A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma.

BACKGROUND: NRAS-mutant melanoma is an aggressive subtype with poor prognosis; however, there is no approved targeted therapy to date worldwide. METHODS: We conducted a multicenter, single-arm, phase II, pivotal registrational study that evaluated the efficacy and safety of the MEK inhibitor tunlametinib in patients with unresectable, stage III/IV, NRAS-mutant melanoma (NCT05217303). The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response(DOR), overall survival (OS) and safety. FINDINGS: Between November 2, 2020 and February 11, 2022, a total of 100 patients were enrolled. All (n = 100) patients received at least one dose of tunlametinib (safety analysis set [SAS]) and 95 had central laboratory-confirmed NRAS mutations (full analysis set [FAS]). In the FAS, NRAS mutations were observed at Q61 (78.9%), G12 (15.8%) and G13 (5.3%). The IRRC-assessed ORR was 35.8%, with a median DOR of 6.1 months. The median PFS was 4.2 months, DCR was 72.6% and median OS was 13.7 months. Subgroup analysis showed that in patients who had previously received immunotherapy, the ORR was 40.6%. No treatment-related deaths occurred. INTERPRETATION: Tunlametinib showed promising antitumor activity with a manageable safety profile in patients with advanced NRAS-mutant melanoma, including those who had prior exposure to immunotherapy. The findings warrant further validation in a randomized clinical trial.

Epidemiology and risk factors of nosocomial infections in a Chinese tertiary-care hospital: a 10-year retrospective case-control study.

BACKGROUND: Nosocomial infections (NIs) are the most frequent adverse events among patients and cause a heavy burden on both health and economics. To investigate epidemiology of NIs and identify risk factors for NIs by integrating continuous long-term surveillance data. METHODS: We performed an observational study among inpatients at the Chinese People's Liberation Army General Hospital between January 1, 2010, and December 31, 2019. Infection rates, mortality rates and percentage of NIs were calculated. Trends of yearly infection rates by pathogens were assessed using Mann-Kendall trend test. Controls were matched to cases (2:1) by age (±2 years), sex, admission date (±1 year) and admission diagnosis, and conditional logistic regression was used to estimate odds ratios. RESULTS: A total of 1,534,713 inpatients were included among which 33,468 NIs cases occurred with an infection rate of 2.18%. The most common infections were respiratory system infection (52.22%), bloodstream infection (17.60%), and genitourinary system infection (15.62%). Acinetobacter. baumannii (9.6%), Klebsiella. pneumoniae (9.0%), Pseudomonas. aeruginosa (8.6%), Escherichia. coli (8.6%) and Enterococcus. faecium (5.0%) were the top five isolated pathogens. Infection rates of K. pneumoniae and carbapenems-resistant K. pneumoniae significantly increased. Prior ICU stay, surgery, any device placement (including central venous catheter, mechanical ventilation, urinary catheter, and tracheotomy), prior use of triple or more antibiotics combinations, carbapenem, and ß-Lactamase inhibitors were significantly associated with NIs. CONCLUSION: K. pneumoniae has the potential to cause a clinical crisis with increasing infection rates and carbapenem resistance. Clinical management of invasive operations and antibiotics use should be further strengthened.

Impact of lifestyle and clinical factors on the prognosis of tennis elbow.

Tennis elbow (lateral epicondylitis) typically responds well to conservative treatment, and few patients require surgical intervention. This study aimed to investigate the influence of lifestyle and clinical factors on the prognosis of tennis elbow. This prospective, multicenter, nested case-control study included patients diagnosed with lateral epicondylitis after excluding other conditions. Patients who required surgery because of inadequate improvement after 6 months of conservative treatment were defined as the case group; the remaining patients constituted the control group. Propensity score matching was performed to eliminate baseline differences. Univariate and multivariate analyses were performed using logistic regression. This study included 265 patients (53 in the case group, 212 in the control group). Multivariate analysis revealed that smoking, alcohol consumption, and frequent physical exercise were independent risk factors for surgical intervention, whereas combined treatment with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections was a protective factor against surgery. Subgroup analysis showed that heavy drinkers had a 3.74-fold higher risk of requiring surgical treatment within 1 year than occasional drinkers. Smoking and alcohol consumption were associated with non-operative treatment failure in patients with lateral epicondylitis. Combining oral NSAIDs and corticosteroid injections is a favorable conservative treatment option.

