influence of different methods on microRNA extract efficacy.Results Compared to routine Trizol extraction method,the qRT-PCR relative quantities of miRNA-218 and miRNA-346 were improved when serum was treated with 10％ SDS and/or sonication at first (P ＜0.05),which was most obviously improved when treated with 10％ SDS combined with sonieation.Conclusions The method that serum was treated with SDS incubation and sonication at first can promote sensitivity of serum microRNA detection.

OBJECTIVETo study the effect of platelet-derived growth factor-BB (PDGFBBB) on rat corpus cavernosum smooth muscle (CCSM) cell proliferation, migration and phenotypic modulation and explore the underlying mechanisms.

METHODSWistar rat CCSM cells were obtained through a modified tissue culture method and identified by immunofluorescence assay. The effect of PDGFBB on the proliferation of CCSM cells was investigated using a CCK-8 kit and the optimum PDGFBB concentration for cell treatment was determined. CCSM cells were treated with vehicle or PDGF-BB at the optimum concentration, and the cell migration was examined using scratch assay; the mRNA expression of the transcription factor myocardin and the contractile phenotype markers αSMA and SMMHC in CCSM cells were determined by qRT-PCR at 24 h and 48 h. The protein expression of myocardin in CCSM cells incubated with PDGFBB for 0, 24 and 48 h was examined by Western blotting.

RESULTIn CCSM cell culture, 96.5%and 96% of the cells were positive for αSMA and smoothelin, respectively. PDGFBB at different concentrations markedly promoted the proliferation of CCSM cells; the optimum PDGFBB concentration for enhancing cell proliferation was 12.5 ng/mL, which induced the migration of CCSM cells and significantly reduced the mRNA expressions of myocardin, αSMA and SMMHC (P<0.01). Exposure to PDGFBB decreased the protein expression of myocardin as the exposure time extended (within 48 h).

CONCLUSIONCCSM cells of a high purity can be obtained by the modified tissue culture method. PDGFBB can promote the proliferation and migration of CCSM cells and cause a phenotypic conversion from the contractile to the synthetic type possibly by down-regulating myocardin.

Actins ; metabolism ; Animals ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Down-Regulation ; Male ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Myosin Heavy Chains ; metabolism ; Nuclear Proteins ; metabolism ; Penis ; cytology ; Phenotype ; Proto-Oncogene Proteins c-sis ; pharmacology ; RNA, Messenger ; Rats ; Rats, Wistar ; Trans-Activators ; metabolism