Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.
Male ; Humans ; Middle Aged ; Enteral Nutrition ; Intestines/surgery* ; Intestinal Diseases ; Abdomen/surgery* ; Anastomosis, Surgical ; Abdominal Injuries/surgery*

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*