PURPOSE: Different arch structures may cause different foot function injuries. In the past, the arch structure and flexibility of the foot were often defined by the height of the arch, and there was no three-dimensional (3D) structure classification method. In order to form a more complete 3D description, we propose a new classification system of arch volume flexibility (AVF), and then use this new classification system to investigate the relationship between the AVF and arch index (AI), and the arch height flexibility (AHF) and AI, respectively. METHODS: It is proposed to recruit 180 young male adults for the test. We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement. Based on these data, we calculated the AHF and the AVF. Using the quintile method, these arches are divided into very stiff, stiff, neutral, flexible, and very flexible. According to AI value, all arches were divided into cavus, rectus, and planus. The distribution of AVF was compared using χ² goodness of fit test. The spearman correlation test was used to compare the AHF and AVF. A p < 0.05 indicates that the difference is statistically significant. RESULTS: All participants' plantar data was obtained through 3D scanning, but only 159 of them were complete, so only 318 feet had valid data. The left AHF is (21.23 ± 12.91) mm/kN, and the right AHF is (21.71 ± 12.69) mm/kN. The AVF of the left foot arch is (207.35 ± 118.28) mm³/kg, while the right one is (203.00 ± 117.92) mm³/kg, and the total AVF of the arch was (205.17 ± 117.94) mm³/kg. There was no statistical difference in the AVF between the left and right feet for the same participant (n = 159, p = 0.654). In cavus, the percentage of arch with AVF is 21.4% (very stiff), 21.4% (stiff), 14.3% (neutral), 7.1% (flexible), and 35.7% (very flexible). In rectus, the percentage of arch with AVF is 23.9% (very stiff), 19.6% (stiff), 14.7% (neutral), 24.5% (flexible), and 17.2% (very flexible). In planus, the percentage of arch with AVF is 14.9% (very stiff), 20.6% (stiff), 27.0% (neutral), 16.3% (flexible), and 21.3% (very flexible). Moreover, the correlation between AHF and AVF is not significant (p = 0.060). CONCLUSION In cavus, rectus, and planus, different AVF accounts different percentage, but the difference is not statistically significant. AVF is evenly distributed in the arches of the feet at different heights. We further found the relationship between AHF and AVF is not significant. As a 3D index, AVF may be able to describe the flexibility of the arch more comprehensively than AHF.
Adult ; Humans ; Male ; Foot ; Foot Injuries ; Biomechanical Phenomena

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active ulcerative colitis (UC).Methods:From November 1, 2020 to October 30, 2022, at the Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, 81 UC patients who received VDZ treatment and completed a 14-week follow-up were retrospectively selected. The clinical data of patients, including age, disease duration, disease activity of UC were collected. The VDZ efficacy evaluation included primary and secondary efficacy indicators. The primary efficacy indicator was the clinical remission rate after 14 weeks of VDZ treatment, and the secondary efficacy indicators included the clinical response rate, steroids-free remission rate, endoscopic remission rate after 14 weeks of treatment as well as the clinical response rate, clinical remission rate, steroids-free remission rate, secondary loss of response rate after 52 weeks of treatment. The adverse reactions during the treatment were recored. Taking clinical remission after 14 weeks of treatment as the dependent variable, univariate analysis was performed to identify the risk factors affecting clinical remission of VDZ. Binary logistic regression analysis was used for multivariate analysis to determine the independent risk factors of VDZ-included clinical remission. Chi-square test and Wilcoxon signed-rank test were used for statistical analysis.Results:Among the 81 UC patients, the age was 40.0 years old (29.0 years old, 53.5 years old) and the disease duration was 42.5 months (22.5 months, 94.7 months). The proportion of patients with mild active UC was 21.0% (17/81), the proportion of patients with moderate active UC was 64.2% (52/81), and the proportion of patients with severe active UC was 14.8% (12/81). After 14 weeks of treatment, the total Mayo score decreased from baseline level of 7.0 (6.0, 9.0) to 1.0 (0.0, 3.0), and the difference was statistically significant ( Z=-6.87, P<0.001). The clinical response rate was 84.0% (68/81) and the clinical remission rate was 69.1% (56/81) after 14 weeks of treatment. Of the 17 patients treated with combination of corticosteroid therapy, 10 achieved steroid-free remission, and the endoscopic remission rate was 34.8% (23/66). Of the 43 patients followed up to 52 weeks, the total Mayo score of UC patients decreased from baseline level of 7.0 (6.0, 9.0) to 0.0 (0.0, 1.0) after 52 weeks of treatment, and the difference was statistically significant ( Z=-3.25, P<0.001). The clinical response rate was 69.8% (30/43), and the clinical remission rate was 65.1% (28/43). Of the 13 patients treated with combination of corticosteroid therapy, 10 patients achieved steroid-free remission. The secondary loss of response rate was 15.2%(5/33) .The result of the univariate analysis showed that previous use of glucocorticoids was a risk factor of clinical remission after 14 weeks of VDZ treatment ( χ2=5.88, P=0.015). The result of multivariate logistic regression analysis showed that previous use of glucocorticoids was an independent risk factor of clinical remission after 14 weeks of VDZ treatment ( OR=3.429, 95% confidence interval 1.235 to 9.517, P=0.014). During the follow-up period, 12.3% (10/81) of patients developed Clostridium difficile infections, except for 1 case stopped VDZ treatment because the clinical response was not reached, remaining 9 cases continued VDZ treatment after received anti- Clostridium difficile treatment. Conclusion:VDZ has good clinical efficacy and safety in the treatment of Chinese UC patients, and patients with no history of glucocorticoid use may be more likely to achieve clinical remission after 14 weeks of treatment.

