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.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

ObjectiveTo investigate the application of endoscopy in obtaining the great saphenous vein （GSV） during coronary artery bypass grafting （CABG） and explore the learning curve， with a particular focus on common challenges encountered during the learning process and their impact on early clinical outcomes. MethodsA retrospective analysis was conducted on clinical data from 83 patients who underwent off-pump CABG with endoscopic GSV harvesting at the First Affiliated Hospital of Zhengzhou University from July 2013 to April 2014. Patients were categorized into four groups based on the chronological order of their hospitalization： Group A （novice group， n=20）， Group B （proficient group， n=20）， Group C （progressive group， n=20）， and Group D （mature group， n=23）. Differences in perioperative and midterm follow-up outcomes among the groups were analyzed to determine the learning curve period. ResultsThe study population had a mean age of （60.22±8.06） years and a mean body weight of （69.77±11.66） kg. Comorbidities included hypertension （24 cases）， diabetes （26 cases）， and subacute cerebral infarction （14 cases）. The novice group exhibited significantly shorter GSV length-to-harvest time ratio relative to the other three groups （P<0.001） and a significantly higher incidence of main vein damage （P=0.006）. However， there was no statistically significant difference in graft patency at the 1-year follow-up. ConclusionThorough and reliable technical training in endoscopic GSV harvesting is essential to minimize vascular injury caused by novice operators. Approximately 20 cases of hands-on experience and a careful self-analysis of procedural challenges are likely required to achieve proficiency in GSV harvesting.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

BACKGROUND:Grape seed extract has been shown to be effective in inhibiting the growth of androgen-dependent tumors(e.g.,breast cancer),and thus grape seed extract could theoretically inhibit epiphyseal closure induced by estrogen in late adolescence. OBJECTIVE:To screen the effects of grape seed extract on apoptosis of growth plate chondrocytes and epiphyseal closure in rats. METHODS:(1)In vitro experiment:Growth plate chondrocytes from rat large tibia and femur at logarithmic growth stage were obtained and cultured in groups:normal control group,model control group(adding 17β-estradiol to induce apoptosis),positive control group(adding letrozole and 17β-estradiol),grape seed extract group(adding 17β-estradiol and 10 μg/mL grape seed extract),Caspase-9 inhibitor group(adding 17β-estradiol and Caspase-9 inhibitor),Caspase-9 agonist group(adding 17β-estradiol and Caspase-9 agonist).Cell apoptosis was detected by flow cytometry after 48 hours of culture.(2)In vivo experiment:Thirty 3-month-old Sprague-Dawley rats were randomly divided into model control group,positive control group and low-,medium-and high-dose groups,with five rats in each group.All rats were injected subcutaneously with 17β-estradiol(3 times per week)to establish epiphyseal closure models,followed by intragastric administration of letrozole in positive control group and 0.05,0.2 and 0.8 g/kg grape seed extract in low-,medium-and high-dose groups,respectively,once a day until over 2/3 of the epiphyseal plate in the model control group was closed.The length of the tibia was then observed.Another 18 Sprague-Dawley rats were randomly divided into model control group,positive control group,and medium-dose group,with 6 rats in each group,treated as above for 1.5 continuous months.The expression of Caspase-9 protein in rat growth plate cartilage was detected by western blot. RESULTS AND CONCLUSION:(1)In vitro experiment:17β-estradiol could induce apoptosis in growth plate chondrocytes,and letrozole,grape seed extract,and caspase-9 inhibitors could all inhibit apoptosis in growth plate chondrocytes.(2)In vivo experiment:When more than 2/3 of the epiphyseal plate in the model control group was closed,the number of rats with epiphysis closure in the positive control and medium-dose groups was less than that in the model control group(P＜0.05),and the tibial length was longer than that in the model control group(P＜0.05),and the Caspase-9 protein expression in the tibial growth plate was lower than that in the model control group(P＜0.05).To conclude,the appropriate dose of grape seed extract can effectively inhibit the apoptosis of growth plate chondrocytes and delay epiphyseal closure,which has the potential to promote bone growth.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

To further standardize the diagnosis and treatment of hypertension after kidney transplantation in China,Branch of Organ Transplantation of Chinese Medical Association organized experts in kidney transplantation and cardiovascular diseases to formulate"Guidelines for Clinical Diagnosis and Treatment of Hypertension in Kidney Transplant Recipients in China"based on"Diagnosis and Treatment Specification for Hypertension after Solid Organ Transplantation in China(2019 edition)"in combination with clinical status of hypertension after organ transplantation in China,and referring to the latest guidelines for diagnosis and treatment of hypertension at home and abroad.This guideline was formulated to provide theoretical reference for medical practitioners in the field of kidney transplantation in China,aiming to better control adult hypertension after kidney transplantation,mitigate adverse outcomes and improve the quality of life.

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.

Objective:To introduce the experience of reconstructing the pelvic floor with a pedicled large omental flap combined with a basement membrane biological mesh in combined pelvic organ resection for locally advanced or locally recurrent rectal cancer combined with sacrococcygeal resection, and to discuss the feasibility, safety, and near-term therapeutic efficacy of this technique.Methods:For patients with sacrococcygeal resection of combined pelvic organs, a basement membrane mesh was used to rebuild the pelvic floor with a pedicled greater omentum flap to isolate the abdominopelvic cavity. The main operation was to pull the greater omentum, which preserved the double vascular arches, to the pelvic floor to cover the pelvic floor, and then the mesh was used to cover the posterior peritoneal defect and pelvic inlet with absorbable sutures of 2-0 or thicker.Results:In this study, a retrospective cohort study was used to collect clinical data through the China Rectal Cancer Combined Pelvic Organs Resections Case Database. Twenty patients with locally advanced or locally recurrent rectal cancer without extra-pelvic metastasis or only oligometastases underwent combined pelvic organ and sacrococcygeal resection in the Department of Anal and Intestinal Surgery of the Second Affiliated Hospital of the Naval Military Medical University during the period of July 1, 2022, to June 30, 2023, and 10 patients underwent simple basement membrane resection with a simple basement membrane. Among them, the pelvic floor were reconstructed by basement membrane mesh alone in 10 cases (mesh only group), and 10 cases were reconstructed the pelvic floor by pedicled large omental flap combined with basement membrane mesh (omental flap-combined mesh group). The recent outcomes of the two groups of patients were studied comparatively. Comparison of baseline data and intraoperative conditions between the two groups showed no statistically significant differences (all P>0.05); the drain removal time in the omental flap-combined mesh group was 26.7 (19-42) days, which was shorter than that in the mesh only group, which was 40.4 (24-56) days ( U=4.125, P=0.001); The empty pelvis healing time in the omental flap-combined mesh group was 29.4 (23~43) days, which was shorter than that of 42.2 (27~58) days in the mesh-only group ( U=4.043, P=0.001); the differences were all statistically significant. The postoperative complication rate of grade ≥III in the omental flap-combined mesh group was 1/10, which was lower than that of 6/10 in the mesh-only group; the difference was not statistically significant when comparing the two groups ( P = 0.057). Follow-up ended on 09/30/2023, with a median follow-up of 9.5 (3-15) months in 20 patients, and all 20 cases survived during the follow-up period, with no tumor recurrence at the surgical site. Conclusion:In locally advanced or locally recurrent rectal cancer undergoing combined pelvic organ resection with sacrococcygeal, compared with reconstruction of the pelvic floor by basement membrane mesh alone, reconstruction of the pelvic floor and isolation of the abdominopelvic cavity by a pedicled greater omentum flap combined with a basement membrane mesh is safe and feasible.