BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Objective:To compare the efficacy of whole-process visualization system-assisted pedicle screw internal fixation and free-hand pedicle screw internal fixation in the treatment of thoracolumbar burst fracture (TLBF) without neurologic symptoms.Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 patients with TLBF without neurologic symptoms admitted to Zhengzhou Orthopedic Hospital from December 2020 to October 2022, including 41 males and 23 females, aged 23-52 years [(42.1±6.6)years]. The injured vertebrae involved T 11 in 26 patients, T 12 in 17, L 1 in 12, and L 2 in 9. The Wiltse approach was used in all the patients, 31 of whom were treated with pedicle screw internal fixation assisted by the whole-process visualization system (visualization system-assisted screw placement group) and 33 of whom were treated with free-hand pedicle screw internal fixation (free-hand screw placement group). The two groups were compared in terms of operation time, single screw placement time, intraoperative blood loss, intraoperative total radiation dose and total length of hospital stay. The accuracy of pedicle screw placement and penetration rate of the pedicle cortex were evaluated in the two groups. The Cobb angle and lumbar visual analogue scale (VAS) before surgery, at 1 week, 3 months after surgery and at the last follow-up were compared between the two groups. The incidence of postoperative complications was also investigated. Results:All the patients were followed up for 10-33 months [(17.5±4.8)months]. The operation time was (106.9±11.8)minutes in the visualization system-assisted screw placement group, shorter than (121.3±11.4)minutes in the free-hand screw placement group ( P<0.01). The single screw placement time was (9.1±1.0)minutes in the visualization system-assisted screw placement group, shorter than (11.7±1.5)minutes in the free-hand screw placement group ( P<0.01). The total radiation dose was (10.4±2.4)mGy in the visualization system-assisted screw placement group, lower than (51.8±7.2)mGy in the screw placement group ( P<0.01). There was no significant difference in intraoperative blood loss or total length of hospital stay between the two groups ( P>0.05). The accuracy of pedicle screw placement was 96.6% (197/204) in the visualization system-assisted screw placement group, significantly higher than 89.3% (191/214) in the free-hand screw placement group ( P<0.01). Both groups showed significant improvements in Cobb angle and VAS scores at 1 week, 3 months after surgery, and at the last follow-up ( P<0.05). There were no significant differences in Cobb angle or VAS scores between the two groups at each time point ( P>0.05). In the visualization system-assisted screw placement group, one patient had incision infection at 4 days after operation, which was cured with antibiotics. One patient in the free-hand screw placement group developed the symptoms of nerve root irritation at 2 days after surgery, which disappeared at 7 days after revision. There was no significant difference in the incidence of complications between the two groups ( P>0.05). During the follow-up, no patients had broken screws, loosening of internal fixation, or loss of correction in either group. Conclusions:Compared with free-hand pedicle screw internal fixation, the whole-process visualization system-assisted pedicle screw internal fixation in the treatment of TLBF without neurologic symptoms can shorten the time of operation and screw placement, reduce the radiation dose, and improve the accuracy of pedicle screw placement, suggesting that it is a safer and more effective auxiliary method for pedicle screw placement.

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

Objective:To compare the efficacy of whole-process visualization system-assisted pedicle screw internal fixation and free-hand pedicle screw internal fixation in the treatment of thoracolumbar burst fracture (TLBF) without neurologic symptoms.Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 patients with TLBF without neurologic symptoms admitted to Zhengzhou Orthopedic Hospital from December 2020 to October 2022, including 41 males and 23 females, aged 23-52 years [(42.1±6.6)years]. The injured vertebrae involved T 11 in 26 patients, T 12 in 17, L 1 in 12, and L 2 in 9. The Wiltse approach was used in all the patients, 31 of whom were treated with pedicle screw internal fixation assisted by the whole-process visualization system (visualization system-assisted screw placement group) and 33 of whom were treated with free-hand pedicle screw internal fixation (free-hand screw placement group). The two groups were compared in terms of operation time, single screw placement time, intraoperative blood loss, intraoperative total radiation dose and total length of hospital stay. The accuracy of pedicle screw placement and penetration rate of the pedicle cortex were evaluated in the two groups. The Cobb angle and lumbar visual analogue scale (VAS) before surgery, at 1 week, 3 months after surgery and at the last follow-up were compared between the two groups. The incidence of postoperative complications was also investigated. Results:All the patients were followed up for 10-33 months [(17.5±4.8)months]. The operation time was (106.9±11.8)minutes in the visualization system-assisted screw placement group, shorter than (121.3±11.4)minutes in the free-hand screw placement group ( P<0.01). The single screw placement time was (9.1±1.0)minutes in the visualization system-assisted screw placement group, shorter than (11.7±1.5)minutes in the free-hand screw placement group ( P<0.01). The total radiation dose was (10.4±2.4)mGy in the visualization system-assisted screw placement group, lower than (51.8±7.2)mGy in the screw placement group ( P<0.01). There was no significant difference in intraoperative blood loss or total length of hospital stay between the two groups ( P>0.05). The accuracy of pedicle screw placement was 96.6% (197/204) in the visualization system-assisted screw placement group, significantly higher than 89.3% (191/214) in the free-hand screw placement group ( P<0.01). Both groups showed significant improvements in Cobb angle and VAS scores at 1 week, 3 months after surgery, and at the last follow-up ( P<0.05). There were no significant differences in Cobb angle or VAS scores between the two groups at each time point ( P>0.05). In the visualization system-assisted screw placement group, one patient had incision infection at 4 days after operation, which was cured with antibiotics. One patient in the free-hand screw placement group developed the symptoms of nerve root irritation at 2 days after surgery, which disappeared at 7 days after revision. There was no significant difference in the incidence of complications between the two groups ( P>0.05). During the follow-up, no patients had broken screws, loosening of internal fixation, or loss of correction in either group. Conclusions:Compared with free-hand pedicle screw internal fixation, the whole-process visualization system-assisted pedicle screw internal fixation in the treatment of TLBF without neurologic symptoms can shorten the time of operation and screw placement, reduce the radiation dose, and improve the accuracy of pedicle screw placement, suggesting that it is a safer and more effective auxiliary method for pedicle screw placement.