This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

Male ; Humans ; Varicocele/surgery* ; Treatment Outcome ; Abdomen ; Vascular Surgical Procedures ; Microsurgery

Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.

Objective To analyze the overall deployment of Class-A large medical equipments in China.Methods Data of Class A large medical equipments deployed from 2007 to 2015 were collected and classified regionally,for the purpose of measuring the overall deployment,growth level and plan performance.Results There were 403 large medical equipments in China,a rapid rise of deployment,yet still far below developed countries in terms of per capita deployment.Regional differences were significant.With PET-CT as an example,the plan performance in the east(92.19%)was much higher than the west of China(68.57%);plan performance of Class-A equipments was better,conducive to regulating the increase and distribution.Conclusions The deployment level of Class-A equipments in China is low in general,and calls for better regulation regardless of the planning and management progress.

Nine patients with maxillofacial fracture that received intraoperative CT examination in Lanzhou General Hospital of Lanzhou Military Command from January 2017 to March 2017 were retrospectively studied. The procedure of intraoperative CT was introduced. The value of this technique was preliminarily discussed in order to provide a new method for the accurate implementation of maxillofacial fracture surgery.

Objective To explore the intervention effect of yoga combined with music relaxation training on cancer related fatigue in breast cancer patients undergoing chemotherapy.Methods By convenience sampling method,a total of 89 inpatients with breast cancer after chemotherapy in our hospital from June 2015 to June 2016 were selected and were divided into 4 groups by random number table. Patients in the control group (n=23) were given routine nursing care. Based on routine nursing care,patients in experimental group 1 (n=20) received music relaxation training and patients in experimental group 2 (n=24) received yoga training,while patients in experimental group 3 (n=22) received music relaxation training combined with yoga. One month after continuous intervention,cancer fatigue scale (CFS) was applied to measure the degree of fatigue in four groups. Results Before intervention,the fatigue of patients in 4 groups had no difference (P>0.05). After intervention, the scores of CFS in the control group was (25.65±5.79),in experiment group 1 was(22.60±6.75),in experiment group 2 was (22.08±6.57),in experiment group 3 was (21.17±5.53)(F=12.395,P<0.001). The scores of CFS in experiment group 2 and experiment group 3 were statistically decreased compared with those before intervention (t=2.089,2.708;P<0.05).Conclusions Yoga combined with music relaxation training can effectively alleviate the cancer related fatigue of breast cancer patients after chemotherapy,and the curative effect is better than single music training and yoga intervention.

The repair of bone defects poses a great challenge for reconstructive surgeons. Although the development of tissue engineering has exhibited promise in replacing damaged bone, the fabrication of large constructs with functional blood vessels remains an obstacle. From the orthopedic surgeon's point of view, the generation of axially vascularized bone, which can anastomose with the recipient vessel, might be a solution to this medical problem. In this study, we aimed to prefabricate an axially vascularized bone by combining a β-TCP scaffold, arteriovenous loop (AVL), and cell sheet in a bioreactor in vivo. Twelve rabbits were randomly allocated into two groups: the experimental group (presence of AVL) and the control group (absence of AVL). The constructs were explanted at 8 weeks postoperatively. The histomorphometric results showed 42.8±5.9% of the bone area in the AVL group and 26.6±3.5% in the control group. Similarly, vessel analysis revealed the average vessel density in the AVL group (12.5±3.3) was significantly more than that in the control group (6.1±1.5, p<0.05). Our research indicated that the combination of a β-TCP scaffold, AVL and cell sheet might engineer vascularized bone. This prefabrication strategy might facilitate clinical translation of bone tissue engineering in reconstructing large bone defects.
Bioreactors ; Blood Vessels ; Bone and Bones ; Orthopedics ; Rabbits ; Surgeons ; Tissue Engineering

