Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

Objective To evaluate the effect of a multidisciplinary collaborative quality control management (hereinafter referred to as "QC management") on improving the performance of biological safety cabinets in hospital. Methods A total of 63 ClassⅡbiological safety cabinets in active use at Peking University Third Hospital were selected as the study subjects using the before-after study mode. Conventional management was implemented on the biological safety cabinets from 2018 to 2021. QC management was used in 2022. The compliance of biological safety cabinets management norm and performance differences under the two models were compared. Results The median and the 25th and 75th percentiles [M(P₂₅, P₇₅)] of the service life among these 63 biological safety cabinets were 3 (1,6) years. The overall performance pass rate and inflow velocity pass rate of biological safety cabinets were higher in the QC management than that in the conventional management (90.5% vs 65.1%, 96.8% vs 84.1%, both P<0.05). However, there was no significant difference in downflow velocity, high-efficiency particulate air filter integrity, cleanliness, airflow smoke pattern, noise, and illumination pass rates of biosafety cabinets before and after the implementation of QC management (79.4% vs 88.9%, 90.5% vs 100.0%, 96.8% vs 100.0%, 85.7% vs 100.0%, 100.0% vs 100.0%, and 85.7% vs 96.8%, respectively; all P>0.05). Conclusion sQC management improves the standardization of biological safety cabinet management and key performance indicators in hospital.

Objective To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-related hypophysitis. Methods A retrospective analysis was conducted on patients diagnosed with ICI-related hypophysitis and treated at the Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, between January 2020 and March 2025. Clinical manifestations and prognosis of patients were analyzed. Results Eleven patients with ICI-related hypophysitis were included. The average age was (62.27±7.63) years, and 9 patients (81.82%) were male. The median time to onset was 9.1 months, and the median number of treatment cycles received was 5. The primary initial symptoms were fatigue and anorexia. Hyponatremia was present in 3 patients (27.27%). Evaluation of anterior pituitary function revealed adrenocorticotropic hormone deficiency as the most common manifestation (90.91%, 10/11), followed by hyperprolactinemia (81.82%, 9/11). Posterior pituitary function remained normal in all patients. Pituitary magnetic resonance imaging showed no abnormality in 4 patients (44.44%). Thyroid dysfunction was observed in 6 patients (54.55%), one of whom (9.09%) also exhibited pancreatic endocrine dysfunction. The average follow-up duration was 36.5 months. Eight patients (72.73%) were alive at the last follow-up. None of the patients recovered their pituitary hormone function. Conclusions Endocrine adverse events induced by ICIs can involve multiple glandular systems. Clinicians should be highly vigilant for the possibility of ICI-induced hypophysitis in patients receiving ICIs who present with symptoms such as fatigue, anorexia, and hyponatremia.

In this study, the reductive amination method was used to label IR783 on Astragalus polysaccharides(APS) for the first time, which was verified by ultraviolet-visible spectroscopy and infrared spectroscopy. Quantitative analysis methods of APS-IR783 in plasma and various tissue were established using a multifunctional microplate reader. The pharmacokinetics and tissue distribution of APS-IR783 in mice were investigated after a single intravenous injection of 30 mg·kg~(-1) APS-IR783, and pharmacokinetic parameters were calculated using DAS 2.0 software. The results showed that the APS used had a mass fraction of 93.69%, a relative molecular weight of 1.55×10~5, and a polydispersity index(PDI, M_w/M_n) of 1.73, close to a homogeneous polysaccharide. The IR783 labeling yield reached 86.50%, and the content of IR783 in APS-IR783 was 0.72%. After a single intravenous injection of 30 mg·kg~(-1), the pharmacokinetic parameters of APS in mouse plasma were as follows: T_(max) was(0.67±0.26) h; C_(max) was(1 599.29±159.30) mg·L~(-1); T_(1/2α) and T_(1/2β) were(2.29±3.06) h and(0.44±0.05) h, respectively; AUC_(0-t) was(23 398.91±2 907.03) mg·h·L~(-1); AUC_(0-∞) was(27 710.55±3 506.55) mg·h·L~(-1); MRT_(0-∞) was(34.38±12.59) h; CL was 0.001 L·h~(-1)·kg~(-1); V_z was(0.042±0.017) L·kg~(-1). The in vivo biodistribution study demonstrated that the in vivo exposure ratios of APS in different tissue were in the following order: spleen > liver > kidney > lung > heart > small intestine > muscle > large intestine > brain > stomach, where the top five tissue accounted for 87.54% of the total area under the curve(AUC). This study successfully labeled APS with a water-soluble near-infrared fluorescent probe of IR783 for the first time and revealed the pharmacokinetics and tissue distribution of APS in mice. The paper provides detailed in vivo behavior of APS after intravenous injection, which lays the foundation for the development and utilization of APS and related natural medicines.
Animals ; Mice ; Polysaccharides/chemistry* ; Tissue Distribution ; Astragalus Plant/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Fluorescent Dyes/pharmacokinetics* ; Female

