Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

The incidence and mortality of hepatocellular carcinoma (HCC) in China are among the highest in the world, imposing a heavy social burden. Liver resection and liver transplantation are the primary radical treatments for HCC, although most patients are no longer able to meet the surgical requirements at initial diagnosis. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) has the advantages of shrinking tumors, enlarging residual liver, regressing portal vein tumor thrombus and improving the quality of life, which can be used for conversion, downstaging and bridging therapy for HCC before surgical treatment, enabling patients regain the chance of radical treatment and reducing the postoperative recurrence rate. This review focuses on the clinical application and progress of ⁹⁰Y-SIRT in this field.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Objective To analyze the metabolomics characteristics of chronic atrophic gastritis(CAG)patients with liver-stomach qi stagnation and spleen-stomach weakness syndromes based on non-targeted metabolomics technology,and to identify the serum differentiated metabolites related to traditional Chinese medicine(TCM)syndrome of CAG patients,so as to provide a reference for the objectification of syndrome differentiation.Methods Sixty patients with CAG were included,including 30 cases of liver-stomach qi stagnation syndrome and 30 cases of spleen-stomach weakness syndrome.Fasting blood of 5 mL was collected from the cubital vein of patients in the two groups,and the serum levels of metabolites were detected by ultra-high-performance liquid chromatography-mass spectrometry(UPLC-MS)methods.The principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and cluster analysis were used to screen the differentiated metabolites of CAG patients with liver-stomach qi stagnation syndrome and spleen-stomach weakness syndrome.Finally,metabolite pathway analysis was performed for the obtained differentiated metabolites using the KEGG database.Results The results for the screening of differentiated metabolites showed that significant differences of amino acid derivatives and small peptide metabolites were presented between CAG patients with liver-stomach qi stagnation syndrome and CAG patients with spleen-stomach weakness syndrome.The amino acid derivatives consisted of N-acetylglycine,histamine,O-phosphoserine,selenomethylselenocysteine,and methyl-tyrosine.And the small peptide metabolites consisted of tyrosine-leucine-phenylalanine,histidine-alanine-glutamate-lysine,L-asparagine-L-proline-L-serine,and L-isoleucine-L-isoleucine.Conclusion Differences in amino acid metabolism exist between CAG patients with liver-stomach qi stagnation syndrome and those with spleen-stomach weakness syndrome,and metabolites such as N-acetylglycine,intermethyltyrosine,and O-phosphoserine may be the potential biomarkers for distinguishing liver-stomach qi stagnation syndrome from spleen-stomach weakness syndrome in CAG patients.

Objective:To investigate the expression of platelet receptor CD62P in septic rats and the anti-inflammatory effect of ticagrelor and its protective effect on myocardial injury in septic rats.Methods:Thirty-two male SD rats were randomly(random number) divided into 4 groups: sham group, cecal ligation and puncture group(CLP), low dose group: the dose of 10 mg/kg, high dose group: the dose was 50 mg/kg, 8 rats in each group. The rats in the sham operation group were only treated with abdominal switch and cecum stripping, and the rats in the sepsis group, the low dose group and the high dose group were treated with CLP method to establish the sepsis model. The rats in the ticagrelor administration group were treated with ticagrelor at a dose of 10 mg/kg and 50mg/kg by gavage, respectively. The sham operation group and the sepsis group were treated with normal saline (1 mL/kg) by gavage. The rats were administrated twice by gavage 12 hours before and 12 hours after surgery. Blood samples were collected from the abdominal aorta 24 hours after modeling and then pathological specimens were collected. The expression of platelet surface receptor CD62P was detected by flow cytometry. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The levels of myocardial injury markers including CKMB and LDH were detected. The levels of transaminase, creatinine and white blood cell were detected. HE staining was used to observe the pathological morphology of myocardial tissue. Cardiomyocyte apoptosis was observed by TUNEL assay.Results:① Compared with sham group, the expression of CD62P in CLP group significantly increased ( P<0.01). Compared with the CLP group, the expression levels of CD62P in the two treatment groups significantly decreased, and the HD group was more significant ( P <0.01).②ELISA results showed that compared with sham group, the level of IL-6 in CLP group was significantly increased ( P<0.05). Compared with the CLP group, the HD group significantly decreased ( P< 0.05). There was no significant decrease in IL-6 level in the LD group. The level of TNF-α in CLP group was significantly higher than that in sham group ( P< 0.01). ③ Compared with sham group, the expression levels of CKMB and LDH in CLP group and two ticagrelor intervention groups significantly increased ( P <0.01). Compared with the CLP group, CKMB and LDH in the treatment group significantly decreased ( P <0.05), and the HD group decreased more significantly ( P<0.01). ④ Compared with sham group, WBC, ALT, CR values in CLP group significantly increased, while after the intervention with ticagrelor, WBC, ALT, CR values in rats significantly decreased ( P <0.05), and the difference significantly related to the dose. ⑤ The pathological results showed that the morphology of myocardial cells in sham group was normal. The CLP group most myocardial cell injury. LD and HD group the CLP group obviously reduce myocardial cell injury.⑥ Tunel staining showed that compared with a small number of positive cells in Sham group, a large number of positive cells were stained in CLP group. The apoptosis of myocardial cells in LD and HD groups significantly reduced compared with CLP group. Conclusions:Sepsis activates platelets and stimulates the overexpression of CD62P, which induces excessive activation of inflammatory response, induces apoptosis and damage of cardiomyocytes, and leads to septic myocardial injury. The cardioprotective effect of ticagrelor may be related to the inhibition of the reduction of CD62p expression after platelet activation, and the expression level of CD62p has a dose-dependent relationship with ticagrelor.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.