Increasing evolution, prevalence, and outbreaks for rift valley fever virus in the process of breaking geographical barriers.

BACKGROUND: Rift valley fever (RVF) is listed as one of prioritized diseases by WHO. This study aims to describe RVF virus' landscape distribution globally, and to insight dynamics change of its evolution, prevalence, and outbreaks in the process of breaking geographical barriers. METHODS: A systematic literature review and meta-analyses was conducted to estimate RVF prevalence by hosts using a random-effect model. Molecular clock-based phylogenetic analyses were performed to estimate RVF virus nucleotide substitution rates using nucleotide sequences in NCBI database. RVF virus prevalence, nucleotide substitution rates, and outbreaks were compared before and after breaking geographical barriers twice, respectively. RESULTS: RVF virus was reported from 26 kinds of hosts covering 48 countries from 1930 to 2022. Since RVF broke geographical barriers, (1) nucleotide substitution rates significantly increased after firstly spreading out of Africa in 2000, (2) prevalence in humans significantly increased from 1.92 % (95 % CI: 0.86-3.25 %) to 3.03 % (95 % CI: 2.09-4.12 %) after it broke Sahara Desert geographical barriers in 1977, and to 5.24 % (95 % CI: 3.81-6.82 %) after 2000, (3) RVF outbreaks in humans and the number of wildlife hosts presented increasing trends. RVF virus spillover may exist between bats and humans, and accelerate viral substitution rates in humans. During outbreaks, the RVF virus substitution rates accelerated in humans. 60.00 % RVF outbreaks occurred 0-2 months after floods and (or) heavy rainfall. CONCLUSION: RVF has the increasing risk to cause pandemics, and global collaboration on "One Health" is needed to prevent potential pandemics.

Urine immunofixation electrophoresis and serum free light chain analyses benefit diagnosis of multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin.

BACKGROUND: A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients. METHODS: Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department. RESULTS: There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P < .001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B. CONCLUSIONS: Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal.

Investigation on the possibility of dynamic COVID-Zero strategy in China: a population-based transmission model analysis and economic evaluation.

OBJECTIVE: To explore the feasible and cost-effective intervention strategies to achieve the goal of dynamic COVID-Zero in China. DESIGN: A Susceptible-Exposed-Infectious-Recovered model combined economic evaluation was used to generate the number of infections, the time for dynamic COVID-Zero and calculate cost-effectiveness under different intervention strategies. The model simulated the 1 year spread of COVID-19 in mainland China after 100 initial infections were imported. INTERVENTIONS: According to close contact tracing degree from 80% to 100%, close contact tracing time from 2 days to 1 day, isolation time from 14 days to 7 days, scope of nucleic acid testing (NAT) from 10% to 100% and NAT frequency from weekly to every day, 720 scenarios were simulated. OUTCOME MEASURE: Cumulative number of infections (CI), social COVID-Zero duration (SCD), total cost (TC) and incremental cost-effectiveness ratio. RESULTS: 205 of 720 scenarios could achieve the total COVID-Zero since the first case was reported. The fastest and most cost-effective strategy was Scenario 680, in which all close contacts were traced within 1 day, the isolation time was 14 days and 10% of the national population was randomly checked for NAT every day. In Scenario 680, the CI was 280 (100 initial infections) and the SCD was 13 days. The TC was ¥4126 hundred million and the cost of reducing one infection was ¥47 470. However, when the close contact tracing time was 2 days and the degree of close contact tracing was 80%-90%, the SCD would double to 24-101 days and the TCs increased by ¥16 505 to 37 134 hundred million compared with Scenario 680. CONCLUSIONS: If all close contact was controlled within 1 day, the rapid social COVID-Zero can be achieved effectively and cost-effectively. Therefore, the future prevention and control of emerging respiratory infectious diseases can focus on enhancing the ability of close contact tracing.

