BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

Objective: To investigate whether zerumbone ( ZER) has the effect of preventing cisplatin ( Cis) -induced acute kidney injury (Cis-AKI) . Methods: The MTT method was used to detect the effect of different concentrations of ZER on the cell viability of Cis-AKI. The in vivo and in vitro models of Cis-AKI mice were estab- lished by dividing into control group , separate administration group , model group , and dose group. Western blot and immunofluorescence experiments were used to detect the expression changes of kidney injury marker-1 ( KIM- 1) , phosphorylated NF-κB p65 ( P-p65 ) , Cleaved casepase3 , receptor interacting protein kinase 1 ( RIPK1) , RIPK3 , and tumor necrosis factor-α (TNF-α) . Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of KIM-1 , TNF-α , interleukin-6 ( IL-6) , and monocyte chemoattractant protein-1(MCP-1) . Periodic acid-Schiff (PAS) staining confirmed the therapeutic effect of ZER on Cis-AKI. RNA-seq and cell thermal shift (CETSA) were used to explore possible target proteins. Results : MTT results showed that ZER could alleviate the decrease in cell viability of Cis-AKI ; in vivo and in vitro studies showed that compared with the model group , after treatment with ZER , its KIM-1 , P-p65 , Cleaved casepased3 , RIPK1 , RIPK3 , TNF -α expres- sion decreased significantly , and the mRNA expression of KIM-1 , TNF-α , IL-6 mRNA , and MCP-1 decreased. PAS staining showed that ZER had a therapeutic effect on Cis-AKI. RNA-seq and CETSA analysis showed that ZER might prevent and treat Cis-AKI by targeting the PIM1 protein. Conclusion ZER may alleviate Cis-AKI and im- prove inflammatory response and necroptosis by regulating PIM1 protein. ZER is expected to be a potential drug for the prevention and treatment of Cis-AKI.

Objective To observe the clinical efficacy and safety of external application of Piyan Formula in treating epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)-related rashes.Methods Sixty cases of EGFR-TKIs-related rash patients were randomly allocated into either a treatment group or a control group.The treatment group received external application of Piyan Formula to the rash area twice daily for 14 days.The control group received external application of fucidic acid cream to the rash area twice daily for 14 days.Changes in rash grading,itching grading,quality of life scores and adverse event were observed and recorded in both groups.At the same time,levels of hypersensitive C-reactive protein,interleukin(IL)-6,and IL-1β were measured before treatment and 24 hours after treatment.Results After treatment,the rash severity,itching severity,and quality of life scores were notably lower in the treatment group compared to the control group(P<0.05).The levels of hypersensitive C-reactive protein,IL-6,and IL-1β exhibited a significant decrease compared to their pre-treatment values.(P<0.05).Compared with the control group,the levels of hypersensitive C-reactive protein,IL-6,and IL-1β decreased in the treatment group,with statistically significant differences(P<0.05).No adverse events related to Piyan Formula or fucidic acid cream occurred during the treatment process.Conclusion External application of Piyan Formula in treating EGFR-TKIs-related rashes shows significant clinical efficacy,can effectively reduce the levels of inflammatory factors,and has high safety,thus warranting clinical promotion.

Objective To explore the prognostic impact of Qili Qiangxin capsules(QLQX)in patients with ST-segment elevation myocardial infarction(STEMI).Methods Retrospective collecting the clinical data of STEMI patients treated at PingAn Hospital affiliated to Hebei Medical University from January 2020 to January 2022,divided into QLQX group and non-QLQX group according to treatment plan.Follow-up patients for 1 year,with the main endpoint being major adverse cardiovascular and cerebrovascular events(MACCEs)at 30 d and 1 year;The secondary endpoints were cardiogenic death,myocardial reinfarction,emergency coronary revascularization,stroke,and major bleeding at 30 d and 1 year,as well as severe STEMI complications(30 d),re-admission due to heart failure(1 year),and all-cause mortality(1 year).Results A total of 210 STEMI patients were included(125 in the QLQX group and 85 in the non QLQX group).Univariate or Kaplan Meier analysis showed that the MACCE,cardiogenic death,malignant arrhythmia at 30 d,myocardial reinfarction,re-admission due to heart failure,and all-cause mortality rates in the QLQX group were significantly lower than those in the non QLQX group at 30 d and 1 year(P＜0.05),while there were no significant differences in the incidence of other observed endpoint events between the two groups(P＞0.05).In addition,QLQX may be a protective factor for MACCEs in STEMI patients(30 d:HR=0.157,95％CI 0.032 to 0.756,P=0.021;1 year:HR=0.208,95％CI 0.087 to 0.497,P=0.014).Conclusion QLQX adjuvant therapy may improve MACCEs in STEMI patients.