Objective To evaluate the effects of Chuanglingye decoction on angiogenesis and wound healing. Methods With a series of dosages of Chuanglingye decoction, their optimal effects of angiogenesis were searched for through the chicken embryo allantois membrane model(CAM). The vascular endothelial cell proliferation experiment (MTT) and the migration assay were used for the detection of effects. The gauze loading with Chuanglingye decoction of 0.2 ml as the experimental group and with saline of 0.2ml as the control group were applied on the total skin mechanical round wound of 1.5cm diameter and changed every other day. The sizes of area were detected on the day of 0,3,7,14 and 28 as well as the scores of inflammatory response, contains of TNF-αand Il-6 were detected on the day of 3 and 7. Results The CAM experiments showed that the angiogenic effects of 0.2 ml and 0.3 ml dosage of the Chuanglingye group were significantly lower than those of the control group(P<0.05). The 0.2 ml dosage of Chuanglingye decoction was chosen for the further experiment. The HUVEC proliferation rate of the experimental group decreased 21%, as compared with the results of control group. The cell migration movement of 12 hours, 24 hours in the experimental group were significantly lower than those in the control group. For theanimal experiments, the area sizes of the wound were similar in the experimental and control group without any significant differences. The scores of inflammatory response and contains of TNF-α(768±107)ng/L,(380±47)ng/L and Il-6(664±133)ng/L,(363±43)ng/L in the experimental group were significant decreased than those of the control group on the day of 3(958± 140)ng/L,(2215±314)ng/Land 7(512±62)ng/L,(1562±174)ng/L. Conclusion It showed that Chuanglingye decoction had negative effects on vascular endothelial cell migration and proliferation and thus inhibiting angiogenesis. These effects did not infer the process of the wound healing due to its ameliorating the inflammatory response which may be a help to wound healing.

BACKGROUND:Shengji Yuhong col agen showed good curative effect of promoting angiogenesis and tissue healing compared with Shengji Yuhong Gao and col agen alone or gelatin alone.
OBJECTIVE:To explore the curative effect and mechanism of subcutaneous implantation of Shengji Yuhong col agen in rabbits in promoting angiogenesis and repair.
METHODS:Shengji Yuhong col agen as the experimental group and collagen as the control group was implanted inside the rabbit subcutaneous pockets of the back of New Zealand rabbits. The implanted samples and
surrounding tissues were obtained at 3, 7, 14, 28 and 56 days fol owing surgery. Pathological sections were made and the repair of surrounding tissue was observed. Hemoglobin levels in col agen were measured.
Immunofluorescence and CD34 dyeing marking method were utilized to observe capil ary angiogenesis. Western blot assay was employed to examine vascular endothelial growth factor and angiogenin-1 expression.
Immunohistochemistry was used to observe the secretion of typeⅠ and Ⅲ col agen on the surrounding tissues.
RESULTS AND CONCLUSION:The experimental group showed increased subcutaneous vascularization. There were reduced inflammatory exudation, granulation tissue hyperplasia, and mature fiber connective tissue at 28 days.
Angiogenesis and hemoglobin contents were greater in the experimental group than in the control group (P<0.05 or P<0.01). At 3 and 7 days fol owing surgery, vascular endothelial growth factor and angiogenin-1 expression was greater in the experimental group than that in the control group (P<0.05 or P<0.01). The secretion of type Ⅰ col agen was
identical between the experimental and control groups. However, the secretion of type Ⅲ col agen was higher in the experimental group than in the control group at 28 and 56 days (P<0.05), and the proportion of type Ⅰ and Ⅲ
col agen was lower in the experimental group than in the control group at 28 and 56 days (P<0.01). These suggested that Shengji Yuhong col agen can significantly promote angiogenesis in the surrounding tissues with the possible
mechanisms of adjusting the protein expression of vascular endothelial growth factor and angiogenin-1. At the same time, it has the function of regulating col agen formation with better ratio of typeⅠ and type Ⅲ col agen to acquire higher
quality of wound healing with reduced scar formation.