ObjectiveTo explore the possible mechanism of Qishao Tongbi Capsule （芪芍通痹胶囊， QTC） in the treatment of intervertebral disc degeneration （IDD）. MethodsSeventy-five rats were randomly divided into control group， model group， low-dose QTC group， high-dose QTC group， high-dose QTC +agonist group， with 15 rats in each group. Except for the control group， all other groups were subjected to a fibrous ring puncture to prepare an IDD model. After modeling， rats in low-dose QTC group and high-dose QTC group were given QTC at doses of 0.2 and 0.8 g/（kg·d） by gavage， respectively. Rats in high-dose QTC+ agonist group was given QTC at 0.8 g/（kg·d） and SKL2001 solution at 10 mg/（kg·d） by gavage. The control group and model group were given 10 ml/（kg·d） distilled water by gavage. All treatments were given once a day for 4 consecutive weeks. After treatment， X-ray and magnetic resonance imaging （MRI） were used to detect IDD degree. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were used to observe the morphological changes of the intervertebral disc tissue. Immunohistochemical staining was performed to examine the levels of proteoglycan， type Ⅱ collagen （COL Ⅱ）， and matrix metalloproteinase-3 （MMP-3） in the intervertebral disc tissue. Western blotting was used to detect the extracellular matrix （ECM）-related proteins （proteoglycan， COL Ⅱ， MMP-3， MMP-9， MMP-13）， aging-related proteins （P53， P21， P16）， apoptosis related proteins， including B-cell lymphoma/leukemia 2 （BCL-2）， BCL-2 related X protein （BAX）， Cleaved Caspase-3， and Wnt/β-catenin pathway related proteins such as Wnt3a， glycogen synthase kinase-3β （GSK-3β） and β-catenin in the intervertebral disc nucleus pulposus （NP） tissue. Reverse Transcription Quantitative Polymerase Chain Reaction （RT-qPCR） was used to assess the mRNA expression of Wnt3a， GSK-3β， and β-catenin in intervertebral disc tissue. ResultsCompared with the model group， rats in the low-dose QTC group and high-dose QTC group exhibited improved DHI， decreased Pfirmann grading， and alleviated IDD. The structural integrity of the NP and annulus fibrosus increased， and the number of the NP increased. The levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β increased， while the levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX， Cleaved Caspase-3， Wnt3a and β-catenin protein decreased. The mRNA expression of Wnt3a and β-catenin mRNA decreased， while GSK-3β mRNA expression increased （P＜0.05）. Compared with the low-dose QTC group， the high-dose QTC group showed further improvements in DHI， decrease in Pfirrmann grading （P＜0.05）， and greater alleviation of IDD. The structural integrity of NP and annulus fibrosus was further enhanced， and the number of NP cells further increased. The levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β were higher， while the levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX， Cleaved Caspase-3， Wnt3a and β-catenin were lower. The mRNA expression of Wnt3a and β-catenin decreased， while GSK-3β mRNA expression increased （P＜0.05）. Compared with the high-dose QTC group， the high-dose QTC +agonist group showed a decrease of DHI， an increase of Pfirmann grading （P＜0.05）， significant aggravation of IDD， reduction in structural integrity of the NP and annulus fibrosus， a decrease of NP cell count， lower levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β， and higher levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX and Cleaved Caspase-3. Additionally， GSK-3β mRNA expression decreased （P＜0.05）. ConclusionQTC can inhibit NP cell aging， apoptosis， and ECM degradation in IDD rats， and its therapeutic effect may be mediated through the inhibition of the Wnt/β-catenin pathway.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective: To explore the diagnosis, treatment and prognosis of primary prostatic signet ring cell carcinoma (SRCC), so as to provide reference for the clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with primary prostatic SRCC treated in Nanjing Drum Tower Hospital during Nov.2020 and Sep.2024.The clinical manifestations, imaging features, treatment methods, histological characteristics and prognosis were summarized. Results: The average age of the patients was (72.00±4.28) years.Varying degrees of dysuria occurred in 4 patients. All patients underwent multi-parametric magnetic resonance imaging (mpMRI) examination before surgery, and the results indicated typical prostate cancer.Preoperative biopsies showed high-grade (Gleason 8-10) prostate acinar adenocarcinoma.Postoperative pathological diagnoses were mixed types of prostate acinar adenocarcinoma and SRCC, and no metastasis was found in the pelvic lymph nodes.All patients were followed up for 1 to 46 months after surgery and are currently alive.Robot-assisted laparoscopic radical prostatectomy only was performed in 3 cases; apalutamide and leuprolide/triptorelin was administered after surgery in 2 cases; bicalutamide + goserelin was administered after surgery in 1 case, who developed bladder metastasis of prostate cancer 24 months later, and the serum prostate-specific antigen (PSA) concentration decreased to a safe level (<0.2 ng/mL) after the use of darolutamide with radiotherapy.No recurrence or metastasis was found in the remaining patients. Conclusion: Primary prostatic SRCC is a rare and highly aggressive malignant tumor of the prostate.The diagnosis depends on pathological examinations due to lack of specific imaging features and clinical manifestations.The prognosis is poor, and there is currently no standardized treatment.The combined use of surgery, hormonotherapy and radiotherapy can help improve the survival rate of patients.

