Meta-analysis of neoadjuvant immunotherapy for non-metastatic colorectal cancer.

Background: Immunotherapy has been approved for the treatment of metastatic colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic colorectal cancer remains unclear. We tried to explore clinical effect of neoadjuvant immunotherapy in the treatment of non-metastatic colorectal cancer. Methods: We searched the databases (PubMed, Wanfang Embase, Cochrane Library and China National Knowledge Infrastructure databases) to obtain suitable articles up to September 2022. The primary outcomes of pathological complete response (pCRs), major pathological response (MPR), objective response rate (ORR), R0-resection and anus preserving rate were collected and evaluated. Secordary outcomes (pCRs and MPR) of subgroup analysis between deficient mismatch repair/microsatellite instability-high group (dMMR/MSI-H) and proficient mismatch repair/microsatellite stable group (pMMR/MSS) and outcomes for rectal cancer were analyzed for the final results. Results: We included ten articles and 410 cases of non-metastatic colorectal cancer with neoadjuvant immunotherapy. There were 113 (27.5%) cases with the dMMR/MSI-H status and 167 (40.7%) cases with the pMMR/MSS status. pCRs was found in 167/373 (44.6%) patients (ES: 0.49, 95% CI: 0.36 to 0.62, P<0.01, chi2 = 65.3, P<0.01, I 2 = 86.2%) and MPR was found in 194/304 (63.8%) patients (ES: 0.66, 95% CI: 0.54 to 0.78, P<0.01, chi2 = 42.55, P<0.01, I 2 = 81.2%) with the random-effects model and huge heterogeneity. In the subgroup analysis, pCRs was higher in the dMMR/MSI-H group than the pMMR/MSS group in the fixed-effects model with minimal heterogeneity (OR: 3.55, 95% CI: 1.74 to 7.27, P<0.01, chi2 = 1.86, P=0.6, I 2 = 0%). pCRs was found in 58/172 (33.9%) rectal cancer patients (ES: 0.33, 95% CI: 0.26 to 0.40, P<0.01, chi2 = 3.04, P=0.55, I 2 = 0%) with the fixed-effects model and little heterogeneity. Conclusion: Neoadjuvant immunotherapy could increase pCRs and MPR rate for non-metastatic colorectal cancer. Neoadjuvant immunotherapy could achieve better pCRs rate in dMMR/MSI-H group than in the pMMR/MSS group. Neoadjuvant immunotherapy could be another treatment option for non-metastatic colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42022350523.

Radical treatment of severe open fractures of extremities by orthoplastic surgery: a 10-year retrospective study.

OBJECTIVE: This study aimed to retrospectively analyze clinical data of a series of patients with severe open fractures of extremities (Gustilo IIIb or IIIc), who achieved a satisfactory outcome through radical orthoplastic surgery, so as to provide a reference for determining the treatment of severe open fractures of extremities. METHODS: The clinical data of 41 consecutive patients with severe open fracture (Gustilo IIIb or IIIc) of the limb, who underwent successful surgical debridement, fixation, and soft tissue reconstruction in one stage between January 2008 and January 2019, were retrospectively reviewed. Postoperative indicators, including infection rate and union time, were acquired by a regular follow-up and analyzed. RESULTS: The mean (±SD) age of the patients was 38 ± 16 years. A total of 90 open fractures and severe soft tissue damages were analyzed. The soft tissue cover was achieved within 72 h. The overall rate of infection was 14.6% (6/41). Sex and the Mangled Extremity Severity Score were associated with infection. The median union time of 40 patients (one amputation) was 32 weeks. CONCLUSION: The overall rate of infection exhibited a lower tendency in this study compared with previous studies on high-grade open fractures following a two-stage orthopedic approach. The consequence of infection rate and union time was similar to that in previous studies. These results indicated that the single-stage radical orthoplastic treatment was an effective and reliable option for reconstructing severe open fractures.

Modified human uterus transplantation using ovarian veins for venous drainage: the first report of surgically successful robotic-assisted uterus procurement and follow-up for 12 months.

OBJECTIVE: To report the 12-month results of the first human uterus transplantation case using robot-assisted uterine retrieval. This type of transplantation may become a treatment for permanent uterine factor infertility. DESIGN: Case study. SETTING: University hospital. PATIENT(S): A 22-year-old woman with complete müllerian agenesis who underwent a previous surgery for vaginal reconstruction. The live uterine donor was her mother. INTERVENTION(S): The uterus transplantation procedure consisted of robot-assisted uterine procurement, orthotopic replacement and fixation of the retrieved uterus, revascularization, and end-to-side anastomoses of bilateral hypogastric arteries and ovarian-uterine vein to the bilateral external iliac arteries and veins. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery, and follow-up (12 months). RESULT(S): The duration of the donor and recipient surgeries were 6 and 8 hours, 50 minutes, respectively. No immediate perioperative complications occurred in the recipient or donor. The recipient experienced menarche 40 days after transplant surgery, and she has had 12 menstrual cycles since the surgery. No rejection episodes occurred in the recipient. CONCLUSION(S): These results demonstrate the feasibility of live-donor uterine transplantation with a low-dose immunosuppressive protocol and the role of DaVinci robotic assistance during human uterine procurement. CLINICAL TRIAL REGISTRATION NUMBER: XJZT12Z06.

Osteoprotective effect of cordycepin on estrogen deficiency-induced osteoporosis in vitro and in vivo.

