Four new triterpenoids, together with six known analogues, were isolated from an aqueous extract of the Ziziphus jujuba var. spinosa seeds, by multiple column chromatographic separation methods using stationary phases of macroporous adsorption resin, MCI resin, normal phase silica gel, Sephadex LH-20, and Toyopearl HW-40C as well as preparative thin-layer chromatography and reversed-phase HPLC. Their structures were determined by spectroscopic data analysis, the new structures were trivially named jujubaceanothoside A (1), 23-epijujuboside A (2), and jujubosides J and K (3 and 4), while the known analogues were identified as jujubosides A-C (5-7) and II (8), alphitolic acid (9), and betulinic acid (10). The structure of 1 was confirmed by single crystal X-ray diffraction.

Objective:To analyze the necessity of anastomosis of the cutaneous nerve by comparing anterolateral femoral flaps with versus without anastomosis of the anterolateral femoral cutaneous nerve in the repair of extremity soft tissue defects.Methods:A retrospective analysis was made of the clinical data of 30 patients with extremity soft tissue defects who had been admitted to Department of Orthopedics, The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University School of Medicine from September 2019 to March 2022. The patients were assigned into 2 groups according to whether the anterolateral femoral cutaneous nerve was anastomosed or not in the repair of extremity soft tissue defects using anterolateral femoral flaps. In the anastomosis groups of 14 cases, there were 7 males and 7 females, with an age of (46.4±15.2) years and a flap size of (22.4±7.3) cm×(8.5±1.3) cm. In the non-anastomosis group of 16 cases, there were 11 males and 5 females, with an age of (39.9±15.8) years and a flap size of (23.0±6.4) cm×(9.0±2.1) cm. The 2 groups were compared in terms of flap survival, Semmes-Weinstein recovery degree and area of monofilament tactile sensation, and time periods for temperature sensation and two-point discrimination.Results:There was no statistically significant difference between the 2 groups in the preoperative general data, showing they were comparable ( P>0.05). All the flaps survived completely without vascular crisis. In the anastomosis group, the time periods required for Semmes-Weinstein recovery of monofilament tactile sensation to the areas of 20.0%, 50.0%, and 80.0% [(2.5±0.7) months, (6.7±1.1) months, and (11.0±1.2) months] were significantly shorter than those in the non-anastomosis group [(3.6±1.3) months, (8.6±1.4) months, and (15.0±2.2) months], the recovery area at the last follow-up [100.0% (100.0%, 100.0%)] was significantly larger than that in the non-anastomosis group [84.6% (81.7%, 89.9%)], and the time period for recovery of temperature sensation [(3.9±0.7) months] significantly shorter than that in the non-anastomosis group [(6.1±1.1) months] (all P<0.05). The time for recovery of two-point discrimination in the 14 patients in the anastomosis group was (10.4±1.7) months while only 7 of the 16 patients in the non-anastomosis group recovered two-point discrimination after (14.7±1.4) months, showing a significant difference between the 2 groups ( P<0.05). Conclusion:In the repair of extremity soft tissue defects using anterolateral femoral flaps, compared with no anastomosis of the cutaneous nerve, anastomosis of the anterolateral femoral cutaneous nerve may ensure more or less the sensory recovery of the flaps.

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

OBJECTIVE: To investigate the biomechanical affect of percutaneous transforaminal endoscopic discectomy(PTED) on adjacent segments with different degrees of degeneration and related risk of adjacent segment diseases (ASD) caused by this operation. METHODS: A healthy male adult volunteer was selected, and the lumbosacral vertebra image data was obtained by CT scan, and the external contour of the bone structure was reconstructed. On this basis, the external contour of the bone structure was fitted by using the smooth curve in 3D-CAD software, and the complete three-dimensional finite element modelof the non degenerate L RESULTS: In the finite element model without adjacent segmental disc degeneration, the annulus fibrosus von Mises stress and intradiscal pressure of the PTED model showed only a slight increase under most stress conditions, and a slight decrease in a few conditions, and there was no significant change trend before and after surgery. In the original degenerated adjacent segment disc model, the biomechanical indicators related to disc degeneration in the pre- and post-PTED model showed significant deterioration, leading to an increased risk of potential adjacent spondylopathy. CONCLUSION PTED surgery will not lead to the significant deterioration of postoperative biomechanical environment of non-degeneration adjacent intervertebral discs, and the original degeneration of adjacent intervertebral discs is a important risk factor for ASD.
Adult ; Biomechanical Phenomena ; Diskectomy, Percutaneous ; Finite Element Analysis ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Range of Motion, Articular

OBJECTIVE: To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously. RESULTS: The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI ( CONCLUSIONS The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.
Cardiac Output ; Child ; Hemodynamics ; Humans ; Hypothermia ; Hypoxia-Ischemia, Brain/therapy* ; Infant ; Infant, Newborn ; Vascular Resistance

Objective:To investigate the relationship between phase behavior of curcumin （CUR） from self-nanoemulsion drug delivery system （SNEDDS） and stability of the formed nanoemulsion in artificial gastrointestinal fluid. Method:The growth rate of precipitation after dispersion of CUR-SNEDDS was expressed by the change tendency of CUR supersaturation-time curve. The effect of drug loading on crystal nucleation and growth was investigated by ultraviolet-visible spectrometry and polarized light microscope， respectively. X-ray powder diffraction （XRD） and differential scanning calorimetry （DSC） were used to analyze the precipitation forms of CUR-SNEDDS with different drug loading in artificial gastrointestinal fluid. At the same time， the effect of drug loading on the quality stability of nanoemulsion formed by CUR-SNEDDS in artificial gastrointestinal fluid was investigated. Result:In the artificial gastrointestinal fluid， with the increase of drug loading， the area under the supersaturation-time curve of CUR was increased （100% drug loading≈90% drug loading>75% drug loading）， the crystallization nucleation and growth rate were accelerated （100% drug loading>90% drug loading>75% drug loading）， the amorphous proportion in the precipitation composition decreased， the nanoemulsion droplets adhered and distributed unevenly， the particle size and dispersivity were increased. Conclusion:High drug loading promotes the nucleation and growth of crystals， and increases the proportion of crystal forms in the precipitation composition， which leads to the decrease in the stability of the formed nanoemulsion. Therefore， it is suggested that the drug loading of CUR-SNEDDS needs to be controlled below 90%.