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.

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*

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 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.

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 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.

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.

Objective:To compare the phylotypes of Staphylococcus epidermidis (SE) in skin lesions of acne vulgaris patients versus hair follicles of healthy people, and to analyze their roles in the pathogenesis of acne vulgaris. Methods:A cross-sectional study was conducted from August 2022 to August 2023. Patients with moderate acne vulgaris, as well as healthy volunteers, were enrolled from the Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University. SE strains were isolated from the pustules of acne vulgaris patients and hair follicles of healthy volunteers. Housekeeping genes were amplified by PCR. Sequencing and multilocus sequence typing were performed to compare the phylotypes and genetic relationships of strains from different sources.Results:The acne group consisted of 28 patients (10 males and 18 females) with the age being 22.6 ± 2.6 years, while the healthy group consisted of 19 volunteers (7 males and 12 females) with the age being 22.4 ± 0.96 years. There were no significant differences in age or gender ratio between the two groups (both P > 0.05). The positive rates of SE in the samples of the acne group and the healthy group were 60.71% (17/28) and 73.68% (14/19), respectively, with no significant difference between the two groups ( P = 0.53). The 144 SE strains from the healthy group could be divided into 10 sequence types (STs), and the most common ST was ST35 (8 cases), followed by ST73 (4 cases), ST193 (2 cases), ST59 (2 cases) and ST540 (2 cases) ; 190 SE strains from the acne group could be divided into 16 STs, and the most common STs were ST59 (6 cases) and ST73 (6 cases), followed by ST802 (3 cases), ST130 (3 cases) and ST35 (2 cases). The positive rate of ST35 was significantly lower in the acne group than in the healthy group ( P = 0.018), while there were no significant differences in the positive rates of other STs between the two groups (all P > 0.05). The evolutionary tree analysis showed that the SE strains were mainly distributed in 3 branches. Most of the SE strains from the healthy group belonged to clade A. The proportion of SE strains in clade A ( M[ Q]) was significantly lower in the acne group (25% [85%]) than in the healthy group (100% [33.33%], P = 0.025), while the proportion of SE strains in clade B was significantly higher in the acne group (14.29% [89.17%]) than in the healthy group (0[0], U = 62, P = 0.010), and there was no significant difference in the proportion of SE strains in clade D between the acne group (0 [57.14%]) and healthy group (0[4.17%], P = 0.420) . Conclusion:The phylotypes of SE strains differed between acne vulgaris patients and healthy controls, possibly associated with the occurrence and development of acne vulgaris.

AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.