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Background Due to the strong sunlight in summer, the temperature on the vehicle deck rises significantly under solar radiation and the internal structures are heated, resulting in prominent heat stress problems in the cabin and seriously affecting the training performance of staff. Objective To study temperature variation patterns inside special vehicle cabins after being exposed to solar radiation, and the quantitative relationship of convection and radiative heat transfer between the vehicle interior environment and the human body, which will provide design reference for further cabin temperature control. Methods Using a solar radiation simulation experimental system, a 6 h exposure experiment was conducted on a special vehicle. The solar radiation intensity from 9:00 to 15:00 on a summer day at an open testing field site was used as the experimental conditions. The tested parameters included temperature on the surface of the vehicle deck (10 points), ambient temperature in the cabin (2 points), near body ambient temperature of testees, radiative heat flux, and total heat flux. Results The temperature of vehicle deck, cabin, and near body increased with the rising solar radiation intensity before 13:30, and then gradually stabilized. The highest temperatures on the vehicle deck and inside the cabin reached 60.5 ℃ and 39.3 ℃, respectively. The highest ambient temperatures of near body for the 4 testees were 41.4 ℃, 41.1 ℃, 41.3 ℃, and 40.8 ℃, respectively, when the humidity inside the cabin was 48.7%. The ratio of radiative heat and convective heat acting on the human body varied over time. The heat transfer between personnel and the vehicle deck and cabin environment mainly exhibited human body heat dissipation until 9:30, when the ratio of radiative heat flux and convective heat flux of the the testees' head/face and chest/abdomen ranged from 1∶4 to 1∶7, and the ratio of the testees' feet was about 1∶3. During 10:00 to 11:00, the human body still exhibited heat dissipation towards the environment, with convective heat dissipation dominating towards the cabin environment, while the vehicle deck gradually began to transform radiative heat towards the human body, when the ratio of radiative heat flux to convective heat flux was 1∶3 to 1∶6. After 11:00, the main heat transfer pattern was from the surrounding environment to the human body, and the ratio of radiative heat flux to convective heat flux was 1∶9 to 1∶12, when the values of radiative heat flux and convective heat flux both significantly increased, and convective heat transfer was dominant. Conclusion The temperature of the special vehicle deck, cabin environment, and near body ambient increases with higher solar radiation intensity. The radiative heat flux and convective heat flux between the cabin environment and the human body gradually increase with the radiation intensity and radiation time, and the quantitative relationship between the two changes with time. Among them, convective heat transfer is always the main heat transfer mode, and the impact of radiative heat transfer on the human body cannot be ignored.

Objective To explore the method and the clinical effect of minimally invasive treating ac-romioclavicular joint dislocation by modified technique bare-handed Tight Rope.Methods A retrospec-tive analysis was performed on 61 cases of acromioclavicular joint dislocation(35 males and 26 fe-males,aged 45.6±5.2 years),treated with minimally invasive internal fixation by modified technique bare-handed Tight Rope between June 2018 and November 2021 in our hospital.According to Tossy classification,21 of them were Tossy Ⅱ and 40 were Tossy Ⅲ.The clinical effect was evaluated by Karlsson criteria,and the shoulder function was assessed by using the Oxford shoulder joint and Con-stant-Murley scores.Results All patients were followed up 9～12 months(11.2 months on the average).Sixty of them were restored without re-dislocation,reaching 60 of excellence and an excellence rate of 98.36％.At the last follow-up,the Constant-Murley and Oxford shoulder joint scores were 95.65±2.32 and 12.92±0.81,both significantly better than before surgery(P<0.01),with the satisfaction rate of 96.74％.Conclusion The treatment of acromioclavicular joint dislocation with modified technique bare-handed Tight Rope is minimally invasive,stable,not easy to relocate,and friendly to acromiocla-vicular joint and subacromial structure.Moreover,the shoulder joint function is well-recovered after the surgery with satisfactory effect.

