In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

Purpose To investigate the relationship be-tween the level of tumor abnormal protein(TAP)and the molec-ular subtypes and clinicopathological features of breast cancer,and to analyze the value of TAP in breast cancer screening,di-agnosis and prognosis prediction.Methods The clinical data of 357 breast cancer patients were collected,and the elbow venous blood was collected to detect the TAP condensate area.Immuno-histochemical(IHC)EnVision two-step method was used to de-tect the expression of AR,ER,PR,HER2,p53 and Ki67,and FISH to detect HER2 gene.The relationship between TAP ex-pression and clinicopathological features,molecular subtypes and clinical stages of breast cancer was analyzed,and the rele-vant literature was reviewed.Results Among 357 breast cancer patients,9 cases(2.52％)were TAP negative,36 cases(10.08％)were weakly positive,312 cases(87.40％)were strongly positive,and the positive rate of TAP was 97.48％.AR was positive in 321 cases and negative in 36 cases,ER was pos-itive in 256 cases and negative in 101 cases,PR was positive in 214 cases and negative in 143 cases,HER2 was strongly posi-tive in 98 cases,weakly positive in 214 cases and negative in 45 cases,p53 was positive in 146 cases and negative in 211 cases,Ki67 index was ≥20％in 276 cases and＜20％in 81 case.A total of 155 cases of IHC HER2(2+)breast cancer were tested by FISH:140 cases were negative and 15 cases were positive.The expression level of TAP in patients of ≥50 years old expres-sionas significantly higher than that in patients of＜50 years old(P＜0.05).The expression level of TAP in patients with high Ki67 proliferation index was significantly higher than that in pa-tients with low Ki67 proliferation index(P＜0.05).There was a significant difference in TAP expression between patients with different molecular subtypes(P＜0.05).Tap expression was higher in triple-negative breast cancer patients than in non-tri-ple-negative breast cancer patients(P＜0.05),and it was high-er in Luminal B breast cancer patients than in non-Luminal B breast cancer patients(P＜0.05).There was a significant difference in TAP expression between patients with different clin-ical stages(P＜0.05),and TAP expression level was positively correlated with clinical stage in breast cancer.Conclusion TAP detection can improve the diagnostic accuracy of breast cancer,and has a certain correlation with the survival rate and prognosis of breast cancer patients.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

OBJECTIVE To investigate the factors influencing the changes in purchasing quantity in the procurement varieties of the first batch of volume-based drug centralized procurement （hereinafter referred to as centralized procurement）. METHODS Using 25 procurement varieties of the “4+7” policy as research objects， the changes in purchasing quantity of procurement varieties were analyzed before and after the implementation of the “4+7” pilot， renewal and expansion policies. The influential factors were determined from the three levels of drugs， medical institutions and regions； and the multiple linear regression model was used to analyze the influential factors for the changes in the purchasing quantity of procurement varieties. RESULTS Before and after the implementation of the “4+7” pilot， renewal and expansion policies， the purchasing quantity increased by 52.1， －0.2， 85.8 ten thousand DDDs on average， compared with base period. During pilot， renewal and expansion period， DDDc decrease in procurement varieties was positively correlated with the increase in purchasing quantity （P＜0.01）. During the pilot and renewal period， the number of absolutely alternative varieties was positively correlated with the increase in purchasing quantity （P＜0.1）. During the pilot and expansion period， the number of alternative varieties to a certain extent was negatively correlated with the increase in purchasing quantity （P＜0.05）. During the renewal period， the increment of purchasing quantity in tertiary hospitals was smaller than that of primary medical institutions （P＜0.05）. CONCLUSIONS There is a relationship between the decline of DDDc and the changes in the purchasing quantity， that is， the more the drug price dropped， the more the purchasing quantity increased. The number of alternative varieties for centralized procurement will affect the changes in their purchasing quantity， but it is not always stable. With the implementation of the policy， the volume of primary medical institutions gradually exceeds that of tertiary institutions， indicating that the consumption of centralized purchased varieties is transferred to the primary medical institutions， and centralized procurement has promoted the implementation of the hierarchical diagnosis and treatment system.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Objective    To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods    The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results    Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial  group than those in the control group. Conclusion    For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

Objective To analyze the NBS-LRR disease resistance gene family of Codonopsis pilosula(Franch.)Nannf.and explore the disease resistance mechanism,so as to solve the problem of root rot disease of C.pilosula and promote the breeding and industrial development of C.pilosula.Methods Based on the transcriptome data of C.pilosula in response to root rot pathogen,gene structure,phylogeny,gene interaction and expression pattern of C.pilosula NBS-LRR family genes were analyzed by using bioinformatics methods.Results 88 NBS-LRR family genes were successfully identified.Including N,NL,CN,CNL,TN,TNL and PN,there are 50,14,1,14,4,3 and 2 genes respectively.Their physical and chemical properties,gene structure,phylogeny,gene interaction and expression pattern were analyzed.The results showed that CNL subfamily genes of C.pilosula were amplified during evolution;CNL and TNL gene structures ar-relatively conservative;Expression pattern analysis showed that there were differences in temporal expression patterns of C.pilosula NBS-LRR family genes under F.oxysporum infection.The highly expressed genes DN64786c1g6,DN64786c1g5,DN48234c0g2,DN54844c1g2,DN59747c0g3,DN56071c1g8,DN64591c1g1,DN48464c1g1,DN59886c0g1 play an important role in regulating the disease resistance of C.pilosula.The DN54844c1g2 may interact with GLR family,and then participate in immune regulation by regulating Ca2+ influx;DN64786c1g5 may interact with cytc-1 and cytc-2,and then participate in the response of C.pilosula to root rot by participating in redox reaction;DN59747c0g3 may interact with MPK3 and play an important role in the response of C.pilosula to root rot by participating in map signal cascade,phosphorylating WRKY transcription factor and participating in hypersensitivity reaction(HR).Conclusion The identification and expression analysis of NBS-LRR family genes of C.pilosula is of great significance to explore the mechanism of root rot resistance and gene function of C.pilosula..