ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Objective:To explore the clinical efficacy and feasibility of applying a medial plantar vein flap to repair the great toenail flap donor site.Methods:A retrospective analysis was performed on the clinical data of patients who underwent great toenail flap or partial great toenail flap transplantation for finger reconstruction from January 2020 to June 2021 in Longgang Orthopedic Hospital of Shenzhen. During the operation, the donor site of the great toenail flap was repaired with medial plantar venous flaps, and the donor site of the medial plantar venous flaps was repaired with a free full-thickness skin graft. The survival of the flap was observed and the appearance, sensation, and complications of the flap were followed up. The foot function was evaluated by the Maryland foot function evaluation standard.Results:A total of 6 cases were enrolled, including 5 males and 1 female with an average of 22 years, ranged from 14-28 years old. The wound area of the great toenail flap was 2.2 cm×3.7 cm-5.5 cm×7.0 cm, and the skin flap was 2.5 cm×3.8 cm-5.5 cm×7.1 cm. All flaps survived. 2 cases developed tension blisters. All patients were followed up for 3-18 months, with an average of 9 months. And all flaps had no swollen appearance, good color, texture, and no ulcers or pain. Two-point discrimination was 7-10 mm, and the second/third donor area was concealed. According to the Maryland foot function evaluation standard, all 6 cases were rated as excellent.Conclusion:The application of the medial plantar vein flap to repair the donor area of the great toenail flap is an effective repair method. The donor area is concealed, the flap is not bloated, the texture is good, the survival rate is high, and the sensation recovered satisfactory.

Objective:To explore the clinical efficacy and feasibility of applying a medial plantar vein flap to repair the great toenail flap donor site.Methods:A retrospective analysis was performed on the clinical data of patients who underwent great toenail flap or partial great toenail flap transplantation for finger reconstruction from January 2020 to June 2021 in Longgang Orthopedic Hospital of Shenzhen. During the operation, the donor site of the great toenail flap was repaired with medial plantar venous flaps, and the donor site of the medial plantar venous flaps was repaired with a free full-thickness skin graft. The survival of the flap was observed and the appearance, sensation, and complications of the flap were followed up. The foot function was evaluated by the Maryland foot function evaluation standard.Results:A total of 6 cases were enrolled, including 5 males and 1 female with an average of 22 years, ranged from 14-28 years old. The wound area of the great toenail flap was 2.2 cm×3.7 cm-5.5 cm×7.0 cm, and the skin flap was 2.5 cm×3.8 cm-5.5 cm×7.1 cm. All flaps survived. 2 cases developed tension blisters. All patients were followed up for 3-18 months, with an average of 9 months. And all flaps had no swollen appearance, good color, texture, and no ulcers or pain. Two-point discrimination was 7-10 mm, and the second/third donor area was concealed. According to the Maryland foot function evaluation standard, all 6 cases were rated as excellent.Conclusion:The application of the medial plantar vein flap to repair the donor area of the great toenail flap is an effective repair method. The donor area is concealed, the flap is not bloated, the texture is good, the survival rate is high, and the sensation recovered satisfactory.

Objective:To explore the clinical effect of medial plantar venous flow-through flap combined with vein transplantation to repair incomplete finger amputation with circularity soft tissue defect.Methods:A retrospective analysis was performed on the clinical data of patients with incomplete finger amputation injury with circularity soft tissue defect treated by medial plantar venous flow-through flap combined with vein transplantation from January 2016 to October 2020 in Longgang Orthopedic Hospital of Shenzhen. According to the length of the arterial and venous defects of the injured finger and the area of the circular wound, a venous flap (including 2-3 veins )was designed and harvested in the medial plantar. And then two superficial veins were harvested from the donor site to repair the dominant digital artery and distal digital vein of the severed finger. One vein in the flap was bridged to repair the non-dominant digital artery of the severed finger, and the other 1-2 veins were anastomosed with the subcutaneous vein of the proximal wound. The recipient site was closed. The donor site was repaired with full-thickness skin grafting. The appearance, two-point discrimination of the flap, as well as the shape, two-point discrimination, and the extension and flexion of the finger were followed up after the operation. The evaluation was performed by the trial standard for the replantation function of amputated fingers of the Chinese Medical Association Hand Surgery Branch.Results:In this study, a total of 11 patients with thermal crush injury were enrolled, including 7 males and 4 females, aged 16-46 years old. Cyclic skin and soft tissue defect was 1.4 cm×4.5 cm - 3.2 cm×5.4 cm in size after debridement, the arterial defect was 1.6-3.5 cm in length, and the venous defect was 1.7-3.3 cm in length. The flap was 1.6 cm×4.6 cm-3.3 cm×5.5 cm in size, and the harvested vein was 1.7-3.5 cm in length. All severed fingers and flaps survived. Eleven cases were followed up 11-18 months. The appearance of flap was not swollen, and the color and texture were close to the surrounding skin. The two-point discrimination was 7-11 mm. The shape of the finger was good, the two-point discrimination was 5-8 mm, and the extension and flexion activity of the finger was good. Ultimately, the hand function of 10 cases could be rated as excellent, and 1 case could be rated as good. There was slight pigmentation in the donor area, but no ulceration or pain, and no obvious abnormality in wearing shoes, walking, or running.Conclusions:The medial plantar venous flow-through flap combined with vascular transplantation is an ideal repair method to repair incomplete finger amputation with circularity soft tissue defect. It can not only reliably rebuild the blood supply of the distal finger, but also repair the annular defect of the proximal finger. The impact on the donor site is slight.