The successful development and application of mRNA COVID-19 vaccine fully illustrated the great potential and application prospect of mRNA technology in the field of biomedicine. Currently, many companies worldwide are developing drugs and vaccines based on mRNA technology for the prevention and treatment of various diseases. It can be foreseen that with the continuous launch of mRNA drugs, commercial GMP production capacity matching them is also urgent. The optimization of production processes, intelligent manufacturing and other risk control strategies, as well as the control of industrialization costs, will help improve the core competitiveness of mRNA innovative drug development. In view of this, this article will provide an overview of the global production process of mRNA drugs and the progress of related GMP production dynamics, sort out the key chain points of the mRNA industry chain, explore the construction of the mRNA pharmaceutical enterprise value chain and the formation of core competitiveness, and provide reference and reference for the research and development of innovative mRNA drugs and high-quality development in China.

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and playimportant role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods: and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identifynew cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

OBJECTIVE: To explore clinical effect of intermittent flap opening technique in L-shaped incision of calcaneal fracture. METHODS: From January 2017 to January 2019, 48 patients with Sanders typeⅡ to Ⅳ calcaneal fractures were treated by open reduction and internal fixation. According to different flap opening techniques, the patients were divided into control group and observation group, 24 patients in each group. In observation group, there were 17 males and 7 females, aged from 20 to 60 years old with an average of(45.12±9.56) years old;7 patients were typeⅡ, 10 patients were type Ⅲ and 7 patients were type Ⅳ according to Sanders classification;3 patients were C0, 16 patients were C1 and 5 patients were C2 according to Tscherne-Gotzen soft-tissue assessment;treated with intermittent flap technique. In control group, there were 19 males and 5 females aged from 20 to 60 years old with an average of (47.32±10.67) years old;7 patients were typeⅡ, 11 patients were type Ⅲ and 6 patients were type Ⅳ according to Sanders classification;2 patients were C0, 18 patients were C1 and 4 patients were C2 according to Tschemc-Gotzen soft-tissue assessment;treated with static flap opening technique. Operation time, flap retraction time, changes of Böhler angle and Gissane angle before and after operation at 3 days, and occurrence of incision complications were observed and compared between two groups. RESULTS: All patients were followed up from 3 to 6 months with an average of(4.52±1.01) months. There were no significant differences in operation time, changes of Böhler angle and Gissane angle before and after operation at 3 days between the two groups(P>0.05);there was statistical difference in flap retraction time between two groups(P<0.05). Occurrence of incision complications in observation group was significantly lower than that in control group (P<0.05). CONCLUSION Intermittent flap opening technique is superior to static opening technique in reducing incision complications of lateral "L" approach of calcaneus. Single Kirschner wire opening does not affect the exposure, reduction and fixation of fracture during operation.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Surgical Wound ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Calcaneus/surgery* ; Ankle Injuries ; Foot Injuries ; Knee Injuries

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Objective　To analyze the survival status and influencing factors among HIV/AIDS transmitted through homosexual contact from 2004 to 2022 in Nan'an District, Chongqing, China. Methods　HIV infected/AIDS patients transmitted through homosexual contact in Nan'an District, Chongqing from 2004 to 2022 were selected for analysis. The survival rate was calculated using the life table method, the median survival time was calculated using the Kaplan-Meier method, and the survival curve was plotted. The Cox regression model was performed to identify factors influencing survival. Results　A total of 3 110 subjects were included in the study, of which 1 199 individuals (38.55%) were transmitted through homosexual contact. The majority of patients were under 30 years old (694, 57.88%), unmarried (917, 76.48%), and had a higher education level of college or above (724, 60.38%), mainly belonging to the Han ethnicity (1 160, 96.75%). Students accounted for 10.43% of occupational status. The majority of patients were initially diagnosed with HIV (1 104, 92.08%), with 71.45% having a CD4+T lymphocyte count >350 cells/μL at the time of initial testing. The primary source of samples was from testing and consultation (52.88%), and the vast majority (93.16%) underwent antiviral treatment. The median survival time for patients transmitted through homosexual contact was 191.45 months, which was higher than 158.37 months of patients transmitted through other routes, demonstrating statistical significance (P<0.001). Multivariate analysis showed that among patients transmitted through homosexual contact, those with CD4+T lymphocyte count≤200 cells/μL had a higher risk of death compared to those with CD4+ T lymphocyte count>350 cells/μL. HIV infected/AIDS patients who did not receive antiviral treatment also had a higher risk of death. Conclusions　From 2004 to 2022, the reported incidence level of HIV/AIDS in Nan'an District showed an overall upward trend, with a slight decrease influenced by respiratory infectious diseases.The risk of death for individuals infected through same-sex transmission routes had not yet been found to be significantly lower than that of other transmission routes, which may be influenced by the late diagnosis time and short follow-up time of individuals infected through same-sex transmission routes.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; Case-Control Studies ; Colorectal Neoplasms/drug therapy* ; Fluorouracil/therapeutic use* ; Humans ; Leucovorin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Prognosis ; Retrospective Studies

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.