ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease （COPD） with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 （BMAL1） as well as neutrophil extracellular traps （NETs）. MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation， 24 rats were randomly allocated into control group 1， model group 1， midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group， with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide （LPS）. After successful modelling， rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan （LU 9）"， "Feishu （BL 13）" and "Zusanli （ST 36）" during 05：00—07：00， 30 minutes per treatment once every other day for 14 consecutive days （7 sessions in total）. Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours （08：00—18：00）. Pulmonary function parameters including forced expiratory volume in 0.3 second （FEV_0.3）， forced vital capacity （FVC） and FEV_0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin （HE） staining. Plasma levels of pro-inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as pulmonary reactive oxygen species （ROS） content， BMAL1 protein expression and the levels of neutrophil extracellular traps （NETs） biomarkers such as myeloperoxidase （MPO）， neutrophil elastase （NE）， and citrullinated histone H3 （CitH3） in lung tissue were determined. For the mechanistic verification phase， 36 rats were divided into control group 2， model group 2， midnight-noon electro-acupuncture group 2， overexpression empty group， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group， with 6 rats in each group. At the 5th week of model construction， rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally， pulmonary levels of MPO， NE and CitH3 were measured in all groups. ResultsCompared with the control group 1， the model group 1 exhibited decreased FEV_0.3， FVC and FEV_0.3/FVC ratio， elevated plasma IL-1β， TNF-α and pulmonary ROS levels， downregulated lung BMAL1 protein expression， and increased contents of MPO， NE and CitH3 （all P＜0.05）； typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy； HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1， both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators， with superior therapeutic effects in midnight-noon electro-acupuncture group 1 （P＜0.05）. Consistently， midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2， the average optical density of MPO as well as the protein levels of MPO， NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group （P＜0.05）； furthermore， these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 （P＜0.05）. ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.

BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Objective:To comparatively the efficacy of the combined external fixator and the Ilizarov in the treatment of open tibia-fibula fractures and their influence on postoperative infection.Methods:A total of 215 patients with open tibio-fibula fractures diagnosed and treated at Tianjin Medical University General Hospital Airport Site from January 2021 to January 2024 were retrospectively selected as the research subjects. They were divided into the observation group (110 cases, using the combined external frame) and the control group (105 cases, using theIlizarov) according to the types of external fixators adopted. The clinical efficacy, bone healing condition, X-ray callus score, and serological indicators, including the bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF), osteocalcin (OC), C-reactive protein (CRP) in the two groups were compared. The America Orthopedic Foot & Ankle Society(AOFAS) score, Hospital for Special Surgery (HSS) score, and Health Survey Scale (SF-36) score were applied to evaluate the recovery of patients, and the postoperative infection conditions in the two groups were compared.Results:At 12 months after the operation, the excellent and good rate of clinical efficacy in the observation group was higher than that in the control group:90.00%(99/110) vs. 80.00%(84/105), there was statistical difference ( χ2 = 4.24, P<0.05). The complete weight-bearing time, swelling elimination time, bone healing time and postoperative hospital stay in the observation group were shorter than those in the control group:(144.73 ± 15.48) d vs. (152.12 ± 15.55) d, (11.25 ± 1.34) d vs. (13.18 ± 1.37) d, (123.01 ± 12.53) d vs. (136.38 ± 13.45) d, (30.15 ± 3.24) d vs. (31.47 ± 3.48) d, there were statistical differences ( P<0.01). The X-ray callus scores in the observation group at 1 week and 1, 3 and 6 months after the operation were higher than those in the control group: (1.37 ± 0.15) scores vs. (1.28 ± 0.14) scores, (7.65 ± 0.83) scores vs. (5.64 ± 0.75) scores,(12.34 ± 1.25) scores vs. (10.78 ± 1.16) scores,(14.52 ± 1.56) scores vs.(12.11 ± 1.35) scores, there were statistical differences ( P<0.01). Six months after the operation, the levels of BMP-2, VEGF and OC in the observation group were higher than those in the control group: (84.23 ± 8.51) ng/L vs. (76.79 ± 7.82) ng/L, (17.26 ± 1.83) ng/L vs. (15.34 ± 1.67) ng/L, (18.34 ± 1.92) μg/L vs. (6.48 ± 1.75) μg/L; while CRP was lower than that in the control group: (6.49 ± 0.76) mg/L vs. (7.13 ± 0.78) mg/L; there were statistical differences ( P<0.01). The scores of AOFAS, HSS and SF-36 in the observation group at 6 months after the operation were higher than those in the control group: (76.34 ± 7.85) scores vs. (70.11 ± 7.49) scores,(70.12 ± 7.63) scores vs. (67.77 ± 6.68) scores, (93.57 ± 10.34) scores vs. (85.73 ± 8.65) scores, there were statistical differences ( P<0.01 or <0.05). The patients were followed up for 12 months after the operation. There was no statistical difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Compared with the Ilizarov, the combined external fixator has a better therapeutic effect in the treatment of open tibia-fibula fractures. It can promote the healing of bone wounds, improve joint function and quality of life, and has good safety.

