ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Objective To analyze the changes in the respiratory characteristics of the upper respiratory tract under nasal obstruction conditions,to identify the disparities in the flow-heat transfer processes within the respiratory tract,and to provide auxiliary support for the diagnosis and treatment of respiratory diseases.Methods We established in this study a three-dimensional(3-D)model of the human upper respiratory tract based on computed tomography(CT)data.Computational fluid dynamics methods were used to compare and analyze the flow and heat transfer characteristics of the human upper respiratory tract under normal breathing and nasal obstructive conditions.Results During normal breathing,the complex geometric shapes and large areas of heat transfer inside the nasal cavity of humans allowed the respiratory airflow in the posterior part of the nasal cavity to be warmed close to the body temperature.Under unilateral nasal obstruction,relatively high-speed gas and low-speed gas quickly mixed up and homogenized in the posterior part of the nasal cavity,and the airflow underwent sufficient heat transfer in the nasal cavity.Under bilateral nasal obstruction,air was inhaled through the mouth,and the flow velocity was significantly higher at the nasopharynx and the airway entrance compared to that of normal nasal air intake.Moreover,the heat transfer intensity of the airflow in the oral cavity was relatively weak,and the temperature rise of the airflow in the oral cavity was relatively small.Conclusion A stable nasal breathing pattern plays an important role in maintaining human respiratory comfort and preventing respiratory diseases.

Objective:To investigate the efficacy of percutaneous vertebroplasty through unilateral transverse process-pedicular for postmenopausal lumbar osteoporotic fractures.Methods:Retrospective analysis included 102 patients with postmenopausal lumbar osteoporotic fracture admitted to Hangzhou Fuyang Hospital of Orthopedics of Traditional Chinese Medicine from Jan. 2023 to Jan. 2024, who were divided into unilateral transverse process-pedicular group (UTPP group, n=48) and unilateral transverse pedicular group (UTP group, n=54) by means of approach. The changes of surgery-related indexes, imaging indexes and postoperative lumbar function recovery of the two groups were observed, and the patients were followed up for 1 year to record the incidence of secondary fracture of injured vertebra, fracture of adjacent vertebra and diffusion of bone cement. Results:The bone cement leakage rate in UTPP group was lower than that in UTP group ( P < 0.05), and there was no statsistically significant difference in operation time, fluoroscopy times, intraoperative blood loss, bone cement injection amount and hospital stay between the two groups ( P > 0.05). Before surgery, 3 months and 6 months after surgery, vertebral anterior margin height, middle vertebral height and sagittal cobb Angle between the two groups showed no significant differences ( P > 0.05). Visual analogue score (VAS) and oswestry disability index (ODI) between the two groups before surgery and 3 months after surgery had no statistically significant differences ( P > 0.05) ; VAS and ODI scores in UTPP group were lower than those in UTP group 6 months after surgery ( P < 0.05). The incidence of secondary fracture in UTPP group was lower than that in UTP group, while the height diffusion rate of bone cement was higher (all P < 0.05). The incidence of adjacent vertebral fracture between the two groups showed no statistically significant difference ( P > 0.05) . Conclusions:In postmenopausal patients with lumbar osteoporotic fractures, percutaneous vertebroplasty through unilateral transverse process-pedicular can effectively reduce the rate of intraoperative bone cement leakage, and has certain advantages in improving postoperative pain, promoting the recovery of postoperative lumbar function and reducing the risk of secondary fractures.

Objective:To investigate the clinical effectiveness of Du Meridian moxibustion combined with brisk walking on negative symptoms, cognitive function, and social function in patients with stable schizophrenia, aiming to provide a feasible adjunctive treatment for clinical practice.Methods:A randomized controlled trial was conducted using convenience sampling to recruit 140 patients with stable schizophrenia hospitalized at the Affiliated Brain Hospital of Guangzhou Medical University from April 1, 2023, to March 31, 2024. Patients were randomly assigned to a control group, Du Meridian moxibustion group, brisk walking group, or combined group, with 35 patients in each group. The control group received standard care. On this basis, the Du Meridian moxibustion group received moxibustion on the Du Meridian, the brisk walking group participated in slow walking exercises, and the combined group received both interventions for 12 weeks. Assessments were conducted at baseline, at 6 and 12 weeks during the intervention, and at 12 weeks post-intervention using the Scale for the Assessment of Negative Symptoms, Mini-Mental State Examination, and Social Functioning Scale for Inpatient Psychiatric Patients.Results:A total of 134 patients completed the study: control group ( n = 34), Du Meridian moxibustion group ( n = 34), brisk walking group ( n = 35), and combined group ( n = 31). The combined group demonstrated significantly lower SANS scores at the 12th week of intervention (49.71 ± 4.66) and at 12 weeks post-intervention (53.45 ± 5.34) compared to the Du Meridian moxibustion group (54.91 ± 4.79) and (59.56 ± 5.84), the brisk walking group (56.69 ± 5.59) and (58.51 ± 5.42), control group (65.71 ± 4.95) and (66.21 ± 4.33), with statistically significant differences ( t values were 3.81-13.37, all P<0.05). Regarding cognitive function, the MMSE scores in the combined group at the 12th week of intervention (28.23 ± 1.28) and at 12 weeks post-intervention (27.35 ± 1.76) were higher than those in the Du Meridian moxibustion group (26.79 ± 1.85) and (25.59 ± 2.27) and the brisk walking group (25.88 ± 2.23) and (25.43 ± 1.84), control group (23.65 ± 2.17) and (22.32 ± 2.14), with statistically significant differences ( t values were - 10.28 to - 3.48, all P<0.001). For social function, the SSPI scores in the combined group at the 12th week of intervention (35.71 ± 3.63) and at 12 weeks post-intervention (32.58 ± 3.71) were also significantly higher than those in the Du Meridian moxibustion group (32.21 ± 3.91) and (28.47 ± 3.70) and the brisk walking group (31.83 ± 3.54) and (30.31 ± 3.59), control group (24.53 ± 4.12) and (24.15 ± 3.50) with statistically significant differences ( t values were - 11.56 to - 2.52, all P<0.05). Conclusions:The combination of Du Meridian moxibustion and brisk walking is an effective adjunctive intervention for patients with stable schizophrenia, as it significantly reduces negative symptoms, enhances cognitive function, and improves social functioning.

