The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Methods: Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1, 2020, to October 30, 2021 were enrolled as the research participants in the study. They were assigned to two groups based on traditional Chinese medicine (TCM) syndrome types: heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group. Healthy volunteers who underwent health check-ups in the Health Management Department were included as healthy group following the random number table method. The tears of the patients and the healthy volunteer participants were tested by high-performance liquid chromatography-mass spectrometry (LC-MS). The differential metabolites were screened out by multivariate statistical analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed on the differential metabolites. Finally, the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites. Results: A total of 32 dry eye patients were enrolled, including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern. Fourteen healthy volunteers were included as healthy group. There were no significant differences in baseline characteristics among the three groups (P > 0.05). A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group, mainly including lipids, lipid-like molecules, organic acids and their derivatives, organic heterocyclic compounds, and nucleosides and their analogues. For heat stagnation in liver meridian pattern group, 112 metabolites were determined, mainly including organic acids and their derivatives, lipids, and lipid-like molecules. The KEGG enrichment results of pathways and the relative content analysis of differential markers demonstrate that purine metabolism and caffeine metabolism pathways are common metabolic characteristics of all dry eyes. Among them, deoxyinosine monophosphate (dIMP) and 2-(formamido)-N1-(5-phospha-D-ribosyl) acetamidine can serve as their biomarkers. The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation, ovarian steroidogenesis, cholesterol metabolism, pyrimidine metabolism, and bile secretion (P < 0.05). Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine, leucine, and isoleucine biosynthesis pathways (P < 0.05). Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification. Different patterns of dry eye syndrome exhibit typical characteristics in the types and concentrations of metabolites, which correspond to the syndrome classification in TCM. This study initially confirms the rationality of TCM syndrome classification and provides significant reference for the mechanism of dry eye and drug development.

Natriuretic peptides(NPs)are closely associated with acute ischemic stroke(AIS),and previous studies have shown that NPs have the beneficial effects of promoting vasodilation and inhibiting inflammation and apoptosis.The beneficial cardiovascular effects of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with the natriuretic peptide receptor A/cyclic guanosine monophosphate(cGMP)signaling pathway.With the discovery of C-type natriuretic peptide(CNP)and its dependent receptor natriuretic peptide receptor B in brain tissue,NPs provide new ideas for the diagnosis and treatment of AIS.Recent studies have confirmed the beneficial effects of ANP,BNP,CNP,and their homologous receptors on neuronal damage induced by AIS;however,the specific mechanism of pathways mediated by NPs remains unknown.This article summarizes the studies on NPs,cGMP,and AIS,in order to provide a ref-erence for subsequent studies on NPs in AIS.

Objective This article aimed to explore the inhibitory effect of β-ionone(BI)on the proliferation of breast canc-er cells through the nuclear factor kappa-B(NF-κB)pathway and its possible mechanism.Methods The methylene blue assay and MTT assay were used to determine the viability of breast cancer cells.The malachite green phosphate assay was used to detect the ac-tivity of protein phosphatase 2A(PP2A).Western blot was used to detect the levels of phosphorylated P65(s534 and s311)(p-P65),PP2A(A,B and C),and phosphorylated ataxia telangiectasia mutant(p-ATM)(s1981)protein.Results BI could significant-ly inhibit the proliferation of human breast cancer BT549 cells and MCF-7 cells in a time-and dose-dependent manner,and the difference was statistically significant(P<0.01).After treated with BI,NF-κB activity was significantly inhibited in MCF-7 cells,as shown by a significant decrease in the level of phosphorylated P65(s311 and s534)protein and an increase in the level of PP2A pro-tein,and the difference was statistically significant(P<0.05).In addition,BI also significantly reduced the phosphorylation of P65 protein and ATM protein in MCF-7 cells by the PP2A inhibitor-okada acid(OA).Conclusion This study shows that BI inhibits the proliferation of breast cancer cells by inhibiting NF-κB activity,and its mechanism may be achieved by increasing PP2A activity to regulate the NF-κB pathway.

γ-Tocotrienol(γ-T3)is a common phytochemical belonging to a major subclass of natural vitamin E,mainly de-rived from palm oil and rice bran.Compared to saturated tocopherol(TOC),the γ-T3 side chain contains unsaturated bonds and forms isoprene chains.γ-T3 has therapeutic activity for various chronic diseases with broad potential applications,especially in inhib-iting tumor proliferation and invasion.With deeply research,more and more evidence suggests that γ-T3 plays an important role in inhibiting cancer cell migration and metastasis,inducing tumor cell apoptosis,arresting cell cycle and regulating cancer-related sig-naling pathways.Therefore,this article will review the anti-cancer effects and mechanisms of γ-T3.

In recent years,the overall incidence of cancer and mortality have been on an upward trend,cancer becomes a public health problem that seriously endangers human health in the world. Currently,except for radiotherapy and surgery to cancer treatment,chemotherapy plays an important role in greatly improving the survival rate of cancer patients. However,most of chemothera-pies have drug-resistance and toxic effects on patients. In order to overcome these shortcomings,some natural phytochemicals have been used as chemosensitizers in chemotherapies. These natural phytochemicals not only increase the sensitivity of tumor cells to ther-apeutic drugs,but it also reduces their resistance and toxic effects on patients. Therefore,this review summarizes the sensitization of natural phytochemicals to target drug therapies and their possible mechanisms.

