Objective To address the challenges of poor performance and lack of interpretability in existing models,the SHAP algorithm is used to develop an interpretable machine learning model that offers a novel approach to wound age estimation,Methods Based on the previous discovery of the expression of 35 wound age healing-related genes in contused skeletal muscle,the woun age estimaton model was constructed using four algorithms,namly,Multilayer Perceptron(MLP),Random Forest(RF),LightGBM(LGBM),and Support Vector Machine(SVM).The SHAP(Shapley Additive Explanation)algorithm was used to rank the importance of genetic features,eliminate redundant attributes,and optimize the model for accurate wound age estimation.the genetic features of the optimal model were analyzed using SHAP's local interpretation capabilities.Results The best results were obtained using model of MLP(area under the curve(AUC)=0.99)The wound ages were classified into four categories:4～12 h,16～24 h,28～36 h,and 40～48 h,using only 15 gene features.According to SHAP analysis,Fam210a was identified as the most relevant gene.Local analysis revealed that high expression of Fam210a contributed to an increase in the predicted probability of 4 h～12 h,while high expression of Rae1 contributed to an increase in the predicted probability of 16 h～24 h.Additionally,low expression of Tbx18 contributed to an increase in the predicted probability of 28 h～36 h,whereas high expression of Tbx18 contributed to an increase in the predicted probability of 40 h～48 h.Conclusions The combined MLP and SHAP model can be used to predict wound age.Using the SHAP interpreter can better understand the degree of contribution of feature genes to the model prediction,and lay the foundation for further in-depth study of wound age estimation.

Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.
Animals ; Brain Diseases/therapy* ; Xenotropic and Polytropic Retrovirus Receptor ; Brain/pathology*

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.
Female ; Humans ; Progesterone/therapeutic use* ; Qi ; Oligomenorrhea/drug therapy* ; Quality of Life ; Prospective Studies ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Kidney

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

OBJECTIVE: To compare the clinical effect between head acupuncture combined with exercise therapy and conventional acupuncture for nonspecific low back pain. METHODS: A total of 64 patients with nonspecific low back pain were randomized into an observation group (32 cases, 2 cases dropped off) and a control group (32 cases, 2 cases dropped off). In the control group, conventional acupuncture was applied at Jiaji (EX-B 2) of L₁ to L₃, ashi point, Shenshu (BL 23), Dachangshu (BL 25), Yaoyangguan (GV 3) and Weizhong (BL 40). The observation group was treated with head acupuncture combined with exercise therapy, head acupuncture was applied at foot-motor-sensory area on the healthy side and Cuanzhu (BL 2), Tongziliao (GB 1) on the affected side, and McKenzie therapy was performed during retention. The needles were retained for 40 min, once a day, continuous treatment for 6 days with the interval of 1 day, 14 days were required in the two groups. Before and after treatment, the pain visual analogue scale (VAS) score, Oswestry disability index (ODI) score and infrared thermography temperature of pain area in the low back were compared in the two groups. RESULTS: Compared before treatment, the VAS and ODI scores after treatment were decreased in the two groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). Compared before treatment, the infrared thermography temperature of pain area in the low back after treatment was increased in the two groups (P<0.01), and that in the observation group was higher than the control group (P<0.01). CONCLUSION Head acupuncture combined with exercise therapy could relieve pain, improve dysfunction and increase the local temperature of pain area in patients with nonspecific low back pain, and its curative effect is better than conventional acupuncture.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Exercise Therapy ; Humans ; Low Back Pain/therapy* ; Treatment Outcome

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

Objective:Medical post-doctors are important young talents in the field of medical research, to whom the management and training play an important roles in promoting the development of medical research. To improve the academic capacity and training quality of medical post-doctor, this article analyzed the status and problems of post-doctor management, and put forward countermeasures in a grade A tertiary pubic hospital in Beijing.Methods:Questionnaire survey and in-depth interview were used to survey the source, training mode, stress and satisfaction among 17 postdocs from 2016 to 2020.Results:The source of postdocs was limited, and there were a few interdisciplinary postdocs. After scientific research training, many postdocs can significantly improve their scientific research capacity; Most of the postdocs were under great pressure, which is mainly caused by scientific research and economic pressure. Key disciplines and cooperative supervisors are scientific research talents, which have high academic requirements for postdocs. Most postdocs are satisfied with their salary. Cooperative supervisors generally give full play to scientific research and clinical guidance, but lack of mental health guidance; Most postdocs have a low sense of belonging.Conclusions:The article proposed following measurements, including intensity propaganda, strengthen three-level management, enhance the sense of belonging, strengthen the management of cooperative supervisors, pay more attention to psychological counseling, relieve pressure, to improve the scientific research capacity and quality of medical postdocs.

