Engineered Extracellular Vesicles in Wound Healing: Design, Paradigms, and Clinical Application.

The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.

Possible Mechanism and Treatment Results of Combined Pediatric Fractures of the Humeral Lateral Condyle and Ipsilateral Ulnar Olecranon.

OBJECTIVE: Combined fractures of the lateral condyle of the humerus and the ipsilateral ulnar olecranon are rarely seen in children. Therefore, the mechanism and suitable treatments remain debatable. This study describes the possible mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures and presents the treatment results. METHODS: Children diagnosed with combined fractures of the humeral lateral condyle and ipsilateralulnar olecranon from July 2010 to July 2020 were retrospectively analyzed. Humeral lateral condyle fractures were treated with open reduction and internal fixation with bioabsorbable pins. Ulnar olecranon fractures were treated with closed reduction and percutaneous pinning with K-wires for Mayo type IA fractures and with tension-band wiring or a locking plate for Mayo type IIA fractures. The postoperative function and appearance of the elbow were evaluated using the Flynn criteria and Mayo Elbow Performance Score (MEPS) at follow-up. RESULTS: The cohort comprised 19 patients aged from 4 to 11 years. Bony compression and avulsion by attached muscles and ligaments may be the leading factors causing the combined injuries, as the children fell with an outstretched and supinated elbow. The average follow-up time was 33 months. High MEPS of >90 indicated that good to excellent results were obtained without complications. CONCLUSIONS: This study proposed a reasonable hypothesis for the mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures in children. Satisfactory outcomes were achieved with bioabsorbable pins for lateral condyle fractures and closed reduction and percutaneous pinning with K-wires, tension-band wiring, or locking plate for olecranon fractures.

A Rare Combined Injury in Children during Side Impact: The Possible Mechanism and Treatment Results.

OBJECTIVE: Proximal humeral fracture combined with contralateral midshaft clavicle fracture is an extremely rare injury in children. Few studies focus on the injury mechanism and treatment scheme. The aim of this study is to propose the possible mechanism of this injury and present the treatment results. METHODS: This retrospective study included children diagnosed with proximal humeral fractures combined with contralateral midshaft clavicle fractures from August 2016 to March 2019 in the corresponding author's institution. The patients received elastic stable intramedullary nails and external fixation as treatment. The radiological and clinical outcomes of treatments were evaluated using the imaging and the Constant-Murley score (CMS) in follow up. RESULTS: Twelve patients (eight males and four females) with an average age of 7.83 years old (age 5-12) were included in this research. All the patients had suffered a side impact in a road traffic accident or outdoor environment. Hypothesis about the mechanism was the proximal humerus was directly impacted at first and caused the surgical neck fracture, then the contralateral shoulder hits the solid object and the contralateral midshaft clavicle was fractured. During the average 45.2 months (range 36-57) follow-up, all the patient's fractures achieved clinical and radiological union before 14 weeks without complications. Every patient had a satisfactory score (range from 92 to 100) on the CMS criteria for both shoulders. CONCLUSION: The hypothesis about the mechanism of this combined injury in this study sounds reasonable. It highlights the need for safety-related education about using a safety seat or wearing a seat belt to parents and caregivers, so as to avoid such injury even if the treatment with external fixation (EF) and proximal humeral and elastic stable intramedullary nailing (ESIN) showed good results.

Immune homeostasis modulation by hydrogel-guided delivery systems: a tool for accelerated bone regeneration.

Immune homeostasis is delicately mediated by the dynamic balance between effector immune cells and regulatory immune cells. Local deviations from immune homeostasis in the microenvironment of bone fractures, caused by an increased ratio of effector to regulatory cues, can lead to excessive inflammatory conditions and hinder bone regeneration. Therefore, achieving effective and localized immunomodulation of bone fractures is crucial for successful bone regeneration. Recent research has focused on developing localized and specific immunomodulatory strategies using local hydrogel-based delivery systems. In this review, we aim to emphasize the significant role of immune homeostasis in bone regeneration, explore local hydrogel-based delivery systems, discuss emerging trends in immunomodulation for enhancing bone regeneration, and address the limitations of current delivery strategies along with the challenges of clinical translation.

Successful treatment of ceftazidime/avibactam combined with aztreonam in the NDM-producing Klebsiella pneumoniae bloodstream and intestinal infections in a NK/T lymphoma patient with agranulocytosis during autologous hematopoietic stem cell transplantation: a case report.

New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae is increasingly reported worldwide. Clinicians face significant challenges in the treatment of this multidrug-resistant bacterium. The combination of ceftazidime/avibactam (CAZ/AVI) and aztreonam (ATM) is currently probably the most effective strategy for the treatment of such infection. We described a patient diagnosed with NK/T cell lymphoma who underwent autologous hematopoietic stem cell transplantation (ASCT) in the hematology department. The patient developed severe infection after ASCT. Blood and stool cultures showed carbapenem-resistant K. pneumoniae. Blood sample was detected as NDM-producing K. pneumoniae. We successfully treated this infection with CAZ/AVI and ATM.