Objective To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study. Methods From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients′ parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results Totally 1 100 cases met inclusion criteria, with median age 36 years (range 20-44 years), median follow-up 35 months (range 1-108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383) and 29.6%(82/277) patients achieved amenorrhea respectively (P<0.01). Total and subclassification of adverse effects decreased significantly (P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status (all P>0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.

Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with menorrhea in a prospective study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including scores of menstruation blood loss, carrying status of IUS, symptoms and scores of dysmenorrhea, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Changes of pictorial chart scores of menstruation and distribution of anemia during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 618 cases (56.18%, 618/1 100) had severe menorrhea, with median follow-up period of 28 months (range 1-60 months), and accumulative carrying rate of 66% at 60 months follow-up. After placement of LNG-IUS, compared with baselines, pictorial chart scores and ratio of menorrhea had decreased significantly (all P<0.01), the scroes of menstruation were 157±34, 94±35, 70±33,67 ± 18, 67 ± 20, 65 ± 19, 66 ± 19, 65 ± 21 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 24 months after placement of LNG-IUS, pictorial chart scores and distribution of anemia had improved significantly compared with preceding period (all P<0.01). We found no dependent factors predicting improvement of pictorial chart scores of menorrhea, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). Conclusions LNG-IUS is effective for adenomyosis of menorrhea. Improvement of menstruation blood loss is independent on patients characters, menstruation patterns or adverse effects.

Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1 ± 0.9, 5.5 ± 2.4, 4.6 ± 2.4, 3.3 ± 2.2, 2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). Conclusion LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.

Objective To study effects of different degree of hypothyroidism in severe preeclampsia (S-PE) pregnant women on renal function and the correlation between them.Methods 46 S-PE patients with subclinical hypothyroidism (SCH) registered for treatment in the Shengjing Hospital of China Medical University from May 2011 to March 2013 were selected into SCH group,and 23 S-PE with overt hypothyroidism (OH) were selected into OH group,and 109 S-PE with normal thyroid stimulating hormone (TSH) levels were selected into simple group.Thyroid hormone and kidney function tests were analyzed in pregnant women with S-PE.We made an analysis of the relative risk of the detection rate of abnormal renal function and also the relationship between the levels of thyroid hormone and serum uric acid,serum urea and creatinine in patients with S-PE.Results (1) In SCH group serum TSH was (6.1±3.2) mU/L,free triiodothyronine (FT3) was (4.0±0.6) pmol/L,free thyroxine (FT4) was (11.8± 1.5) pmol/L; in OH group serum TSH was (5.2± 1.3) mU/L,FT3 was (3.7±0.6) pmol/L,FT4 was (9.3±0.5) pmol/L; in simple S-PE group serum TSH was (1.9±0.8) mU/L,FT3 was (4.0±0.8) pmol/L and FT4 was (11.9±1.9) pmol/L.TSH in SCH group was significantly higher than that in simple S-PE group (P＞0.01),the difference of in SCH and OH group were not statistically significant (P＞0.05).The difference of FT3 in three groups were not statistically significant (P＜0.05) ;FT4 in OH group was significantly lower than thoes in SCH and simple groups (P＜0.05).(2)Serum uric acid,creatinine and urea levels in OH group was (436± 114),(75± 15) μmol/L and (6±3)mmol/L,in simple S-PE group they were (378± 114),(65 ±22) μmol/L and (5±3) mmol/L.In comparison,the differences was statistically significant(P＜0.05).The differences were not statistically significant in SCH and OH groups (P＞0.05).(3)The abnormal detection rate of uric acid was significantly higher in SCH than that in OH group [46％ (21/46) versus 22％ (5/23),OR=3.0,P＜0.05].The comparison of remaining index has no statistical significance(P＞0.05).(4)In SCH group there was a significant inverse correlation of serum FT3 with serum urea levels,serum creatinine and serum uric acid (r=-0.32,-0.58,-0.35,P＜0.05).There was not a correlation of serum TSH,FT4 with indicators of renal function (P＞0.05).In OH group there was a negative correlation between FT3 and serum creatinine concentrations (r=-0.40,P＜0.05).In OH group there was not a correlation of FT3 with serum uric acid and urea (P＞0.05).There was a positive correlation between TSH and serum creatinine in simple S-PE group (r=0.20,P=0.04).There was not a correlation between TSH and serum urea(r=0.04,P=0.65),and serum uric acid (r=0.12,P=0.20).Conclusions There was effect of different hypothyrosis state in pre-eclampsia patients on renal function.Serum uric acid,urea and creatinine concentrations in S-PE pregnant women with OH were significantly higher than those in simple S-PE group with normal TSH.There was a negative correlation between FT3 and serum creatinine in S-PE.Hence the thyroid function should be regularly monitored in S-PE patients to find damage of renal function and management hypothyrosis.