Objective:To explore the effects of self-made Huoxue Xiaozhong Xunxi Decoction combined with functional exercise on postoperative swelling of affected limbs, bone metabolism and recovery of knee function in patients with traumatic fracture of tibial plateau (FTP).Methods:Randomized controlled trial. totally 80 patients after FTP surgery in the Qidong Hospital of Traditional Chinese Medicine were enrolled and divided into two groups by random number table method from January 2018 to January 2022, with 40 cases in each group. After surgery, control group was treated with functional exercise, while observation group was additionally treated with self-made Huoxue Xiaozhong Xunxi Decoction. All were treated continuously for 8 weeks. The perioperative indexes (operation time, incision length, intraoperative blood loss, postoperative drainage volume, leaving bed time) in the two groups were recorded. The postoperative swelling and pain of affected limbs were observed, and detumescence time, pain relief time, fracture healing time and complete weight-bearing time were recorded. The knee function was evaluated by Hospital for Special Surgery (HSS). The level of serum bone morphogenetic protein-2 (BMP-2) was detected by ELISA, and total n-terminal propeptide of typeⅠprecollagen (t-PINP) and β-crossLaps (β-CTX) were detected by full-automatic immunoluminescence analyzer. The occurrence of postoperative complications in the two groups was recorded.Results:There was no significant difference in operation time, incision length, intraoperative blood loss, postoperative drainage volume or leaving bed time between the two groups ( P>0.05). The total effective rate of the observation group was 97.5% (39/40), while the control group was 80.0% (32/40), with statistical significance ( χ2=6.14, P=0.013). The detumescence time, pain relief time, fracture healing time and complete weight-bearing time were earlier in the observation group than control group ( P<0.01). After 10 d of treatment, VAS score and swelling degree in observation group were lower than those in the control group ( t=7.05, 3.81, P<0.01). After 8 weeks of treatment, levels of serum BMP-2 [(625.16±67.43) μg/L vs. (542.35±53.27) μg/L, t=6.10], t-PINP [(54.16±7.29) μg/L vs. (50.34±6.12) μg/L, t=2.54] and β-CTX [(1.26±0.38) μg/L vs. (1.04±0.23) μg/L, t=3.13] in observation group were higher than those in the control group ( P<0.05). During treatment, the incidence of complications in the observation group was 2.5% (1/40) and the control group was 7.5% (3/40), without statistical significance ( χ2=1.05, P=0.305). Conclusion:Self-made Huoxue Xiaozhong Xunxi Decoction combined with functional exercise is beneficial to improve pain and swelling of affected limbs and bone metabolism, and promote the recovery of knee function in patients after FTP surgery.

ObjectiveTo investigate the impacts of circadian misalignment on glucose uptake of skeletal muscle and metabolism in rats. MethodsA total of 36 male Wistar rats were divided into circadian alignment (CA, normal light-dark cycles, n = 18) and circadian misalignment (CM, shifted light-dark cycles, n = 18) groups. ClockLab behavior analysis was performed for 18 days (61 to 78 days after modeling). Intraperitoneal injection glucose tolerance test and physiologic measures were performed 85 days after modeling. They were euthanized 91 to 92 days after modeling, at 8:00, 12:00, 16:00, 20:00, 24:00 and 4:00 next day. Gastrocnemius tissue was collected and measured for Bmal1, Clock, Per2, Tbc1d1, Glut4 and Pgc1α by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). ResultsThe circadian cycle increased (t = -6.557, P < 0.001), the amplitude decreased (t = 2.326, P = 0.030) and the area under curve (AUC) of the blood glucose of intraperitoneal glucose tolerance test decreased (t = -2.622, P = 0.016) in CM group. In gastrocnemius, there was difference in the expression of the Bmal1 (F = 6.691, P < 0.001), Clock (F = 4.188, P = 0.007), Per2 (F = 10.893, P < 0.001), Tbc1d1 (F = 3.411, P = 0.018), Glut4 (F = 5.439, P = 0.002) and Pgc1α (F = 15.376, P < 0.001) across different time; meanwhile, there was difference in the expression of Bmal1 (F = 5.020, P = 0.035), Per2 (F = 8.996, P = 0.006), Tbc1d1 (F = 51.111, P < 0.001) and Pgc1α (F = 10.177, P = 0.004) between groups, and the total Tbc1d1 expression decreased in CM group (t = 4.349, P < 0.001). ConclusionCM induced by shifted light-dark cycles may lead to glucose tolerance impairment in rats, which may be related to the decreased expression of Tbc1d1 and the changes of transcription rhythm of Bmal1, Per2 and Pgc1α in gastrocnemius.