High-throughput design of high-performance lightweight high-entropy alloys.

Developing affordable and light high-temperature materials alternative to Ni-base superalloys has significantly increased the efforts in designing advanced ferritic superalloys. However, currently developed ferritic superalloys still exhibit low high-temperature strengths, which limits their usage. Here we use a CALPHAD-based high-throughput computational method to design light, strong, and low-cost high-entropy alloys for elevated-temperature applications. Through the high-throughput screening, precipitation-strengthened lightweight high-entropy alloys are discovered from thousands of initial compositions, which exhibit enhanced strengths compared to other counterparts at room and elevated temperatures. The experimental and theoretical understanding of both successful and failed cases in their strengthening mechanisms and order-disorder transitions further improves the accuracy of the thermodynamic database of the discovered alloy system. This study shows that integrating high-throughput screening, multiscale modeling, and experimental validation proves to be efficient and useful in accelerating the discovery of advanced precipitation-strengthened structural materials tuned by the high-entropy alloy concept.

[Analysis of theoretical basis and clinical application of dog-days moxibustion].

The present situation of the clinical application of dog-days moxibustion (moxibustion applied in the three periods of the hot season) is summarized so as to provide the guide for the theoretic study and clinical application of dog-days moxibustion. The intervention time of dog-days moxibustion is on the 1st day of each of the three periods of the hot season. Simultaneously, the geographic factors are considered. The disorders of lung system are mostly dominant among the indications of dog-days moxibustion, complicated with spleen and stomach disorders as well as cold and deficiency syndromes/patterns. The acupoints are mainly selected from the front-mu points on the chest and the back-shu points on the back, in combination with the differentiation of diseases, symptoms/patterns and the disorder stages. The duration of treatment is ranged from 1 to 3 years. The clinical therapeutic effect is improved constantly along with the increase of treatment periods by years.

Chinese multicentre prospective registry of breast cancer patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC): a study protocol.

INTRODUCTION: Available patient-reported outcome (PRO) studies are mainly from single institution or of small sample size, and the variations across hospitals and regions were not fully analysed. A multicentre, prospective, patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC) will be planned to assess the PROs of Chinese patients with breast cancer who will undergo breast reconstruction (BR) or oncoplastic breast-conserving surgery (OBCS). METHODS AND ANALYSIS: The inclusion criteria are female patients with breast cancer aged >18 years old who will undergo BR or OBCS. This cohort will include at least 10 000 consecutive patients (about 5000 patients who will undergo BR and 5000 patients who will undergo OBCS). The exposures were surgery types: BR and OBCS regardless of the techniques and materials used. The primary endpoint will be PROs, which include BREAST-Q and quality of life (European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and EORTC QoL Breast Cancer-specific version (QLQ-BR23)). All patients will be followed up to 24 months after operations. All data will be prospectively collected using an app software. Data will be analysed using SPSS and Stata software. ETHICS AND DISSEMINATION: This study follows the Helsinki Declaration. All patients will be asked to sign an informed consent before enrolment. The results of this study will be presented at national and international meetings and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04030845; Pre-results.

Numb confers to inhibit epithelial mesenchymal transition via ß-catenin/Lin28 signaling pathway in breast cancer.

OBJECTIVES: This study aimed to investigate role of Numb in the epithelial mesenchymal transition (EMT) of breast cancer. METHODS: Numb and ß-catenin were inhibited in MCF-7 cells using sh-RNA and overexpressed in T47D cells by pcDNA3.0-Numb, pcDNA3.0-ß-catenin. Cell proliferation, invasion and migration were evaluated using MTT and Transwell assay, respectively. ß-catenin, Lin28, and EMT related markers were determined using qRT-PCR and Western Blotting. RESULTS: Knockdown of Numb significantly promoted the proliferation, invasion and migration of MCF-7 cells, further increased the expression of ß-catenin, Lin28, Snail-1, and N-cadherin, as well as decreased E-cadherin. In T47D cells transfected with pcDNA3.0-Numb, the results were quite the reverse. CONCLUSIONS: Knockdown of Numb could promote the EMT of breast cancer cells via ß-cateni/Lin28 signaling pathway.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Multicenter cross-sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations.

Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC). Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA- patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive BC (P=0.02). The present study provides a general BRCA mutation profile in the Chinese population. The prevalence of BRCA mutation in BC patients with high hereditary risk is lower compared with Western populations. Chinese mutation type is different with Western people, without obvious founder mutation.

Finite-temperature stress calculations in atomic models using moments of position.

