PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Aim To study the nephrotoxicity effects of the main monomers in Zuojin Pills. Methods CCK-8 and high-content toxicity screening were used to preliminarily screen the main alkaloids in Zuojin Pills that may cause renal cell damage. Further, by confirmation of cell morphology, release rate of lactate dehydrogenase and cytochrome C, and expression of apoptosis-related proteins, the alkaloids causing cell damage were preliminarily identified, providing in vitro toxicological evidence for the compatibility of components of traditional Chinese medicine and compatibility attenuation. Results Preliminary screening using CCK-8 method and high-content technology showed that evodiamine (EVO) could significantly reduce cell number, increase cell membrane permeability, and reduce mitochondrial membrane potential. In addition, cell morphology, apoptosis and cytochrome C expression were consistent with the results of high-content screening. Western blot experiments indicate that EVO could induce apoptosis and cause renal cell damage. Conclusions EVO can obviously cause renal cell damage, and may induce apoptosis by affecting mitochondria, cytochrome C and cell membrane permeability.

Diabetic nephropathy （DN） is one of the serious microvascular complications of diabetes mellitus （DM），and is the main cause of end-stage renal disease（ESRD） worldwide. Although lowering blood glucose and，lowering blood pressure and blocking the renin-angiotensin-aldosterone system（RAAS） can reduce blood glucose，blood pressure and urinary protein to a certain extent，it is still difficult to prevent the progression of DN sometimes. The curative effect of traditional Chinese medicine on DN has been confirmed，but its mechanism is has not been fully clarified. Autophagy is a highly conserved lysosomal degradation pathway in mammals that removes protein aggregates and damaged organelles to maintain cell homeostasis. Podocyte，also known as glomerular epithelial cells，is an important component in maintaining the homeostasis of glomerular filtration barrier，and podocyte injury is considered to be a central link in the occurrence and development of DN. As a highly differentiated cell，podocyte maintains a high level of autophagy to maintain its homeostasis under physiological conditions. In DN state，mammalian target of rapamycin （mTOR），AMP-activated protein kinase （AMPK），silent information regulator 1（SIRT1） and other nutritional signaling pathways as well as intracellular stress response signaling pathways such as oxidative stress，endoplasmic reticulum stress ，and hypoxia stress，etc.，affect podocyte autophagy of podocytes， and ultimately leading to podocyte injury and the progression of DN. In recent years，regulation of podocyte autophagy has become one of the hot spots in DN research，and has also received extensive attention in the field of Chinese medicine. A review and summary of the domestic and international literature in this field reveals that Chinese medicine can affect podocyte autophagy in multiple pathways and targets. Nevertheless， those studiesbut mainly focuses on two nutrient-sensing signaling pathways，mTOR and AMPK，and there lacks more comprehensive and in-depth mechanism studies. In addition，the current research mainly concentrates focuses on the field of Chinese medicine monomers and Chinese medicine compounds，and rarely studies multi-component Chinese medicinelacking research on Chinese medicine component drugs and single drugs，and the research still lacks there is a lack of hierarchy. The regulatory mechanism of Chinese medicine on podocyte autophagy of podocytes in DN state in Chinese medicine still needs to be further studied in depth and systematically.

The normal function of vascular endothelial cells is an important foundation for maintaining vascular permeability， restricting inflammatory activities of the vascular wall， and balancing the coagulation and fibrinolytic system. Endothelial dysfunction caused by persistent damage from pathological factors is considered as an early and prominent event of diabetic macroangiopathy. In traditional Chinese medicine， the classical theory of "restraining excessiveness to acquire harmony" was originally a condensed generalization of the rule of generation， restriction， replacement and evolution in the natural world， revealing the internal regulation mechanism of the stable operation of things. Then it gradually evolved into an important rule to explain the physiological phenomena and pathological mechanism of human body and guide the treatment. Corresponding to the nature， the body homeostasis also requires to achieve a state of strong viscera function and inexhaustible Qi and blood generation under the rule of restriction and generation. The pathogenesis of diabetic macroangiopathy is the process of "the predominant one failing to restrict and the hyperactive one becoming harmful". The loss of restriction and generation of the five organs leads to powerless Qi transformation and， as a result， the Qi， blood and body fluid cannot be dispersed. Therefore， the Qi， blood and body fluid turn into phlegm and blood stasis， such as glucose and lipid metabolism disorder， oxidative stress， inflammatory response and high blood viscosity， and finally block the veins. Excessive phlegm and blood stasis cannot be resolved， instead they become harmful and invade the blood vessel， causing endothelial dysfunction and further resulting in diabetic macroangiopathy. Under the guidance of the theory of "restraining excessiveness to acquire harmony"， the method of "harmonizing viscera， eliminating pathogen and removing turbidity" can effectively regulate the function of vascular endothelial cells， thus playing a positive role in preventing and treating diabetic macroangiopathy. The mechanism may be related to reducing oxidative stress， inhibiting inflammation， limiting vascular smooth muscle proliferation， and reducing platelet adhesion.

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups， Wistar group， model group， Shenqi compound（1.44 g∙kg^-1） group and west glenn（16 mg∙kg^-1） group. After 8 weeks of gavage， the serum insulin（INS） levels were detected by enzyme-linked immunosorbent assay（ELISA）. The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues， the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with blank group， before gavage， 4 weeks， 8 weeks， GK rats have higher blood sugar in each group （P<0.01）.Gavage for 4 weeks and gavage for 8 weeks， compared with model group， the blood sugar of rats in each drug intervention group was lower （P<0.01）. Gavage for 8 weeks， compared with blank group， the INS level of model group was lower （P<0.01）. Compared with model group， the Shenqi compound group had a higher INS level， and the sitagliptin group had a higher INS level （P<0.01）. After gavage for 8 weeks， compared with the blank group， the number of pancreatic islet β-cell apoptosis in the model group was higher （P<0.05）. Compared with model group， the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower （P<0.05，P<0.01）. Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1（PIK3R1） was up-regulated in the Shenqi compound group/model group， and down-regulated in the sitagliptin group/model group， model group/blank group. Protein kinase B1（Akt1） was expressed in the Shenqi compound group/model The expression was up-regulated in the group， sitagliptin group/model group， and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation， can inhibit the islet β cell apoptosis， improve islet β cell function， regulate insulin secretion， and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.