Objective:To explore the clinical effect of medial plantar venous flow-through flap combined with vein transplantation to repair incomplete finger amputation with circularity soft tissue defect.Methods:A retrospective analysis was performed on the clinical data of patients with incomplete finger amputation injury with circularity soft tissue defect treated by medial plantar venous flow-through flap combined with vein transplantation from January 2016 to October 2020 in Longgang Orthopedic Hospital of Shenzhen. According to the length of the arterial and venous defects of the injured finger and the area of the circular wound, a venous flap (including 2-3 veins )was designed and harvested in the medial plantar. And then two superficial veins were harvested from the donor site to repair the dominant digital artery and distal digital vein of the severed finger. One vein in the flap was bridged to repair the non-dominant digital artery of the severed finger, and the other 1-2 veins were anastomosed with the subcutaneous vein of the proximal wound. The recipient site was closed. The donor site was repaired with full-thickness skin grafting. The appearance, two-point discrimination of the flap, as well as the shape, two-point discrimination, and the extension and flexion of the finger were followed up after the operation. The evaluation was performed by the trial standard for the replantation function of amputated fingers of the Chinese Medical Association Hand Surgery Branch.Results:In this study, a total of 11 patients with thermal crush injury were enrolled, including 7 males and 4 females, aged 16-46 years old. Cyclic skin and soft tissue defect was 1.4 cm×4.5 cm - 3.2 cm×5.4 cm in size after debridement, the arterial defect was 1.6-3.5 cm in length, and the venous defect was 1.7-3.3 cm in length. The flap was 1.6 cm×4.6 cm-3.3 cm×5.5 cm in size, and the harvested vein was 1.7-3.5 cm in length. All severed fingers and flaps survived. Eleven cases were followed up 11-18 months. The appearance of flap was not swollen, and the color and texture were close to the surrounding skin. The two-point discrimination was 7-11 mm. The shape of the finger was good, the two-point discrimination was 5-8 mm, and the extension and flexion activity of the finger was good. Ultimately, the hand function of 10 cases could be rated as excellent, and 1 case could be rated as good. There was slight pigmentation in the donor area, but no ulceration or pain, and no obvious abnormality in wearing shoes, walking, or running.Conclusions:The medial plantar venous flow-through flap combined with vascular transplantation is an ideal repair method to repair incomplete finger amputation with circularity soft tissue defect. It can not only reliably rebuild the blood supply of the distal finger, but also repair the annular defect of the proximal finger. The impact on the donor site is slight.