Continuum modeling of finite temperature mechanical behavior of atomic systems requires refined description of atomic motions. In this paper, we identify additional kinematical quantities that are relevant for a more accurate continuum description as the system is subjected to step-wise loading. The presented formalism avoids the necessity for atomic trajectory mapping with deformation, provides the definitions of the kinematic variables and their conjugates in real space, and simplifies local work conjugacy. The total work done on an atom under deformation is decomposed into the work corresponding to changing its equilibrium position and work corresponding to changing its second moment about equilibrium position. Correspondingly, we define two kinematic variables: a deformation gradient tensor and a vibration tensor, and derive their stress conjugates, termed here as static and vibration stresses, respectively. The proposed approach is validated using MD simulation in NVT ensembles for fcc aluminum subjected to uniaxial extension. The observed evolution of second moments in the MD simulation with macroscopic deformation is not directly related to the transformation of atomic trajectories through the deformation gradient using generator functions. However, it is noteworthy that deformation leads to a change in the second moment of the trajectories. Correspondingly, the vibration part of the Piola stress becomes particularly significant at high temperature and high tensile strain as the crystal approaches the softening limit. In contrast to the eigenvectors of the deformation gradient, the eigenvectors of the vibration tensor show strong spatial heterogeneity in the vicinity of softening. More importantly, the elliptic distribution of local atomic density transitions to a dumbbell shape, before significant non-affinity in equilibrium positions has occurred.

Machine learning to parse breast pathology reports in Chinese.

INTRODUCTION: Large structured databases of pathology findings are valuable in deriving new clinical insights. However, they are labor intensive to create and generally require manual annotation. There has been some work in the bioinformatics community to support automating this work via machine learning in English. Our contribution is to provide an automated approach to construct such structured databases in Chinese, and to set the stage for extraction from other languages. METHODS: We collected 2104 de-identified Chinese benign and malignant breast pathology reports from Hunan Cancer Hospital. Physicians with native Chinese proficiency reviewed the reports and annotated a variety of binary and numerical pathologic entities. After excluding 78 cases with a bilateral lesion in the same report, 1216 cases were used as a training set for the algorithm, which was then refined by 405 development cases. The Natural language processing algorithm was tested by using the remaining 405 cases to evaluate the machine learning outcome. The model was used to extract 13 binary entities and 8 numerical entities. RESULTS: When compared to physicians with native Chinese proficiency, the model showed a per-entity accuracy from 91 to 100% for all common diagnoses on the test set. The overall accuracy of binary entities was 98% and of numerical entities was 95%. In a per-report evaluation for binary entities with more than 100 training cases, 85% of all the testing reports were completely correct and 11% had an error in 1 out of 22 entities. CONCLUSION: We have demonstrated that Chinese breast pathology reports can be automatically parsed into structured data using standard machine learning approaches. The results of our study demonstrate that techniques effective in parsing English reports can be scaled to other languages.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

[Acupuncture combined with western medicine for CP/CPPS:a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy differences among acupuncture combined with western medicine, acupuncture alone and western medicine alone for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Ninety patients were randomly assigned into a needle-medicine group, an acupuncture group and a western medicine group, 30 patients in each group. The patients in the needle-medicine group were treated with acupuncture combined with western medicine; the scalp points included Shenting (GV 24), Xinhui (GV 22), Qianding (GV 21), Baihui (GV 20), Chengguang (BL 6), Tongtian (BL 7), etc. The body points were Zhongji (CV 3), Guanyuan (CV 4), Pangguangshu (BL 28), Ciliao (BL 32), etc. The acupuncture was given 30 min per treatment, once a day. Besides, oral administration of 0.2g levofloxacin (twice per day) and 0.2 mg tamsulosin (once a day) was applied. The patients in the acupuncture group and western medicine group were treated by acupuncture and western medicine respectively. 12-d treatment was taken as one session, and totally 2 sessions were given. The clinical efficacy of the three groups after treatment was compared as well as the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total score and pain score, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) before and after treatment. RESULTS: During the trial two patients dropped out, as a result, 30 patients in the needle-medicine group, 29 patients in the acupuncture group and 29 patients in the western medicine group were included in the analysis. After treatment, 21 patients were cured, 6 patients were markedly effective, 2 patients were effective and 1 patient failed in the needle-medicine group;12 patients were cured, 10 patients were markedly effective, 5 patients were effective and 2 patients failed in the acupuncture group; 11 patients were cured, 12 patients were markedly effective, 4 patients were effective and 2 patients failed in the medicine group; the efficacy in the needle-medicine group was superior to those in the acupuncture group and medicine group (both P<0.05). Each score was improved after treatment in each group (all P<0.01); the total score of NIH-CPSI as well as SAS and SDS scores in the needle-medicine group were superior to those in the acupuncture group and medicine group (P<0.05, P<0.01); the pain scores of NIH-CPSI in needle-medicine group and acupuncture group were superior to that in the medicine group (P<0.05, P<0.01), but the difference between the needle-medicine group and acupuncture group was not significant (P>0.05). CONCLUSIONS: The efficacy of acupuncture combined with western medicine for CP/CPPS is superior to that of acupuncture alone and western medicine alone, which could improve the symptom of prostatitis as well as status of anxiety and depression.