Objective:To investigate the efficacy of percutaneous vertebroplasty through unilateral transverse process-pedicular for postmenopausal lumbar osteoporotic fractures.Methods:Retrospective analysis included 102 patients with postmenopausal lumbar osteoporotic fracture admitted to Hangzhou Fuyang Hospital of Orthopedics of Traditional Chinese Medicine from Jan. 2023 to Jan. 2024, who were divided into unilateral transverse process-pedicular group (UTPP group, n=48) and unilateral transverse pedicular group (UTP group, n=54) by means of approach. The changes of surgery-related indexes, imaging indexes and postoperative lumbar function recovery of the two groups were observed, and the patients were followed up for 1 year to record the incidence of secondary fracture of injured vertebra, fracture of adjacent vertebra and diffusion of bone cement. Results:The bone cement leakage rate in UTPP group was lower than that in UTP group ( P < 0.05), and there was no statsistically significant difference in operation time, fluoroscopy times, intraoperative blood loss, bone cement injection amount and hospital stay between the two groups ( P > 0.05). Before surgery, 3 months and 6 months after surgery, vertebral anterior margin height, middle vertebral height and sagittal cobb Angle between the two groups showed no significant differences ( P > 0.05). Visual analogue score (VAS) and oswestry disability index (ODI) between the two groups before surgery and 3 months after surgery had no statistically significant differences ( P > 0.05) ; VAS and ODI scores in UTPP group were lower than those in UTP group 6 months after surgery ( P < 0.05). The incidence of secondary fracture in UTPP group was lower than that in UTP group, while the height diffusion rate of bone cement was higher (all P < 0.05). The incidence of adjacent vertebral fracture between the two groups showed no statistically significant difference ( P > 0.05) . Conclusions:In postmenopausal patients with lumbar osteoporotic fractures, percutaneous vertebroplasty through unilateral transverse process-pedicular can effectively reduce the rate of intraoperative bone cement leakage, and has certain advantages in improving postoperative pain, promoting the recovery of postoperative lumbar function and reducing the risk of secondary fractures.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Objective:To investigate the clinical effectiveness of Du Meridian moxibustion combined with brisk walking on negative symptoms, cognitive function, and social function in patients with stable schizophrenia, aiming to provide a feasible adjunctive treatment for clinical practice.Methods:A randomized controlled trial was conducted using convenience sampling to recruit 140 patients with stable schizophrenia hospitalized at the Affiliated Brain Hospital of Guangzhou Medical University from April 1, 2023, to March 31, 2024. Patients were randomly assigned to a control group, Du Meridian moxibustion group, brisk walking group, or combined group, with 35 patients in each group. The control group received standard care. On this basis, the Du Meridian moxibustion group received moxibustion on the Du Meridian, the brisk walking group participated in slow walking exercises, and the combined group received both interventions for 12 weeks. Assessments were conducted at baseline, at 6 and 12 weeks during the intervention, and at 12 weeks post-intervention using the Scale for the Assessment of Negative Symptoms, Mini-Mental State Examination, and Social Functioning Scale for Inpatient Psychiatric Patients.Results:A total of 134 patients completed the study: control group ( n = 34), Du Meridian moxibustion group ( n = 34), brisk walking group ( n = 35), and combined group ( n = 31). The combined group demonstrated significantly lower SANS scores at the 12th week of intervention (49.71 ± 4.66) and at 12 weeks post-intervention (53.45 ± 5.34) compared to the Du Meridian moxibustion group (54.91 ± 4.79) and (59.56 ± 5.84), the brisk walking group (56.69 ± 5.59) and (58.51 ± 5.42), control group (65.71 ± 4.95) and (66.21 ± 4.33), with statistically significant differences ( t values were 3.81-13.37, all P<0.05). Regarding cognitive function, the MMSE scores in the combined group at the 12th week of intervention (28.23 ± 1.28) and at 12 weeks post-intervention (27.35 ± 1.76) were higher than those in the Du Meridian moxibustion group (26.79 ± 1.85) and (25.59 ± 2.27) and the brisk walking group (25.88 ± 2.23) and (25.43 ± 1.84), control group (23.65 ± 2.17) and (22.32 ± 2.14), with statistically significant differences ( t values were - 10.28 to - 3.48, all P<0.001). For social function, the SSPI scores in the combined group at the 12th week of intervention (35.71 ± 3.63) and at 12 weeks post-intervention (32.58 ± 3.71) were also significantly higher than those in the Du Meridian moxibustion group (32.21 ± 3.91) and (28.47 ± 3.70) and the brisk walking group (31.83 ± 3.54) and (30.31 ± 3.59), control group (24.53 ± 4.12) and (24.15 ± 3.50) with statistically significant differences ( t values were - 11.56 to - 2.52, all P<0.05). Conclusions:The combination of Du Meridian moxibustion and brisk walking is an effective adjunctive intervention for patients with stable schizophrenia, as it significantly reduces negative symptoms, enhances cognitive function, and improves social functioning.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.