Effect of e-health interventions on HIV prevention: a protocol of systematic review and meta-analysis.

BACKGROUND: Global epidemiological data indicates that despite implementation of multiple interventions and significant financial investment, the HIV/AIDS epidemic remained inadequately controlled as of 2020. E-health presents a novel approach in delivering health information and health care and has gained popularity in HIV prevention worldwide. However, evidence on the effectiveness of e-health interventions on HIV prevention among diverse populations remains inadequate. Our study aims to systematically evaluate the effectiveness of varying e-health interventions on HIV prevention, with the objective of providing data support and guidance for the development of future e-health HIV intervention strategies. METHODS: A systematic search of electronic English databases, including MEDLINE through PubMed, Embase, Scopus, and Web of Science, along with three Chinese databases, including National Knowledge Infrastructure (CNKI), Chinese Wanfang Digital Periodicals (WANFANG), and Chinese Science and Technology Periodicals (VIP) database, will be conducted for the period of 1 January 1980 to 31 December 2022. Additionally, gray literature and unpublished trials in trial registers will be searched. Studies aimed at HIV prevention through e-health interventions, with full-text publications available in either English or Chinese, will be included. Study types will be limited to RCT, cluster RCT, and quasi-experiment study. The risk of bias in individual studies will be assessed following the guideline highlighted by the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes will cover cognitive, behavioral, psychological, management, and biological measures of individuals involved in e-health interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Ultimately, a systematic review with meta-analysis will be conducted to compare the effectiveness of e-health interventions among diverse populations. DISCUSSION: This systematic review seeks to establish novel insights into the effectiveness of e-health interventions in diverse populations worldwide. It will inform the design and use of e-health interventions to optimize HIV-related strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022295909.

Spatial and temporal distribution of emerging airborne viral infectious diseases outbreaks on a global scale.

Aim: This study aimed to explore the spatial and temporal characteristics of emerging airborne viral infectious diseases outbreaks worldwide. Subject and methods: We conducted a systematic literature review on outbreaks of emerging airborne viral infectious diseases and calculated outbreak number and intensity at the country level. Fisher's exact test was used to compare the viral infectious diseases outbreaks in different income-level regions. To identify the major airborne viral infectious diseases outbreaks, we ranked and extracted the leading viral infectious diseases in outbreak number and intensity in each country by year. Results: A total of 2505 outbreaks were reported from 1873 to 2021 across 2010 studies. There were 47 countries (47/130, 36.15%) with more frequent emerging airborne viral infectious disease outbreaks (more than nine outbreaks), and these countries mainly distributed in high-income regions (22/47 countries, 46.81%, p < 0.05), especially in Western Europe (14/47 countries, 29.79%, p < 0.05). The number of overall outbreaks was more in the United States and China than in other countries in different years. Outbreaks of measles and influenza are always frequent and intense. Highly pathogenic human coronaviruses infection caused short-term pandemics during which their outbreak number and intensity exceeded other viruses. Rift valley fever outbreaks in the human population are spreading outside of Africa through the flow of goods and travelers. Conclusion: Countries in high-income regions reported more emerging airborne viral infectious diseases outbreaks, especially in the Western European region, the United States, and China. It is urgent to strengthen collaborative surveillance of emerging airborne viruses, cross-border flow of goods and travelers, and ecological environment to avoid the spread of viral infectious diseases outbreaks worldwide. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01850-3.

First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.

BACKGROUND: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations. METHODS: This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D. RESULTS: Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months. CONCLUSIONS: The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov number: NCT03973151.

Comparison of the Users' Attitudes Toward Cannabidiol on Social Media Platforms: Topic Modeling Study.

