Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective    To compare and investigate the efficacy and differences of modified B-T shunt, central shunt and right ventricle-pulmonary artery (RV-PA) connection in the treatment of pulmonary atresia with ventricular septal defect (PA/VSD). Methods    A total of 124 children with PA/VSD underwent initial palliative repair in Shanghai Children's Medical Center from September 2014 to August 2019, including 63 males and 61 females, aged 7 days to 15 years. They were divided into in a modified B-T shunt group (55 patients), a central shunt group (22 patients) and a RV-PA connection group (47 patients). The clinical data of these children were retrospectively analyzed. Results    There were 9 early deaths after palliation, with an early mortality rate of 7.3%. The mean follow-up time was 26.5±20.3 months, with 5 patients lost to follow-up, 5 deaths during the follow-up period, and 105 survivors. The 1-year and 5-year survival rates were both 89.7%. The monthly increased Nakata index was 5.2 (–0.2, 12.3) mm2/m2, 9.2 (0.1, 23.6) mm2/m2, 6.3 (1.8, 23.3) mm2/m2 in the modified B-T shunt group, the central shunt group, and the RV-PA connection group, respectively, with no statistical difference among the three groups. The 1-year survival rate was 85.3%, 78.4%, 95.2%, and the 5-year (4-year in the central shunt group) survival rate was 85.3%, 58.8%, 95.2% in the three groups, respectively, with a statistical difference among them (P<0.05). The complete repair rate was 36.5%, 19.0% and 67.4% in the three groups, respectively, with a statistical difference among the three groups (P<0.001). Conclusion    All these three palliative surgical approaches can effectively promote pulmonary vascular development. But compared with systemic-pulmonary shunt, RV-PA connection has a lower perioperative mortality rate and can achieve a higher complete repair rate at a later stage, which is beneficial for long-term prognosis.

Background Some studies have shown that PM_2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM_2.5-induced depression- and anxiety-like behaviors in mice. Objective To observe the effects of PM_2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM_2.5. Methods Eight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM_2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM_2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM_2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. Results The percentage of open-arm entry [M(P₂₅, P₇₅)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (\begin{document}$\bar x \pm s $\end{document}) in the PM group were (2.01±0.90) m and (10.31±1.99) s respectively, shorter than those of the NS group [(3.80±0.89) m, (14.47±3.07) s], the total travelled distance in the PML group [(2.73±1.12) m] was shorter than those of the NS group and the LGG group [(4.21±1.08) m], and the differences were statistically significant (P<0.05). Compared to the NS group, the Simpson index of the PM group significantly increased (P<0.05). Compared to the LGG group, the Simpson index of the PML group significantly decreased (P<0.05). The results of Beta diversity analysis showed that there were differences in the composition of intestinal flora among the four groups of mice. Compared with the NS group and the LGG group, the abundances of Erysipelotrichaceae and Dubosiella in the PM group and the PML group increased, while the abundances of Prevotellaceae_UCG-001 decreased, and the differences were statistically significant (P<0.05). In hippocampus, the level of 5-HT in the PM group [(135.02±10.31) μg·g⁻¹] was lower than those in the NS group [(178.77±43.15) μg·g⁻¹] and the LGG group [(224.85±22.98) μg·g⁻¹], and the level of 5-HT in the PML group [(161.27±15.81) μg·g⁻¹] was lower than that in the LGG group (P<0.05). 5-HT level in hippocampus was significantly positively correlated with the relative abundance of Prevotellaceae_UCG-001 (r=0.6090, P=0.012). The percentage of open-arm entry was significantly negatively correlated with the relative abundance of Dubosiella (r=−0.4630, P=0.023). Conclusion Atmospheric PM_2.5 exposure may cause depression- and anxiety-like behaviors in mice. The observed behavior dysfunction may be associated with the changes in diversity and relative abundance of intestinal flora as well as the decrease of 5-HT level. Such depression- and anxiety-like behaviors are alleviated after adding probiotics.

Objective To analyze how enterovirus D68 (EV-D68) protease 2A affects the anti-vi-ral interferon typeⅠ(IFN-Ⅰ) pathway in 293T cells following infection. Methods Western blot was used to detect the expression of recombinant protease 2A, IFN-α and signal transducers and activators of tran-scription 1 (STAT1) at protein level. Expression of EV-D68 viral protein (VP1) and protease 2A was ana-lyzed by immunofluorescence at different time points. Cytopathic effects were recorded to calculate 50％ cell culture infective dose ( CCID50 ) . Expression of the genes involved in the anti-viral IFN-Ⅰ pathway was measured by real-time PCR (RT-PCR). Results The recombinant plasmid pCLIPf-2A was successfully constructed and the expression of recombinant protease 2A could be detected by Western blot 24 h after transfection. The recombinant protease 2A promoted the proliferation of EV-D68 at the late stage of infection and induced the production of IFN-α. Expression of the genes involved in the anti-viral IFN-Ⅰ pathway at mRNA level was up- or down-regulated to different degrees with various trends in different groups following infection. Expression of STAT1 was enhanced in all groups. Conclusions EV-D68 protease 2A promoted the activation of anti-viral IFN-Ⅰpathway in response to viral infection and enhanced the proliferation of virus at the late stage of infection.