OBJECTIVE：To develop a metho d for determining the plasma concentration of sulfasalazine （SSZ）metabolite sulfapyridine（SP）in rats ，and to investigate the effects of esomeprazole （ESOM）on the pharmacokinetic behavior of SSZ in rats. METHODS：Male SD rats were randomly divided into SSZ group and SSZ+ESOM group ，with 6 rats in each group. SSZ+ESOM group were given Esomeprazole enteric-coated tablets [ 90 mg/（kg·d）] intragastrically for 14 days. On the 15th day ，the rats in 2 groups were given Sulfasalazine enteric coated tablets （90 mg/kg）intragastrically，and blood sample was collected from the inner canthus at 0.5，1，1.5，2，3，4，6，8，10，12，24，36，48，72 h after administration. After protein precipitation with methanol ， using diazepam as internal standard ，Agilent XDR-C 18 column was adopted with methanol- 0.1％ formic acid solution （gradient elution）as mobile phase. The concentration of SSZ metabolite SP in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by using DAS 3.0.1 software and compared between 2 groups. RESULTS ：The linear range of SP were 2-1 000 ng/mL. The methodology met the requirements of Chinese Pharmacopeia . There was no statistical significance in pharmacokinetic parameters of SP between 2 groups，such as AUC 0－t，tmax，t1/2z，cmax，MRT0－t（P＞0.05）. CONCLUSIONS ：The established method is simple ，rapid and sensitive ；it can be used for the concentration determination of SSZ metabolite SP in plasma. ESOM has no significant effect on the pharmacokinetic behavior of SSZ in rats.

Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Alkaloids/chemistry* ; Catalysis ; Enzymes/metabolism* ; Research/trends* ; Tetrahydroisoquinolines/chemistry*

Objective: To monitor the antimicrobial resistance and drug-resistance genes of Yersinia enterocolitis, Y. intermedia and Y. frederiksenii recovered from retailed fresh poultry of 4 provinces of China. Methods: The susceptibility of 25 isolated Yersinia spp. to 14 classes and 25 kinds of antibiotics was determined by broth microdilution method according to CLSI (Clinical and Laboratory Standards Institute). The antibiotic resistance genes were predicted with antibiotic resistance genes database (ARDB) using whole genome sequences of Yersinia spp. Results: In all 22 Y. enterocolitis tested, 63.7% (14 isolates), 22.8% (5 isolates), 4.6% and 4.6% of 1 isolates exhibited the resistance to cefoxitin, ampicillin-sulbactam, nitrofurantoin and trimethoprim-sulfamethoxazole, respectively. All the 25 isolates were multi-drug resistant to more than 3 antibiotics, while 64.0% of isolates were resistant to more than 4 antibiotics. A few Y. enterocolitis isolates of this study were intermediate to ceftriaxone and ciprofloxacin. Most Yersinia spp. isolates contained antibiotic resistance genes mdtG, ksgA, bacA, blaA, rosAB and acrB, and 5 isolates recovered from fresh chicken also contained dfrA1, catB2 and ant3ia. Conclusion The multi-drug resistant Yersinia spp. isolated from retailed fresh poultry is very serious in the 4 provinces of China, and their contained many kinds of drug-resistance genes.

Objective This study was to understand the structure characteristics of prophages in the genome of Enterococcus hirae R17,and also to analyze their interaction relationships with the host bacterium.Methods The gene distribution and gene encoding characteristics of prophages in the genome of Enterococcus hirae R17 were identified using the PHAST software.The virulence gene,antimicrobial resistance genes,and environmental resistance genes in the prophages were also analyzed.Results Three prophages were found on the chromosome of Enterococcus hirae,including two incomplete prophage elements (Prophage-1 and Prophage-2) and one complete prophage (Prophage-3).Some function genes of bacteria were found in the sequence of three prophages,including nucleotide transportation and metabolism related genes.One incomplete prophage carrying erythromycin-and bacitracin-resistance genes was identified in the plasmid,which suggested that prophage induced gene horizontal transfer caused erythromycin-and bacitracin-resistance of Enterococcus hirae R17.Conclusion This study laid a solid foundation for the diversity analysis of prophages of Enterococcus hirae.Prophages played an important role in promotion of antimicrobial resistance of enterococci.Scientists should pay more attention to the spread of antimicrobial resistance and pathogenicity induced by prophages.