BACKGROUND: As one of the major constituents of the cannabis sativa plant, cannabidiol (CBD) is approved for use in medical treatment and cosmetics because of its potential health benefits. With the rapid growth of the CBD market, customers purchase these products, and relevant discussions are becoming more active on social media. OBJECTIVE: In this study, we aimed to understand the users' attitudes toward CBD products in various countries by conducting text mining on social media in countries with different substance management policies. METHODS: We collected posts from Reddit and Xiaohongshu, conducted topic mining using the latent Dirichlet allocation model, and analyzed the characteristics of topics on different social media. Subsequently, a co-occurrence network of high-frequency keywords was constructed to explore potential relationships among topics. Moreover, we conducted sentiment analysis on the posts' comments and compared users' attitudes toward CBD products on Reddit and Xiaohongshu using chi-square test. RESULTS: CBD-related posts on social media have been rapidly increasing, especially on Xiaohongshu since 2019. A total of 1790 posts from Reddit and 1951 posts from Xiaohongshu were included in the final analysis. The posts on the 2 social media platforms, Reddit and Xiaohongshu, were categorized into 7 and 8 topics, respectively, by the latent Dirichlet allocation model, and these topics on the 2 social media were grouped into 5 themes. Our study showed that the themes on Reddit were mainly related to the therapeutic effects of CBD, whereas the themes on Xiaohongshu concentrated on cosmetics, such as facial masks. Theme 2 (CBD market information) and theme 3 (attitudes toward CBD) on Reddit had more connections with other themes in the co-occurrence network, and theme 3 and theme 1 (CBD therapeutic effects) had a high co-occurrence frequency (22,803/73,865, 30.87%). Meanwhile, theme 1 (CBD cosmetics) on Xiaohongshu had various connections with others (169,961/384,575, 44.19%), and the co-occurrence frequency of theme 4 (CBD ingredients) and theme 1 was relatively prominent (27,128/49,312, 55.01%). Overall, users' comments tended to be positive for CBD-related information on both Reddit and Xiaohongshu, but the percentage was higher on Xiaohongshu (82.25% vs 86.18%; P<.001), especially in cosmetics and medical health care products. CONCLUSIONS: The CBD market has grown rapidly, and the topics related to CBD on social media have become active. There are apparent differences in users' attitudes toward CBD in countries with different substance management policies. Targeted CBD management measures should be formulated to suit the prevalence of CBD use of each country.

Extrapulmonary tuberculosis in China: a national survey.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) is not a notifiable infectious disease in China but is a heavy burden on public health. However, the epidemic situation of EPTB nationwide is unclear. This study aimed to investigate the magnitude and main subtypes of EPTB in China. METHODS: We conducted a national cross-sectional study with multistage, stratified cluster random sampling during 2020-2021. We calculated proportions of EPTB in all patients with TB by organs. Logistic regression models were used to estimate odds ratios by characteristics. RESULTS: A total of 6843 patients with TB were included. Of them, 24.6% were patients with EPTB, and the proportion of EPTB solo was 21.3%. Higher EPTB burden was observed in children, female patients, clinically diagnosed patients, provincial-level and prefectural-level health facilities, and Central and West China. EPTB occurred most frequently in respiratory (35.5%), musculoskeletal (15.8%), and peripheral lymphatic (15.8%) systems with top three subtypes, including tuberculous pleurisy (35.0%), spinal TB (9.8%) and cervical tuberculous lymphadenopathy (7.9%). With the increase of age, proportion of peripheral lymphatic TB decreased, and proportion rank of genitourinary TB rose. CONCLUSION: It is essential to strengthen the diagnosis and treatment capacity for EPTB in primary medical facilities. EPTB should be added to the National Tuberculosis Program as a notifiable disease.

A four-generation family transmission chain of COVID-19 along the China-Myanmar border in October to November 2021.