Objective To explore the relationship between the polymorphisms of the primary gout predisposing gene (BCAS3) rs11653176 locus and the incidence of gout in Han Chinese men in coastal areas of Shandong Province. Methods One hundred and fifty-two cases of patients with gout remission,68 cases of acute stage,252 patients with hyperuricemia, and 280 healthy subjects, total males, were enrolled. Genotyping the rs11653176 locus of BCAS3 gene by TaqMan probe technique. The expression level of BCAS3 gene mRNA in each PBMC was measured by RT-qPCR. The levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-18(IL-18)in serum were measured by ELISA. Results The change of allele frequency of rs11653176 locus in BCAS3 gene was associated with gout(P<0.01). BCAS3 mRNA in patients with gout was significantly higher than that of healthy people and patients with hyperuricemia(P<0.01). In gout patients, the expression level of BCAS3 gene containing C allele was higher than that of T allele(mRNA,P<0.05). The inflammatory factors in the acute phase of gout were significantly higher than those in phases of remission and hyperuricemia(P<0. 01). Conclusion Changes in the allele frequency of BCAS3 alleles rs11653176(high C, low T)may contribute to the expression of this gene,and lead to gout. And the onset of gout is closely related to the production of inflammatory factors.

Objective To investigate the characteristics of VP1 gene hypervariable region in hu-man enterovirus type 68(HEV68)strains isolated in China. Methods Nucleotide sequences of the VP1 gene in the Chinese strains and strains isolated in other countries were aligned by using Clustal W in the MEGA6 program. The phylogenetic trees were constructed by using Neighbor-Joining(NJ)method in the MEGA6 program. Sequence of the amino acids encoded by that region was analyzed by compared with that of the standard strain Fermon. Results A total of 80 strains of EV68 had been isolated in China by the end of 2015. Most of the mutations occurred in BC and DE loops. The mutation sites lied in the VP1 gene of Chi-nese isolates were at 83,89,91,94,96,97,98,102,109,139,141,142,143,144 and 147. Glycine was missing from most of the amino acid sequences encoded by the VP1 gene of Chinese strains. The phylo-genetic analysis indicated that 53 and 21 EV68 strains isolated in China belonged to B and C clades,respec-tively. Conclusion Compared with the standard strain Fermon,the Chinese strains changed a lot in BC-loop and DE-loop,which were associated with the antigenicity and virulence of EV68. The EV68 strains iso-lated in China belonged to B and C clades.

Objective:To evaluate the value of transesophageal echocardiography(TEE)in postoperative low cardiac output syndrome of critical cardiac valvular disease.Methods:The preoperative data of 16 patients with critical cardiac valvular disease who suffered from postoperative low cardiac output syndrome,as well as the postoperative treatment of them,was retrospec-tively analyzed.Results:Among the 16 patients,9 cases underwent intra-aortic balloon pump(IABP)support suggested by TEE.And 7 of the 9 patients recovered without complications,while the other 2 patients died.IABP were not suggested by TEE in 7 patients,2 of whom underwent exploratory thoractomy,while the other 5 patients recovered after adjustment of vas-opressor agents and improvement of internal environment.Conclusions:TEE can be used in the differentiation of the cause of postoperative low cardiac output syndrome in patients with critical cardiac valvular disease and it can provides the basis for the reasonable application of IABP.

Objective To determine the influence of gender on the association between serum uric acid and branchial-ankle pulse wave velocity (baPWV).Methods Cross-sectional data from 1418 adults who underwent routine laboratory tests and baPWV measurements were analyzed in a gender-specific manner.BaPWV≥ 1400 cm/s was defined as abnormality.The individuals were assigned to four groups (Q1,Q2,Q3 and Q4) according to the gender-specific quartiles of serum uric acid.The relationship between serum uric acid and the baPWV values was assessed by Spearman's correlation coefficients.In female,the relationship of serum uric acid quartiles with baPWV was evaluated by logistic regression analysis.Results In male and female,diastolic blood pressure,fasting blood glucose,triglyceride and body mass index were increased with serum uric acid level,in contrast to high-density lipoprotein cholesterol.The Spearman's correlation coefficient for the relationship between serum uric acid and baPWV was 0.18 in female and-0.05 in male (P =0.16).In female,univariate logistic regression analysis showed that in comparison with group Q1,odds ratio (OR) value of baPWV abnormality of group Q4 was 2.45 (95％confidence interval (CI) 1.48 to 4.06).In multivariate logistic regression,after adjusting for creatine and estimated glomerular filtration rate,OR value of baPWV abnormality of group Q4 was 2.45 (95％ CI 1.48 to 4.06) when compared with group Q1.However,after adjustment for age and other risk factors of cardiovascular diseases,there were no significant differents in ORs among serum uric acid quartile groups.Conclusions The association between serum uric acid level and baPWV in female may depend on age and metabolic syndrome components.