Objective:To investigate the clinical efficacy and feasibility of anterolateral thigh perforator flap with fascia lata in repairing hand and foot wounds complicated with extensor tendon defect.Methods:The clinical data of patients with hand and foot wounds complicated with extensor tendon defect who were repaired with anterolateral thigh perforator flap with fascia lata in Long Gang District Orthopedic Hospital of Shenzhen from May 2014 to December 2019 were analyzed retrospectively. During the operation, fascia lata was used to repair the defect of extensor tendon.The proximal and distal endof fascia lata were anastomosis with defect extensor tendon by figure 8 sutures.The soft tissue defects of hand and foot were repaired with anterolateral thigh (ALT)perforator flap. The donor site was closed primarily or covered by free skin graft. After operation, the sensory recovery of the flap was evaluated according to the evaluation standard of sensory function after peripheral nerve injury formulated by British Medical Research Association. According to the total active range of movement (TAM) of fingers recommended by the evaluation standard of hand tendon repair of Hand Surgery Society of Chinese Medical Association, the hand motor function was evaluated systematically. Foot motor function was evaluated according to the ankle-hind foot scoring system developed and recommended by the American Association of Foot and Ankle Surgeons.Results:A total of 23 patients were enrolled, including 19 males and 4 females, aged from 9 to 61 years old, with an average age of 26 years old. Causes of injury: there were 11 cases of crushinjury associated with machine, 4 cases of road traffic injury, 6 cases of injury by falling heavy object, 2 cases of saw injury. The area of wound defect ranged from 2 cm × 6 cm to 7 cm × 25 cm, and the length of tendon defect ranged from 1.0 cm to 10.0 cm. All cases were complicated with partial or complete defect of extensor tendon. There were 19 cases with fracture and nerve injury. All the injuries were successfully repaired. All the flaps survived well. The rande of flap harvest was 3 cm × 5 cm to 9 cm × 23 cm, and the fascia lata was 1.0 cm × 1. 5 cm to 4.5 cm × 11. 0 cm. There were no complications such as arteriovenous crisis, infection, fat liquefaction, etc. Andall the wounds were closed primarily. Follow-up period ranged from 3 to 36 months (average 14 months) showed that all flaps had aestheticappearance, good color, and texture. Sensory recovery: excellent in 19 cases and good in 4 cases. TAM system evaluation method and ankle-hind foot scoring system were used to evaluate the function of hand and foot: 21 cases were excellent and 2 cases were good.Conclusions:The application of anterolateral thigh perforator flap with fascia lata to repair the hand and foot wound with extensor tendon defect can restore the motor and sensory function of the injured limb while covering the wound surface.This method has less damage to the donor site and less postoperative complications, and can significantly improve the quality of life of patients. It is an effective method to repair the wounds of hand and footcombined with extensor tendon defect.

Objective:To investigate the clinical efficacy and feasibility of anterolateral thigh perforator flap with fascia lata in repairing hand and foot wounds complicated with extensor tendon defect.Methods:The clinical data of patients with hand and foot wounds complicated with extensor tendon defect who were repaired with anterolateral thigh perforator flap with fascia lata in Long Gang District Orthopedic Hospital of Shenzhen from May 2014 to December 2019 were analyzed retrospectively. During the operation, fascia lata was used to repair the defect of extensor tendon.The proximal and distal endof fascia lata were anastomosis with defect extensor tendon by figure 8 sutures.The soft tissue defects of hand and foot were repaired with anterolateral thigh (ALT)perforator flap. The donor site was closed primarily or covered by free skin graft. After operation, the sensory recovery of the flap was evaluated according to the evaluation standard of sensory function after peripheral nerve injury formulated by British Medical Research Association. According to the total active range of movement (TAM) of fingers recommended by the evaluation standard of hand tendon repair of Hand Surgery Society of Chinese Medical Association, the hand motor function was evaluated systematically. Foot motor function was evaluated according to the ankle-hind foot scoring system developed and recommended by the American Association of Foot and Ankle Surgeons.Results:A total of 23 patients were enrolled, including 19 males and 4 females, aged from 9 to 61 years old, with an average age of 26 years old. Causes of injury: there were 11 cases of crushinjury associated with machine, 4 cases of road traffic injury, 6 cases of injury by falling heavy object, 2 cases of saw injury. The area of wound defect ranged from 2 cm × 6 cm to 7 cm × 25 cm, and the length of tendon defect ranged from 1.0 cm to 10.0 cm. All cases were complicated with partial or complete defect of extensor tendon. There were 19 cases with fracture and nerve injury. All the injuries were successfully repaired. All the flaps survived well. The rande of flap harvest was 3 cm × 5 cm to 9 cm × 23 cm, and the fascia lata was 1.0 cm × 1. 5 cm to 4.5 cm × 11. 0 cm. There were no complications such as arteriovenous crisis, infection, fat liquefaction, etc. Andall the wounds were closed primarily. Follow-up period ranged from 3 to 36 months (average 14 months) showed that all flaps had aestheticappearance, good color, and texture. Sensory recovery: excellent in 19 cases and good in 4 cases. TAM system evaluation method and ankle-hind foot scoring system were used to evaluate the function of hand and foot: 21 cases were excellent and 2 cases were good.Conclusions:The application of anterolateral thigh perforator flap with fascia lata to repair the hand and foot wound with extensor tendon defect can restore the motor and sensory function of the injured limb while covering the wound surface.This method has less damage to the donor site and less postoperative complications, and can significantly improve the quality of life of patients. It is an effective method to repair the wounds of hand and footcombined with extensor tendon defect.