Background: Foreign imported patients and within-household transmission have been the focus and difficulty of coronavirus disease 2019 (COVID-19) prevention and control, which has also posed challenges to border areas' management. However, household transmission caused by foreign imported cases has not been reported in China's border areas. This study aimed to reveal a clear family clustering transmission chain of COVID-19 caused by contact with Myanmar refugees along the China-Myanmar border during an outbreak in October to November 2021. Methods: During the outbreak, detailed epidemiological investigations were conducted on confirmed patients with COVID-19 and their close contacts in daily activities. Patients were immediately transported to a designated hospital for treatment and quarantine, and their close contacts were quarantined at designated sites. Regular nucleic acid testing and SARS-CoV-2 antibody testing were provided to them. Results: A clear four-generation family clustering transmission involving five patients with COVID-19 was found along the China-Myanmar border. The index case (Patient A) was infected by brief conversations with Myanmar refugees across border fences during work. His wife (Patient B) and 9-month-old daughter (Patient C) were second-generation cases infected by daily contact with him. His 2-year-old daughter (Patient D) was the third-generation case infected by her mother and sister during quarantine in the same room and then transmitted the virus to her grandmother (Patient E, the fourth-generation case) who looked after her after Patients B and C were diagnosed and transported to the hospital. The household secondary attack rate was 80.0%, the average latent period was 4 days, and the generation time was 3 days. Ten of 942 close contacts (1.1%) of this family had positive IgM antibody during the medical observation period. In total 73.9% (696/942) of them were positive for IgG antibody and 8.3% (58/696) had IgG levels over 20 S/CO (optical density of the sample/cut-off value of the reagent). Conclusion: This typical transmission chain indicated that it is essential to strengthen COVID-19 prevention and control in border areas, and explore more effective children care approaches in quarantine sites.

Risks, Epidemics, and Prevention Measures of Infectious Diseases in Major Sports Events: Scoping Review.

BACKGROUND: Major sports events are the focus of the world. However, the gathering of crowds during these events creates huge risks of infectious diseases transmission, posing a significant public health threat. OBJECTIVE: The aim of this study was to systematically review the epidemiological characteristics and prevention measures of infectious diseases at major sports events. METHODS: The procedure of this scoping review followed Arksey and O'Malley's five-step methodological framework. Electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched systematically. The general information (ie, publication year, study type) of each study, sports events' features (ie, date and host location), infectious diseases' epidemiological characteristics (ie, epidemics, risk factors), prevention measures, and surveillance paradigm were extracted, categorized, and summarized. RESULTS: A total of 24,460 articles were retrieved from the databases and 358 studies were included in the final data synthesis based on selection criteria. A rapid growth of studies was found over recent years. The number of studies investigating epidemics and risk factors for sports events increased from 16/254 (6.3%) before 2000 to 201/254 (79.1%) after 2010. Studies focusing on prevention measures of infectious diseases accounted for 85.0% (238/280) of the articles published after 2010. A variety of infectious diseases have been reported, including respiratory tract infection, gastrointestinal infection, vector-borne infection, blood-borne infection, and water-contact infection. Among them, respiratory tract infections were the most concerning diseases (250/358, 69.8%). Besides some routine prevention measures targeted at risk factors of different diseases, strengthening surveillance was highlighted in the literature. The surveillance system appeared to have gone through three stages of development, including manual archiving, network-based systems, and automated intelligent platforms. CONCLUSIONS: This critical summary and collation of previous empirical evidence is meaningful to provide references for holding major sports events. It is essential to improve the surveillance techniques for timely detection of the emergence of epidemics and to improve risk perception in future practice.

Effect of tibial cortex transverse transport in patients with recalcitrant diabetic foot ulcers: A prospective multicenter cohort study.