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

OBJECTIVE: To explore early curative effect of upper joint capsule reconstruction combined with biceps tendon transposition in treating irreparable rotator cuff tears. METHODS: From October 2019 to March 2021, 16 patients with irreparable rotator cuff tear were underwent arthroscopic autogenous semitendinosus tendon transplantation for upper articular capsule reconstruction combined with biceps tendon transposition, included 12 males and 4 females, aged from 53 to 72 years old with an average of (62.13±5.35) years old; 3 patients on the left side and 13 patients on the right side. All patients had preoperatively limited joint mobility, resting pain, and mobility pain, and had a history of failure to respond to conservative treatment for more than 8 months. The duration of preoperative symptoms ranged from 45 to 144 months with an average of (85.25±32.08) months. Visual analogue scale (VAS) of shoulder pain, University of California Los Angeles (UCLA) score, Constant-Murley score, active and passive motion of shoulder joint were compared before operation and 2 years after operation, complications were recorded. RESULTS: All 16 patients were followed up for 21 to 32 months with an average of (24.25±3.57) months. There were no complications such as incision infection, vascular and nerve injury, retear occurred. VAS, UCLA and Constant-Murley scores were improved from (5.75±1.18), (11.88±3.38) and (33.38±9.34) before operation to (1.13±0.89), (32.56±2.71), (89.06±6.25) at 2 years after operation (P<0.05). Anterior flexion, abduction, lateral external rotation and lateral internal rotation of shoulder joint were improved from (79.75±21.36) °, (62.06±10.49) °, (19.19±5.41) °, (3.04±0.21) °, respectively to (156.94±13.18) °, (116.19±12.59) °, (42.63±6.07) °, (8.16±0.64) ° at 2 years after operation. Anterior flexion, abduction, lateral lateral rotation and lateral internal rotation of shoulder joint were improved from (116.28±21.47) °, (107.12±9.67) °, (27.62±4.70) °, (4.21±0.41) °, respectively to (165.28±7.15) °, (153.34±4.69) °, (52.46±4.46) °, (9.68±0.68) ° at 2 years after operation, and the difference was statistically significant (P<0.05). CONCLUSION Arthroscopic autograft of semitendinosus tendon combined with transposition of biceps tendon could achieve satisfactory early clinical results in treating patients with irreparable rotator cuff tear, which is a reliable and effective surgical method.
Humans ; Male ; Female ; Middle Aged ; Aged ; Arthroscopy/methods* ; Rotator Cuff Injuries/physiopathology* ; Plastic Surgery Procedures/methods* ; Range of Motion, Articular ; Shoulder Joint/surgery* ; Tendon Transfer

OBJECTIVE: To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits. METHODS: Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage. RESULTS: After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05). CONCLUSION AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals ; Rabbits ; Male ; Transplantation, Autologous ; Cartilage, Articular/injuries* ; Shoulder Dislocation/physiopathology* ; Bone Transplantation ; Shoulder Joint/surgery*

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

OBJECTIVE: To investigate the effects and mechanisms of hydroxysafflor yellow A (HSYA) on replicative senescence in human umbilical cord mesenchymal stem cells (hUC-MSCs). METHODS: hUC-MSCs were cultured to construct a replicative senescence model through continuous amplification in vitro. Cells at passage 2 served as the control group, while cells at passage 10 were designated as the senescence group. The senescent cells were cultured in a culture medium containing HSYA. Cell viability was detected by the CCK-8 assay, and cell confluence was analyzed using the Incucyte S3 live-cell analysis system. The optimal concentration and time point were determined and utilized for subsequent experiments. Senescent cells were pretreated with 0.01 mg/ml HSYA, and the proportion of senescence-associated β-galactosidase (SA-β-gal) positive cells was detected to assess the senescence state. The relative telomere length was detected by qPCR. Reactive oxygen species (ROS) levels were measured using the fluorescent probe DCFH-DA. Mitochondrial membrane potential was assessed by JC-1 staining. The expression of p53, p16, p21, OCT4, and SOX2 genes was detected by qPCR. The expression of p16, p53, OCT4, and SOX2 proteins was analyzed by Western blot. RESULTS: HSYA significantly decreased the SA-β-gal positive staining rate, inhibited telomere attrition, reduced the ROS accumulation, increased mitochondrial membrane potential in senescent cells. Additionally, HSYA downregulated the expression of p53 and p16, and upregulated the expression of OCT4. HSYA decreased p16 protein level and increased OCT4 and SOX2 protein levels. CONCLUSION HSYA may ameliorate replicative senescence in hUC-MSCs by modulating the p53 and p16 signaling pathways and suppressing oxidative stress.
Humans ; Mesenchymal Stem Cells/drug effects* ; Cellular Senescence/drug effects* ; Chalcone/pharmacology* ; Oxidative Stress/drug effects* ; Quinones/pharmacology* ; Umbilical Cord/cytology* ; Reactive Oxygen Species/metabolism* ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Membrane Potential, Mitochondrial ; Cell Proliferation

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China