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

The pathological mechanism of allergic rhinitis (AR) involves hierarchically acute and chronic reactions among antigens, immunocytes, immunoglobulins and inflammatory factors. AR, which is characterized by heterogeneity, reacts differently to the current treatment on diverse individuals. Some patients receive unsatisfying clinical outcomes after the treatment. Chinese herbal medicine has become a frequent option to treat AR because it can improve clinical symptoms with excellent safety. The description of Biqiu in ancient Chinese medical literatures is very similar to the clinical manifestation of AR. The major pathogeneses of Biqiu included infection of wind-cold pathogens, deficiency and cold in the lung, and evil depression into heat and wind. Therefore, in modern traditional Chinese medicine （TCM）, Biqiu is considered as an integration of AR, allergic sinusitis and vasomotor rhinitis. According to the pathogenesis and clinical manifestations of Biqiu (including AR), this disease belongs to wind disease in TCM. But modern TCM focuses on deficiency of internal organs and ignores wind evil in syndrome differentiation, contrary to the fact that wind medicine is always used in treating AR. This even leads to an abnormal phenomenon that clinical studies attach little importance to syndrome differentiation. In this paper, we started from the phenomenon that wind medicine is always used in TCM for AR, considering TCM literatures and the study results of modern therapy for wind diseases, and put forward the ideas as follows: AR belongs to exogenous wind disease in TCM, and wind pathogen is the major pathogen, in clinical syndrome differentiation, we should attach more importance to wind evil, and dispelling wind and eliminating dampness is the key to treatment. Meanwhile, based on the fact that most of the classical prescriptions with good effectiveness for AR originated from Treatise on Febrile Disease, mainly including the wind medicines for treating exogenous diseases, it can be inferred that the wind-dispelling and itch-arresting effects of wind medicines are helpful to alleviate or block the allergic reaction of nasal mucus and achieve the goal of relieving itching and sneezing, and the wind-dispelling and dampness-eliminating effects are helpful to alleviate the edema of nasal mucus and achieve the goal of relieving running nose and nasal obstruction. In modern researches, it is also found that classical prescriptions which take wind medicine as a principle component and wind medicine used in AR treatment have good anti-inflammatory, anti-allergic and immune function adjusting effects. This indicates that dispelling wind and eliminating dampness and the wind medicine treatment under its instruction not only correspond to TCM theory, but also have modern science evidences.

Objective To study the distribution of sleep duration in mid－pregnancy women and examine its association with prehypertension ( PHT) ． Methods In the baseline survey of a prospective cohort study，943 women in mid－pregnancy were recruited in Guangzhou，China in 2017－2018． A standardized questionnaire was used to assess demographic characteristics，sleep duration and other lifestyles． We obtained maternal blood pressure values，weights，heights，and medical histories from medical records． Multivariate logistic regression was conducted to examine the association between sleep duration and PHT． Ｒesults The average daily sleep duration of women in mid －pregnancy was ( 10. 41 ± 1. 67 ) hours，and it was negatively related to age and educational level． Overall，98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking． The average night time sleep duration was ( 9. 48±1. 21 ) hours，and it was negatively related to age and educational level． The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours，and it was positively associated with physical activity． The average bedtime was( 22 ∶ 42 ± 1．24) ，and it was positively associated with passive smoking． The prevalence of PHT was 9. 61%． We did not observe any significant association between sleep duration and PHT． Conclusions The mid－pregnancy women in Guangzhou had relatively long sleep duration， and it differed by maternal age，educational level，physical activity，and passive smoking． There was no significant association between sleep duration and PHT．