Background: Management of recalcitrant diabetic foot ulcer (DFU) remains difficult. Distraction osteogenesis mediates new bone formation and angiogenesis in the bone itself and the surrounding tissues. Recently it was reported that tibial cortex transverse transport (TTT) was associated with neovascularization and increased perfusion at the foot in patients with recalcitrant DFUs and facilitated healing and limb salvage. However, the findings were from several single-center studies with relatively small populations, which need to be confirmed in multicenter cohort studies with relatively large populations. Furthermore, the effect of this technique on patient's health-related quality of life is still unclear. Methods: We treated patients with recalcitrant (University of Texas wound grading system 2-C to 3-D and not responding to prior routine conservative and surgical treatments for at least 8 weeks) DFUs from seven centers using TTT (a 5 â€‹cm â€‹× â€‹1.5 â€‹cm corticotomy followed by 4 weeks of medial and lateral distraction) between July 2016 and June 2019. We analyzed ulcer healing, major amputation, recurrence, health-related quality of life (physical and mental component summary scores), and complications in the 2-year follow-up. Foot arterial and perfusion changes were evaluated using computed tomography angiography and perfusion imaging 12 weeks postoperatively. Results: A total of 1175 patients were enrolled. Patients who died (85, 7.2%) or lost to follow-up (18, 1.7%) were excluded, leaving 1072 patients for evaluation. Most of the patients were male (752, 70.1%) and with a mean age of 60.4 â€‹± â€‹9.1 years. The mean ulcer size was 41.0 â€‹± â€‹8.5 â€‹cm2 and 187 (16.6%) ulcers extended above the ankle. During the follow-up, 1019 (94.9%) patients healed in a mean time of 12.4 â€‹± â€‹5.6 weeks, 53 (4.9%) had major amputations, and 33 (3.1%) experienced recurrences. Compared to preoperatively, the patients had higher physical (26.2 â€‹± â€‹8.3 versus 41.3 â€‹± â€‹10.6, p â€‹= â€‹0.008) and mental (33.6 â€‹± â€‹10.7 versus 45.4 â€‹± â€‹11.3, p â€‹= â€‹0.031) component summary scores at the 2-year follow-up. Closed tibial fracture at the corticotomy site was found in 8 (0.7%) patients and was treated using external fixation and healed uneventfully. There were 23 (2.1%) patients who had pin site infections and were treated successfully with dressing changes. Compared to preoperatively, the patients had more small arteries and higher foot blood flow (8.1 â€‹± â€‹2.2 versus 28.3 â€‹± â€‹3.9 ml/100 â€‹g/min, p â€‹= â€‹0.003) and volume (1.5 â€‹± â€‹0.3 versus 2.7 â€‹± â€‹0.4 ml/100 â€‹g, p â€‹= â€‹0.037) 12 weeks postoperatively. Conclusion: TTT promotes healing, limb salvage, and health-related quality of life in patients with recalcitrant DFUs as demonstrated in this multicenter cohort study. The surgical procedure was simple and straightforward and the complications were few and minor. The effect of this technique was associated with neovascularization and improved perfusion at the foot mediated by the cortex distraction. The findings are required to confirm in randomized controlled trials.The Translational Potential of this Article: TTT can be used as an effective treatment in patients with recalcitrant DFUs. The mechanism is associated with neovascularization and consequently increased perfusion in the foot after operation.

COVID-19 Vaccination Rates of People Who Use Drugs - Chengdu City, Sichuan Province, China, November 2021 - February 2022.

What is already known about this topic?: Few studies have reported that people who use drugs (PWUDs) have much lower coronavirus disease 2019 (COVID-19) vaccination rates than the general population, especially with no relative information reported in China specifically. What is added by this report?: This study seminally uncovers that the vaccination rate among PWUDs was about 79.34% in one district of Chengdu City, Sichuan Province, China. Assuming that unvaccinated PWUDs with disease records were really not eligible for vaccination, the vaccination rate goes up to 87.25% among the studied PWUDs. The study implies that PWUDs were not left behind in the vaccination drive against COVID-19 in China. What are the implications for public health practice?: In pandemics like COVID-19, government leadership and the overall planning and distribution of public health products are critical in achieving national health equity. However, in order to do this as well as avoid discrimination or exclusion among specific portions of the general population, it's necessary to understand the vaccination rates and behaviors of at-risk groups such as PWUD's.

Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein in Diagnosis of Malignant Tumors.

