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.

Objective: To investigate an outbreak of acute gastroenteritis at a vocational and technical school in Shaanxi Province in 2024, ao as to provide the reference for the handling of school outbreaks. Methods: The conducted case searches, individual case investigations, and on-site hygienic investigations were established in accordance with the Guidelines on outbreak investigation, prevention and control of Norovirus infection (2015). The potential risk factors were analyzed by case-control study. Anal swab samples from cases and all canteen staff, as well as environmental swab samples were collected to detect common intestinal pathogens. All reserved food samples in canteen were collected to test for common pathogenic bacteria. Results: From October 26 to November 5, 2024, a cumulative total of 53 cases were reported, with an attack rate of 1.47%. The main clinical symptoms included vomiting (83.02%), abdominal pain (56.60%), diarrhea (30.19%), and fever (26.42%). The epidemic curve suggested an intermittent common-source outbreak, with no obvious clustering characteristics in terms of the population and spatial distribution of cases. The case-control analysis revealed that having dinner at the rice-with-dishes-on-top stall on the first floor of the canteen on October 28 was a risk factor for illness (OR=11.025, 95%CI: 2.186-55.601). GⅡ norovirus was detected as positive in anal swab samples from 6 cases and 2 asymptomatic infected canteen staff, as well as in 3 environmental swab samples from the rice-with-dishes-on-top stall. The test results for common pathogenic bacteria in the reserved food samples were all negative. Conclusions This outbreak was caused by an acute gastroenteritis epidemic induced by GⅡ norovirus infection, with a transmission pattern consistent with an intermittent homologous outbreak. The possible source of infection was asymptomatic infected canteen staff mainly through foodborne trasmission, and having meals at the rice-with-dishes-on-top stall was the primary risk factor for this outbreak.

This study aims to elucidate the role and mechanism of clematichinenoside AR(CAR) in protecting bone marrow mesenchymal stem cells(BMSCs) from hypoxia-induced apoptosis. BMSCs were isolated by the bone fragment method and identified by flow cytometry. Cells were cultured under normal conditions(37℃, 5% CO_2) and hypoxic conditions(37℃, 90% N_2, 5% CO_2) and treated with CAR. The BMSCs were classified into eight groups: control(normal conditions), CAR(normal conditions + CAR), hypoxia 24 h, hypoxia 24 h + CAR, hypoxia 48 h, hypoxia 48 h + CAR, hypoxia 72 h, and hypoxia 72 h + CAR. The cell counting kit-8(CCK-8) assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) were employed to measure cell proliferation and apoptosis, respectively. The number of mitochondria and mitochondrial membrane potential were measured by MitoTracker®Red CM-H2XRo staining and JC-1 staining, respectively. The level of reactive oxygen species(ROS) was measured with the DCFH-DA fluorescence probe. The protein levels of B-cell lymphoma-2 associated X protein(BAX), caspase-3, and optic atrophy 1(OPA1) were determined by Western blot. The results demonstrated that CAR significantly increased cell proliferation. Compared with the control group, the hypoxia groups showed increased apoptosis rates, reduced mitochondria, elevated ROS levels, decreased mitochondrial membrane potential, upregulated expression of BAX and caspase-3, and downregulated expression of OPA1. In comparison to the corresponding hypoxia groups, CAR intervention significantly decreased the apoptosis rate, increased mitochondria, reduced ROS levels, elevated mitochondrial membrane potential, downregulated the expression of BAX and caspase-3, and upregulated the expression of OPA1. Therefore, it can be concluded that CAR may exert an anti-apoptotic effect on BMSCs under hypoxic conditions by regulating OPA1 to maintain mitochondrial homeostasis.
Mesenchymal Stem Cells/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Hypoxia/drug effects* ; Homeostasis/drug effects* ; Reactive Oxygen Species/metabolism* ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects* ; Saponins/pharmacology* ; Caspase 3/genetics* ; Male ; bcl-2-Associated X Protein/genetics* ; Bone Marrow Cells/metabolism* ; Cell Proliferation/drug effects* ; Protective Agents/pharmacology* ; Cells, Cultured

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVE: Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery. METHODS: Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis. RESULTS: SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach. CONCLUSION Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Colon/pathology* ; Mucins/metabolism* ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; Male ; Colitis/metabolism* ; Cell Lineage/drug effects* ; Dextran Sulfate ; Stem Cells/drug effects* ; Disease Models, Animal

OBJECTIVE: This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes. METHODS: This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3-8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively. RESULTS: Three distinct BMI trajectory groups were identified: low-stable ( n = 1,625), medium-increasing ( n = 613), and high-increasing ( n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant ( P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes ( P < 0.001). CONCLUSION We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Humans ; Insulin Resistance ; Body Mass Index ; Male ; Female ; Middle Aged ; China/epidemiology* ; Adult ; Longitudinal Studies ; Incidence ; Diabetes Mellitus/epidemiology* ; Aged ; Obesity/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; East Asian People

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.