Objective:To investigate the efficacy of sintilimab combined with paclitaxel and docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Prospective cohort study was performed. A total of 90 patients with advanced NSCLC receiving second-line treatment in Baotou Cancer Hospital from October 2019 to October 2022 were prospectively selected. All patients were divided into the study group (sintilimab combined with paclitaxel and docetaxel as second-line treatment, 45 cases) and the control group (paclitaxel or docetaxel alone, 45 cases) according to random number table method. The short-term efficacy, serum cytokine levels, quality of life and T-cell subsets of the two groups were compared. The survival of patients within 6 months was followed up. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups, and log-rank test was used to make comparison among groups.Results:There were 25 males (55.56%) in the study group with the age of (63±5) years and 28 males (62.22%) in the control group with the age of (65±6) years. There were no statistically significant differences in the gender, age, Eastern Cooperative Oncology Group scores, the body mass (all P>0.05). The total effective rate was 88.89% (40/45) in the study group and 71.11% (32/45) in the control group, and the difference was statistically significant ( χ2 = 4.44, P = 0.035). The levels of serum vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) of both groups after treatment were lower than those before treatment (all P<0.001); the levels of VEGF and CA125 in the study group after treatment were lower than those in the control group [VEGF: (223±15) pg/ml vs. (289±15) pg/ml, t=20.82, P<0.001;CA125: (23±6) ng/ml vs. (75±4) ng/ml, t=51.28, P<0.001].Quality of life scale score, Karnofsky score of both groups after treatment were higher than those before treatment (all P<0.05); quality of life scale score and Karnofsky score in the study group after treatment were higher than those in the control group [quality of life scale score: (63±6) scores vs. (51±5) scores, t=10.29, P<0.001; Karnofsky score: (80.5±5.7) scores vs.(78.8±3.7) scores, t=1.70, P=0.041]. T-cell subsets indicators of both groups after treatment were higher than those before treatment (all P<0.001). T-cell subsets indicators in the study group after treatment were higher than those in the control group [CD3 + cell proportion: (68±5)% vs. (65±5)%, t=2.52, P = 0.014; CD4 + cell proportion:(42.5±1.7)% vs. (36.5±3.7)%, t=9.91, P<0.001;CD4 +/CD8 +: 1.78±0.54 vs. 1.46±0.27, t=3.56, P<0.001]. There was no significant difference in the incidence of adverse reactions between the two groups [11.11% (5/45) vs. 15.55% (7/45), χ2=0.39, P=0.534]. The follow-up time was 6 months. The OS in the study group was better than that in the control group ( χ2=3.86, P = 0.044). Conclusions:Sintilimab combined with taxoid chemotherapy drugs is effective in the second-line treatment of advanced NSCLC, and it improves immune function and shows a favorable safety.

Objective To investigate the clinical effects and pregnancy outcomes of using luteal phase long protocol and GnRH antagonist protocol in patients with polycystic ovary syndrome(PCOS)who have failed their first GnRH antagonist protocol therapy.Methods The clinical data of 163 PCOS patients who underwent IVF/ICSI-ET were retrieved.After the failure of their first GnRH antagonist protocol treatment,they were divided into two groups in the second controlled ovarian hyperstimulation(COH)cycle:Luteal phase long protocol group(n=95)and Gn-RH antagonist protocol group(n=68).A retrospective analysis and comparison of basic clinical data,clinical and laboratory indicators,and pregnancy outcomes between two groups were conducted.Results ① There was no sta-tistically significant difference in basic clinical indicators between two group except LH.② Compared the first and second cycle treatments of patients in the luteal phase long protocol group,the initiation dose of gonadotropin(Gn),total number of Gn days,total Gn usage,estradiol(E2)on the day of hCG injection,number of retrieved eggs,oocyte maturation rate,2PN fertilization rate,2PN cleavage rate,blastocyst formation rate,high-quality blas-tocyst formation rate,and moderate to severe OHSS rate were significantly higher than those in the first GnRH an-tagonist cycle(P＜0.05).The GnRH antagonist protocol group also showed similar improvements.③ The com-parison of the second COH cycle between two groups showed that the total number of Gn days,total Gn usage,and total Gn cost in the luteal phase long protocol group were significantly higher(P＜0.05),while the E2 and LH on the day of hCG injection,and the maturation rate of eggs were significantly lower than those in the GnRH antagonist protocol group(P＜0.05).However,there was no statistically significant difference in the number of retrieved eggs,2PN fertilization,2PN cleavage,blastocyst formation rate,high-quality blastocyst formation rate,and OHSS rate between the two groups;④ The comparison of fresh transplantation cycles for the second COH cycle between the two groups showed that the luteal phase long protocol fresh transplantation rate,implantation rate,clinical preg-nancy rate,and live birth rate were slightly higher than those of the GnRH antagonist protocol group,but the differ-ence was not statistically significant.Comparing the outcomes of pregnancy following the initial frozen-thawed em-bryo transfer(FET)between two groups,the biochemical pregnancy rate and clinical pregnancy rate of the GnRH antagonist protocol group were higher than those of the luteal phase long protocol group(P＜0.05).However,no significant statistical variations were found in implantation rate,live birth rate,neonatal gestational age,and birth weight.Conclusion For PCOS patients who fail the first GnRH antagonist protocol,an appropriate increase in the initiating dose and usage of Gn can achieve satisfactory pregnancy outcomes with both protocols.Compared with change to a luteal phase long protocol,reusing the GnRH antagonist protocol still maintains its long-standing advan-tages,such as shorter total Gn days,lower costs,and better patient compliance.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.