BACKGROUND: To assess the potential of AFP-L3% for the utility to diagnose malignant tumors. METHODS: AFP-L3 was concentrated from clinically-collected serum samples via the Hotgen Biotech glycosyl capture spin columns and then measured through the protein microarrays. The levels of AFP and AFP-L3 were detected by electrochemiluminescence immunoassay. In this retrospective study, 266 patients with the level of serum AFP-L3 over 1 ng/mL were recruited from December 2014 through April 2019. Among them, 155 patients were clinically diagnosed/confirmed with malignant tumors, including 101 hepatocellular carcinomas, 47 stomach malignant tumors, and 7 other malignant tumors; and the rest of 111 patients were nonmalignant tumors. RESULTS: Patients with serum AFP-L3 level of greater than 1 ng/mL were mainly detected in hepatic diseases, including hepatocellular carcinoma, cirrhosis and chronic hepatitis. In patients with no tumors, the levels of serum AFP-L3 over 1 ng/mL were only observed in liver disease. The levels of AFP-L3 in blood were substantially greater in patients with HCC. Among the malignant tumor patients with the level of serum AFP-L3 over 1 ng/mL, HCC accounted for 60%, gastric cancer for nearly 40%. The AFP, AFP-L3, and AFP-L3% in blood were increased significantly in patients with liver malignancy, chronic liver disease, and cirrhosis. However, the elevation of AFP-L3 and AFP-L3% in the malignant cohort was more evident than that in the nonmalignant counterpart. CONCLUSIONS: AFP-L3 is likely to contribute to the differential diagnosis of HCC as well as other hepatic diseases. AFP-L3% is a reliable indicator for diagnosing benign and malignant tumors.

Epidemiological and clinical characteristics of the largest COVID-19 outbreak along the China-Myanmar border in Ruili City, Yunnan Province, China.

Background: Imported COVID-19 patients posed great challenges to border areas' COVID-19 control. However, research was scarce to reveal epidemiological characteristics of COVID-19 in border areas. This study aimed to explore the detailed transmission chains, and reveal epidemiological and clinical characteristics of the largest COVID-19 outbreak caused by Delta variant of concern (VOC) occurred in the China-Myanmar border area. Methods: During the outbreak from July to September, 2021 in Ruili City, Yunnan Province, China, epidemiological investigation data and clinical-related data pertaining to confirmed COVID-19 patients were collected. Patients' contact history data and viral gene sequencing were used for inference of transmission chains. Sociodemographic and epidemiological characteristics, cycle threshold (Ct) value, and antibodies level were compared between patients who were vaccinated against COVID-19 or not. Results: A total of 117 COVID-19 patients were confirmed during the outbreak, among which 86 (73.5%) were breakthrough infections. These patients evenly split between Chinese and Myanmar people (50.4% vs. 49.6%). Most of these patients were mild (45.3%) or moderate (48.7%) infections with no death reported. Multi-source of infection led to 16 transmission chains with a maximum of 45 patients in one chain. Patients vaccinated against COVID-19 before infection had relatively higher antibodies (IgM and IgG) levels and more rapid response to infection than non-vaccinated patients (p < 0.05). Conclusion: Land border areas have greater risks of imported COVID-19 and more complicated epidemics. It should be cautious in formulating entry and exit requirements for border areas. The immune effect of COVID-19 vaccines and related mechanism should be further explored.

Trends in Methamphetamine Use in the Mainland of China, 2006-2015.

Background: Methamphetamine is the most prevalent drug in the mainland of China, yet few studies on the non-medical use of methamphetamine nationwide have been conducted. This study aimed to examine the trends in the prevalence of non-medical methamphetamine use and to explore the flow pattern of internal migrant methamphetamine users in the mainland of China. Methods: Data were extracted from the National Dynamic Management and Control Database for Drug Users (NDMCD). Joinpoint regressions were used to examine trends in the prevalence and population size of methamphetamine use. Results: A total of 1,821,468 methamphetamine use cases registered in NDMCD from 2006 to 2015 were identified. The number of methamphetamine use cases presented an increasing trend in all age subgroups, and among them, the elderly increased the fastest [annual percent change (APC2006-2015), 122.9; 95% CI, 113.0-133.3; p < 0.001]. The prevalence of methamphetamine use increased from 4.69 per 100,000 population in 2008 to 45.38 per 100,000 population in 2015 (APC2008-2015, 36.1; 95% CI, 31.9-40.6; p < 0.001). The regions of the Pearl River Delta, Yangtze River Delta, and Beijing-Tianjin-Hebei Urban Agglomeration absorbed over 96% of all internal migrant methamphetamine use cases, and the number of migrant methamphetamine use cases presented increased trends in these three regions. Conclusions: The increasing trends in methamphetamine use have become a threat to all age groups in China. Substance use prevention programs should focus on internal migrant drug users, especially in economically developed regions.