Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Purpose: Coronavirus disease 2019 (COVID-19) infection may affect serum hormones levels and male sexual function. This study aims to provide evidence for the causal relationship between COVID-19 infection, serum testosterone levels and the risk of erectile dysfunction (ED) using a two-sample Mendelian randomization (MR) approach. Materials and Methods: Summary-level data for serum testosterone levels (199,569 samples and 12,321,875 single nucleotide polymorphisms [SNPs]) were obtained from Rebecca’s study, while data for ED (6,175 cases and 217,630 controls) were sourced from Bovijn’s study. Genetic variations linked to COVID-19 were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 6,406 cases and 902,088 controls from the COVID-19 Host Genetics Initiative.The inverse-variance weighted (IVW) method was primarily employed to evaluate the potential associations between COVID-19 infection, serum testosterone levels, and the risk of ED. The weighted mode, weighted-median and simple-median method were employed to evaluate the sensitivity. Heterogeneity and pleiotropic outlier were assessed using Cochran’s Q test and MREgger regression. Results: The MR analysis demonstrated that COVID-19 infection was associated with reduced serum testosterone levels (odds ratio [OR] 0.966, 95% confidence interval [CI] 0.938–0.993, p=0.016) and an increased risk of ED (OR 1.205, 95% CI 1.063–1.367, p=0.004) when using IVW methods. Sensitivity analyses utilizing various IV sets and MR approach remained consistent. Conclusions COVID-19 infection is associated with a decrease in serum testosterone levels and an increased risk of ED. Male patients recovering from COVID-19 need to pay special attention to their sex hormone levels and sexual health.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.