The purpose of this study was to verify the effect of cordycepin on ovariectomized osteopenic rats. Fifty Wistar female rats used were divided into 5 groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with osteopenia, and (3) OVX'd rats with osteopenia treated with cordycepin (5 mg, 10 mg, and 20 mg) for 8 weeks. After the rats were treated orally with cordycepin, serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine (HCY) , C-terminal crosslinked telopeptides of collagen type I (CTX) level, and oxidative stress were examined, respectively. The femoral neck was used for mechanical compression testing. At the same time, we further investigated the effect of cordycepin in vitro assay. The beneficial effects of cordycepin on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, and CTX level. At the same time, cordycepin also increases the OC level in ovariectomized osteopenic rats. The histological examination clearly showed that dietary cordycepin can prevent bone loss caused by estrogen deficiency. These experimental results suggest that complement cordycepin is protective after ovariectomized osteopenic in specific way.

The effects of Cordyceps sinensis phytoestrogen on estrogen deficiency-induced osteoporosis in ovariectomized rats.

BACKGROUND: Isoflavones are naturally occurring plant chemicals belonging to the "phytoestrogen" class. The aim of the present study was to examine the effects of isoflavones obtained from Cordyceps sinensis (CSIF) on development of estrogen deficiency-induced osteoporosis in ovariectomized rats. METHODS: After the rats were treated orally with CSIF, serum alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine (HCY), C-terminal crosslinked telopeptides of collagen type I (CTX), estradiol and interferonγ (IFN-γ) level were examined. At the same time, the urine calcium, plasma calcium, plasma phosphorus and the mass of uterus, thymus and body were also examined. RESULTS: The beneficial effects of CSIF on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, CTX level and IFN-γ level. At the same time, CSIF also increase the OC and estradiol level in ovariectomized osteopenic rats. The histological examination clearly showed that dietary CSIF can prevent bone loss caused by estrogen deficiency. CONCLUSION: The significant estrogenic activity of CSIF demonstrated that CSIF has significant estrogenic effects in OVX rats.

Cordycepin (3'-deoxyadenosine) down-regulates the proinflammatory cytokines in inflammation-induced osteoporosis model.

The effect of cordycepin (3'-deoxyadenosine) on inflammation-induced osteoporosis (IMO) was studied in this paper. After the rats were treated orally with cordycepin (20 mg/kg), serum osteocalcin (OC), homocysteine (HCY), C-terminal cross-linked telopeptides of collagen type I (CTX), maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), they were examined by ELISA or immunohistochemistry. The specimens from the liver were also processed for light microscopic examination. The IMO rats showed a significant increase in plasma CTX, MDA, PMN, IL-1ß, TNF-α, and nitrate levels as well as a significant decrease in plasma OC. These changes were attenuated by cordycepin (20 mg/kg) supplementation in the IMO rats. Examination of the liver specimens revealed mononuclear cell infiltration in the portal areas in the IMO rats which was not detected in the cordycepin (20 mg/kg) rats. These results suggest that cordycepin may act as an anti-inflammatory agent in magnesium silicate-induced inflammation in osteoporosis.

Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

Orthopedic trauma of limbs associated with vascular injuries.

OBJECTIVE: To evaluate the treatment for patients with major vascular injuries associated with traumatic orthopedic injuries. METHODS: A total of 196 patients, aged from 4-67 years with the mean age of 29.88 years, had major vascular injuries associated with traumatic orthopedic injuries and were treated in our hospital in a period of 44 years. The most common mechanism of trauma was blunt trauma (67.3%), open injuries accounted for 32.4% and 54.5% of the injuries were located in the lower extremities. The vascular injury frequently happened in the femoral artery (26.7%) and popliteal artery (20.3%). The treatment principle consisted of aggressive resuscitation, Doppler imaging and stable bone internal fixation with subsequent vascular repair and debridement. The vascular repair for injuries included end-to-end anastomosis (80 cases, 39.6%), interpositional vein graft (94, 46.5%), vascular decompression through fracture distraction (18, 8.9%), arterial ligation (6, 3.0%), vein patch (2, 1.0%), bypass graft (2, 1.0%), venous repair including autogenous vein graft (9, 24.3%) and ligation (28, 75.7%) and prophylactical fasciotomy (15, 7.4%). Postoperative amputation was performed in 16 cases (16.3%). RESULTS: No intraoperative death was observed and all fractures united within 6 months. Limbs were salvaged in 180 patients (91.8%). Among these patients, early complications were found in 19 patients (9.7%) and late complications were observed in 8 patients (4.1%). CONCLUSIONS: A well-organized approach, based on a specific treatment principle, not only improves clinical outcome but also does good to excellent functional recovery for patients with severe orthopedic injuries and concomitant vascular lesion.

[Preparation of rhBMP-2/BCB reconstituted bone xenograft and assay of its osteoinductivity].

OBJECTIVE: To investigate a new grafting material of bone xenograft with strong bone inductive and conductive capacity. METHODS: Based on successful clinical application of the reconstituted bone xenograft (RBX), a new xenograft was made by combining recombinant human bone morphogenetic protein-2 (rhBMP-2) with antigen-free bovine cancellous bone (BCB). Sixty male BALB/C mice aged 4 weeks were divided into study group of 30 and control group of 30 randomly. rhBMP-2/BCB was implanted in the left thigh muscle pouch in the study group and BCB in the control group. The mice were sacrificed at 7 d, 14 d and 21 d after implantation. Inductivity of rhBMP-2/BCB was detected by histological observation and biochemical determination of the samples. RESULTS: Histological examination showed that rhBMP-2/BCB induced chondrogenesis on the 7th day, with woven bone formed on the 14th day, and lamellar bone and marrow on the 21st day, while BCB failed to induce chondrogenesis or osteogenesis on the 7th, 14th and 21st days. The alkaline phosphatase activities and calcium content in study group were higher than those in control group with significant difference (P < 0.01). CONCLUSION: rhBMP-2/BCB is an ideal grafting material with strong bone inductive and conductive capacity without evoking immune reaction.