The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective To develop a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of five flavonoids in Ganmao'an granules(GMA).Methods Chromatographic separation was achieved on a Kromasil C18 Column(150 mm×4.6 mm,5 μm,100 ?),which was eluted with methanol(A)-0.1％formic acid(B)at the flow rate of 1.0 ml/min.The gradient condition was as follows:0-20 min,35％A,and 20-40 min,45％A.The column temperature was 25 ℃.Analytes were detected using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in the negative ion scanning.The multiple reaction monitoring mode was used for qualitative analysis.For each flavonoid,two precursor ion/product ion transitions were chosen:lutin m/z 609.1→300.1,hyperin and isoquercitrin m/z 463.0→300.1,quercetin m/z 301.0→151.0,luteolin m/z 285.0→132.9.Results Five flavonoids showed the good relationships within their own concentration ranges(correlation coefficient r>0.999 1),whose average recoveries were in the range of 100.63％-102.81％with RSDs of 0.67％-2.07％.The content results of rutin,hyperoside,isoquercetin,quercetin,and luteolin in 10 batches of GMA were 32.23-479.83,0.291-1.825,11.44-20.54,6.32-18.41,3.46-6.51 μg/g,respectively.Conclusion The results indicated that the developed method was sensitive,accurate and could provide excellent specificity for simultaneous determination of five flavonoids in GMA.

Objective:To study the effects of group B streptococcus (GBS) colonization during late pregnancy on vaginal microbiota and neonatal outcomes.Methods:From September 2020 to September 2021, pregnant women receiving prenatal care and delivered in our hospital were prospectively enrolled. They were assigned into GBS(+) group and GBS(-) group based on the results of GBS culture and/or PCR tests of vaginal secretions. The mothers were also assigned into early-onset infection(EO) group and non-early-onset infection(non-EO) group based on the presence or absence of early-onset infection of their neonates. The vaginal microbiota and neonatal outcomes were compared between these groups.Results:A total of 125 cases were enrolled, including 65(52.0%) in GBS(+) group and 60(48.0%) in GBS(-) group. 24 cases (19.2%) were in EO group and 101 cases (80.8%) in non-EO group. The incidences of premature rupture of membranes (PROM), amniotic fluid contamination, chorioamnionitis and early-onset neonatal infection in GBS(+) group were significantly higher than GBS(-) group(all P<0.05).The abundances of Streptococcus and Ureaplasma in vaginal flora of GBS(+) group were higher than GBS(-) group ( P<0.01), whereas Rhodococcus, Phyllobacterium and Bifidobacterium were lower than GBS(-) group ( P<0.05).The EO group had significantly higher abundance of enterococcus than the non-EO group ( P<0.05). Mothers with GBS colonization and neonates with early-onset infection had the highest abundance of Escherichia/Shigella ( P=0.04). Mothers with GBS colonization and neonates without early-onset infection showed the highest abundance of Gardnerella ( P=0.04). Conclusions:GBS colonization during late pregnancy increases the incidences of PROM, amniotic fluid contamination, chorioamnionitis and early-onset neonatal infection. GBS colonization causes abnormal vaginal flora in pregnant women. The increases of Ureaplasma, Streptococcus, Escherichia/Shigella and Enterococcus in vaginal microbiota maybe associated with early-onset neonatal infection.

Objective:To analyze the general chapter for lotions 0127 of the Chinese Pharmacopoeia 2020 Vol-ume Ⅳ,and discuss how to improve the general technical requirements of lotions 0127 in the Chinese Pharma-copoeia.Methods:By comparing the general chapter for lotions in domestic and international pharmacopoe-ias,the definition,classification,process,storage and corresponding inspection requirements were analyzed.Results and Conclusions:The general chapter for lotions 0127 of the Chinese Pharmacopoeia should be revised,including improvement of the definition,increasement of forms of preparations,and expansion of included varieties,so as to promote scientific regulation for drugs and exhibit a guiding role of the Chinese pharmacopoeia in drug control.

Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. C_max of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

Objective To develop an effective decision tree management model for smart triage of nervous system diseases based on artificial neural networks and Bayesian decision theory. Methods Bayesian decision theory was used as the theoretical basis, and convolutional neural network was used to complete the rapid specialist / sub-specialist machine learning. For the specialist or sub-specialist triage data, circular neural network and Bayesian algorithm were performed to complete the probability distribution and convergence of disease symptoms and diagnosis. Results The decision tree management model and theoretical demonstration were established. According to the characteristics of the transfer learning, the rapid learning of nervous system diseases and accurate triage system, and the remote smart triage system were successfully constructed. Conclusions The management model could provide theoretical references for further use, and alleviate to some extent the currently high rate of outpatient appointment withdrawal and changes.

Objective To investigate the correlation between the number of dissected lymph nodes ( LNs) and the prognosis of patients with node?negative Siewert type ⅡAEG. Methods 248 patients with Siewert type Ⅱ AEG treated in our hospital between January 1998 and December 2008 were retrospectively assessed. All cases underwent left transthoracic subtotal esophagogastrectomy with conventional two?field lymphadenectomy, and were histopathologically proved to be without lymph node involvement. The prognostic impact of the number of dissected LNs was analyzed. Results The overall median survival time and the 1?, 3?, and 5?year overall survival rates were 64 months, 80. 4%, 60. 8% and 51. 0%, respectively. Cox regression showed that the number of dissected LNs and the depth of tumor invasion were independent prognostic factors. Patients with a high number of negative LNs had better overall survival than patients with a low number of negative LNs ( P<0.05) . The patients had better long?term survival outcomes with more than 10 LN dissected for cases with pT1 tumor ( P<0.001) , and so did those with more than 15 LN dissected for cases with pT2?3 tumor (P=0.003, 0.018, respectively). Conclusion The number of negative lymph nodes and the depth of tumor invasion are independent prognostic factors for node?negative Siewert type ⅡAEG, and adequate lymph node dissection can improve the long?term survival.

Objective To investigate the correlation between the number of dissected lymph nodes ( LNs) and the prognosis of patients with node?negative Siewert type ⅡAEG. Methods 248 patients with Siewert type Ⅱ AEG treated in our hospital between January 1998 and December 2008 were retrospectively assessed. All cases underwent left transthoracic subtotal esophagogastrectomy with conventional two?field lymphadenectomy, and were histopathologically proved to be without lymph node involvement. The prognostic impact of the number of dissected LNs was analyzed. Results The overall median survival time and the 1?, 3?, and 5?year overall survival rates were 64 months, 80. 4%, 60. 8% and 51. 0%, respectively. Cox regression showed that the number of dissected LNs and the depth of tumor invasion were independent prognostic factors. Patients with a high number of negative LNs had better overall survival than patients with a low number of negative LNs ( P<0.05) . The patients had better long?term survival outcomes with more than 10 LN dissected for cases with pT1 tumor ( P<0.001) , and so did those with more than 15 LN dissected for cases with pT2?3 tumor (P=0.003, 0.018, respectively). Conclusion The number of negative lymph nodes and the depth of tumor invasion are independent prognostic factors for node?negative Siewert type ⅡAEG, and adequate lymph node dissection can improve the long?term survival.