The Hedgehog (Hh) signaling pathway is a critical transduction system regulating cell proliferation, differentiation, and tissue homeostasis during embryonic development. Its aberrant activation is closely associated with the pathogenesis of malignancies such as basal cell carcinoma and medulloblastoma. Although Smoothened (SMO)-targeting inhibitors have received clinical approval, their therapeutic efficacy is limited by acquired resistance mutation and compensatory pathway activation. Glioma-associated oncogene homolog 1 (GLI1), the terminal effector transcription factor of the Hh pathway, has emerged as a promising therapeutic target due to its tumor-specific overexpression and lower propensity for resistance induction. However, GLI1 is classified as an "undruggable" target due to the absence of well-defined ligand-binding pockets, low inhibitory activity, and poor drug-like properties. Currently, no GLI1 inhibitor has entered clinical trials. This review systematically analyzes multidimensional modulation strategies (e.g., allosteric modulation, protein-protein interaction disruption, targeted protein degradation) for targeting transcription factors, based on the structural and functional features of GLI1-DNA interaction combined with recent advances in structural biology and chemical biology, offering new paradigms to overcome therapeutic barriers against undruggable targets.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.

Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P＜0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285～5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031～1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P＞0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.

Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P＜0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285～5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031～1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P＞0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.

Objective:To comparatively the efficacy of the combined external fixator and the Ilizarov in the treatment of open tibia-fibula fractures and their influence on postoperative infection.Methods:A total of 215 patients with open tibio-fibula fractures diagnosed and treated at Tianjin Medical University General Hospital Airport Site from January 2021 to January 2024 were retrospectively selected as the research subjects. They were divided into the observation group (110 cases, using the combined external frame) and the control group (105 cases, using theIlizarov) according to the types of external fixators adopted. The clinical efficacy, bone healing condition, X-ray callus score, and serological indicators, including the bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF), osteocalcin (OC), C-reactive protein (CRP) in the two groups were compared. The America Orthopedic Foot & Ankle Society(AOFAS) score, Hospital for Special Surgery (HSS) score, and Health Survey Scale (SF-36) score were applied to evaluate the recovery of patients, and the postoperative infection conditions in the two groups were compared.Results:At 12 months after the operation, the excellent and good rate of clinical efficacy in the observation group was higher than that in the control group:90.00%(99/110) vs. 80.00%(84/105), there was statistical difference ( χ2 = 4.24, P<0.05). The complete weight-bearing time, swelling elimination time, bone healing time and postoperative hospital stay in the observation group were shorter than those in the control group:(144.73 ± 15.48) d vs. (152.12 ± 15.55) d, (11.25 ± 1.34) d vs. (13.18 ± 1.37) d, (123.01 ± 12.53) d vs. (136.38 ± 13.45) d, (30.15 ± 3.24) d vs. (31.47 ± 3.48) d, there were statistical differences ( P<0.01). The X-ray callus scores in the observation group at 1 week and 1, 3 and 6 months after the operation were higher than those in the control group: (1.37 ± 0.15) scores vs. (1.28 ± 0.14) scores, (7.65 ± 0.83) scores vs. (5.64 ± 0.75) scores,(12.34 ± 1.25) scores vs. (10.78 ± 1.16) scores,(14.52 ± 1.56) scores vs.(12.11 ± 1.35) scores, there were statistical differences ( P<0.01). Six months after the operation, the levels of BMP-2, VEGF and OC in the observation group were higher than those in the control group: (84.23 ± 8.51) ng/L vs. (76.79 ± 7.82) ng/L, (17.26 ± 1.83) ng/L vs. (15.34 ± 1.67) ng/L, (18.34 ± 1.92) μg/L vs. (6.48 ± 1.75) μg/L; while CRP was lower than that in the control group: (6.49 ± 0.76) mg/L vs. (7.13 ± 0.78) mg/L; there were statistical differences ( P<0.01). The scores of AOFAS, HSS and SF-36 in the observation group at 6 months after the operation were higher than those in the control group: (76.34 ± 7.85) scores vs. (70.11 ± 7.49) scores,(70.12 ± 7.63) scores vs. (67.77 ± 6.68) scores, (93.57 ± 10.34) scores vs. (85.73 ± 8.65) scores, there were statistical differences ( P<0.01 or <0.05). The patients were followed up for 12 months after the operation. There was no statistical difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Compared with the Ilizarov, the combined external fixator has a better therapeutic effect in the treatment of open tibia-fibula fractures. It can promote the healing of bone wounds, improve joint function and quality of life, and has good safety.

Myopia is becoming more and more common all over the world, and the incidence of myopia is gradually increasing. Many treatments have been used to prevent and control myopia, including optics, drugs, environment or behavior, but the results are different and lack standardization. At present, many experiments have proved that peripheral defocus technology has a certain effect on myopia control. Based on this technology, three kinds of framed eyeglass lenses with peripheral defocus design, namely defocus incorporated multiple segments(DIMS), highly aspherical lenslets(HAL)and cylindrical annular reactive elements(CARE), are commonly used in medical and optometry institutions in China. These lenses provide not only clear vision in the central area, but also a certain amount of myopic defocus in the periphery to control the progression of myopia. This paper aims to focus on the design principle and myopia prevention and control effect of the above three peripheral defocus lenses, and evaluate their effectiveness in clinical practice.

Complete androgen insensitivity syndrome(CAIS) is characterized by lack of androgen response in target organs due to androgen receptor dysfunction, resulting in feminized external genitalia. Individuals with CAIS are typically advised to live as females. This article reports a patient diagnosed with CAIS and gender dysphoria in adulthood. Following the removal of a left pelvic mass, pathology indicated cryptorchidism with a concurrent Leydig cell tumor. Genetic testing revealed a deletion mutation in exon 3 of androgen receptor gene. During follow-up, the patient underwent gender reassignment, transitioning socially from female to male. This case provides new insights into gender allocation for CAIS patients.