An epidemiological analysis of paediatric burns in urban and rural areas in south central China.

OBJECTIVE: This study aims to analyse the epidemiology of paediatric burns in south central China, illustrate the differences between rural and urban areas, and discern prevention measures to reduce paediatric burns. METHODS: Data were obtained from all paediatric patients admitted to Department of Burns unit of Xiangya Hospital during 2009-2012. A retrospective review was performed, including cause of burn, pre-hospital treatment, place of burn occurrence, anatomical areas involved, extent of burn, date of injury, number of operations, complications, length of hospital stay, hospitalisation cost and cure rate. RESULTS: A total of 278 hospitalised paediatric patients were admitted in this study. The majority (56.47%) were 1-3 years old. Rural patients accounted for 67.99% in total; the ratio of boys to girls was 2.05. Scalding with hot fluids was the most common cause of burns in children (62.59%), followed by flame (17.63), fireworks (9.71%), electricity (5.76%) and other factors such as contact and chemical (4.32%). The living room was the location with the highest frequency of burns in children (53.24%). Burns were more likely to happen in winter and the upper extremities were the most involved anatomic site (53.24%). Total burn surface area (TBSA) ranging from 0% to 9% accounted for 55.4% in total. Rural patients underwent more operations and had longer and costlier hospital stays than urban patients. CONCLUSION: Compared with treatment in urban areas, rural burn patients received less first-aid treatment, underwent more surgery, had more complications and longer and more costly hospital stays. This finding strongly suggests that it is necessary to make more efforts to prevent burns, especially in rural areas.

Interleukin-2 gene polymorphisms and prognosis of breast cancer.

Breast cancer is the most common malignancy in women. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect of polymorphisms in the IL-2 gene on the development of breast cancer in the Chinese population. IL-2-330T/G and +114T/G polymorphisms were assessed in 638 breast cancer cases and 682 age-matched healthy controls. Data were analyzed using the chi-square test. Results showed that individuals with -330TG genotype and -330GG genotype had significantly increased susceptibility to breast cancer (Odds ratio [OR]=1.42, 95% confidence interval [CI]: 1.10-1.79, p=0.0021 and OR=2.26, 95%CI: 1.53-3.30, p<0.0001). The +114T/G polymorphism did not show any correlation with breast cancer. In addition, when analyzing the survival time of breast cancer patients with IL-2-330T/G polymorphism, cases with a -330G allele had significantly shorter survival time compared with wild-type patients (p=0.002). These results suggested that polymorphism in the IL-2 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.

Complex nonlinear deformation of nanometer intergranular glassy films in beta-Si3N4.

The mechanical properties of a model of Y-doped intergranular glassy film in silicon nitride ceramics are studied by large-scale ab initio modeling. By linking directly to its electronic structure, it is shown that this microstructure has a complex nonlinear deformation under stress and Y doping significantly enhances the mechanical properties. The calculation of the electrostatic potential across the film supports the space charge model in ceramic microstructures.

Electronic structure and bonding in hydroxocobalamin.

The electronic structure of hydroxocobalamin (OHCbl) has been calculated by a density functional method, using the orthogonalized linear combination of the atomic orbitals method (OLCAO). The X-ray crystal structure has been determined from synchrotron X-ray diffraction data and the geometry determined was used in the calculations. Comparison with the recently reported electronic structures of cyanocobalamin (CNCbl), methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) shows that Mulliken charges (Q*) and bond orders (BO) vary only on the axial fragment.

Accurate redetermination of the X-ray structure and electronic bonding in adenosylcobalamin.

The electronic structure of adenosylcobalamin (B12 coenzyme, AdoCbl) has been calculated by a density functional method, using the orthogonalized linear combination of the atomic orbital method (OLCAO). Since a fixed accurately determined geometry was needed in such calculations, the crystal structure of adenosylcobalamin has been redone and refined to R = 0.065, using synchrotron diffraction data. Comparison with the recently reported electronic structures of cyano- (CNCbl) and methylcobalamin (MeCbl) shows that the net charges and bond orders vary only on the axial donors. The values in the three cobalamins suggest that the Co-C bond in MeCbl has a strength similar to that in AdoCbl, but it is significantly weaker that that in CNCbl. Present results are compared with those previously reported for the analogous corrin derivatives; i.e., simplified cobalamins with the side chains a-f replaced by H atoms. Despite a qualitative agreement, a discrepancy in the calculated HOMO-LUMO gap is found.