Objective:To explore the methods and clinical effects of reconstructing facial and cervical scars with expanded flaps based on the "MLT" principle.Methods:The study was a retrospective observational study. From January 2019 to May 2022, 74 patients with facial and cervical scars after burn or trauma injuries who met the inclusion criteria were admitted to Xiangya Hospital of Central South University, including 38 males and 36 females, aged from 5 to 58 years, including 24 patients with simple facial involvement, 24 patients with simple cervical involvement, and 26 patients with both facial and cervical involvement, with scar area ranging from 12 to 145 cm2. By following the "MLT" principle (color and texture similar to the face; flap area large enough to reconstruct the entire defect; skin tissue thin enough to transmit the expression, so as to facilitate the shape of the face and five features); in the stage Ⅰ surgery, the skin and soft tissue expanders (hereinafter referred to as the expanders) were implanted, and in the stage Ⅱ surgery, the expander removal+scar resection+flap transplantation to repair the secondary wound was performed, and the wound in the donor area of flap was directly sutured. After operation, silicone gel preparation and laser therapy were used to prevent scar hyperplasia. The expansion ratio and time period of expanders, the occurrence of complications of skin and soft tissue expansion surgery, the type of flap used, and the survival of flap after the stage Ⅱ surgery were observed and recorded. The long-term effect of facial and cervical reconstruction and the recovery of donor area and recipient area of flap were evaluated during the postoperative follow-up after surgery.Results:The expansion ratio of 135 expanders ranged from 1.36 to 3.00 times, and the expansion time period ranged from 6 to 14 months. During skin and soft tissue expansion surgery, 8 patients had poor healing of incisions after expander placement, 7 patients had expander rupture, 5 patients had infection in incisions after expander placement, 3 patients had expander exposure, 2 patients had difficult filling the injection pot, and 1 patient had water leakage from the injection pot. Dorsal shoulder expanded flaps with double blood supply of transverse cervical artery and circumflex scapular artery were used in 8 patients, the expanded flaps of anterior transverse carotid artery perforator were used in 11 patients, the expanded flaps of internal thoracic artery perforator were used in 12 patients, tandem expanded flaps of upper chest and neck were used in 16 patients, dorsal thoracic artery perforator expanded flaps were used in 5 patients, and adjacent rotary propulsive expanded flaps were used in 22 patients. After the stage Ⅱ surgery, the flaps of 71 patients were completely survived. One patient had blood circulation disorder in the flap, and the flap survived after hyperbaric oxygen treatment. Necrosis occurred at the end of the flaps in 2 patients, which healed after dressing change. After the surgery, 42 patients were followed up for 3 to 24 months. The color, texture, and thickness of flaps were good and similar to the surrounding normal skin tissue in the recipient area, the appearance and function of the face and neck were significantly improved, and the wound location in the donor and recipient areas of flaps was concealed with slight scar formation.Conclusions:In the reconstruction of facial and neck scars, by following the "MLT" principle, the expanded flap was carefully designed before surgery, the local aesthetic features within the subunit are reconstructed during the stage Ⅱ surgery, and standard anti-scar treatment measures are actively adopted after surgery. After reconstruction, the color, texture, and thickness of flaps were close to the normal skin in face and neck, and the appearance and function of face and neck are significantly improved, with less linear scars left. It is beneficial to improve the therapeutic effect.