Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective To explore the value of MR T2WI-spectral attenuated inversion recovery(T2WI-SPAIR)sequence and dif-fusion tensor imaging(DTI)in the recovery process of vertebral compression fractures over time.Methods Three patients aged 60-75 years with a clear time and mechanism of injury were selected.They underwent conventional MR sequences and DTI scans at eight time points.The morphological and signal changes of the fractured vertebrae on T2WI-SPAIR sequences were dynamically observed.Statistical analysis was performed on the apparent diffusion coefficient(ADC)and fractional anisotropy(FA)of the fractured verte-brae and adjacent normal vertebrae.Results T2WI-SPAIR sequence showed that the vertebral morphology gradually worsened from the initial mild compression changes over time after vertebral fracture.Local bone collapse occurred at the upper edge of the verte-brae at>7-9 weeks,followed by stabilization.The initially diffuse and uniform high signal of the fractured vertebrae gradually changed a mixed signal,stabilizing around>9-12 weeks.Statistical analysis results revealed significant differences in ADC values between>1-2 weeks,>3-5 weeks,and>9-12 weeks post-fracture(P<0.05).Significant differences in FA values were also observed between≤1 week,>1-2 weeks,>3-5 weeks,>12 weeks,and>9-12 weeks post-fracture(P<0.05).Furthermore,ADC and FA values between the fractured and normal vertebrae also showed significant differences within the first 12 weeks post-fracture(P<0.05).Conclusion The T2WI-SPAIR sequence demonstrates specific patterns of morphological and signal changes dur-ing the recovery process of fractured vertebrae.Changes in DTI parameters,including ADC and FA values,in self-comparison within the fracture zone and comparison with normal regions,follow certain patterns.These findings can provide reliable imaging evidence for clinicians to make treatment decisions and estimate the time of vertebral injury.

Objective To explore the value of MR T2WI-spectral attenuated inversion recovery(T2WI-SPAIR)sequence and dif-fusion tensor imaging(DTI)in the recovery process of vertebral compression fractures over time.Methods Three patients aged 60-75 years with a clear time and mechanism of injury were selected.They underwent conventional MR sequences and DTI scans at eight time points.The morphological and signal changes of the fractured vertebrae on T2WI-SPAIR sequences were dynamically observed.Statistical analysis was performed on the apparent diffusion coefficient(ADC)and fractional anisotropy(FA)of the fractured verte-brae and adjacent normal vertebrae.Results T2WI-SPAIR sequence showed that the vertebral morphology gradually worsened from the initial mild compression changes over time after vertebral fracture.Local bone collapse occurred at the upper edge of the verte-brae at>7-9 weeks,followed by stabilization.The initially diffuse and uniform high signal of the fractured vertebrae gradually changed a mixed signal,stabilizing around>9-12 weeks.Statistical analysis results revealed significant differences in ADC values between>1-2 weeks,>3-5 weeks,and>9-12 weeks post-fracture(P<0.05).Significant differences in FA values were also observed between≤1 week,>1-2 weeks,>3-5 weeks,>12 weeks,and>9-12 weeks post-fracture(P<0.05).Furthermore,ADC and FA values between the fractured and normal vertebrae also showed significant differences within the first 12 weeks post-fracture(P<0.05).Conclusion The T2WI-SPAIR sequence demonstrates specific patterns of morphological and signal changes dur-ing the recovery process of fractured vertebrae.Changes in DTI parameters,including ADC and FA values,in self-comparison within the fracture zone and comparison with normal regions,follow certain patterns.These findings can provide reliable imaging evidence for clinicians to make treatment decisions and estimate the time of vertebral injury.

Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Objective To investigate the clinical features , diagnosis and key technique points of laparoscopic partial adrenalectomy for small adrenal pheochromocytoma . Methods From Oct.2006 to Jun. 2011, clinical data of 32 cases with small adrenal pheochromocytoma (≤3.0 cm) were collected and retro-spectively analyzed .Hypertension was observed in 12 patients, whereas 20 patients presented with adrenal incidentaloma .Thirteen patients had a left adrenal neoplasm , eighteen patients had a right adrenal tumor , while one patients had bilateral tumors .The positive rate of plasma-free metanephrines ( MNs) and 24-hours urinary catecholamine (CA) in diagnosing small renal pheochromocytomas was 92.6%(25/27) and 81.3%(26/32) respectively.The main localization diagnosis included ultrasonography , 131I-MIBG, and CT or MRI, with positive rates of 71.9%(23/32), 93.8%(15/16) and 96.9%(31/32) respectively.All the laparoscopic adrenalectomies were performed retroperitoneally .During the surgery , the internal part of the adrenal gland closing to the retroperitoneum was dissected first , and the whole adrenal gland was resected completely. Results Partial adrenalectomy was performed for 30 cases and radical adrenalectomy for 2 ca-ses.All operations were successful without perioperative or postoperative complications .The maximum diame-ter of tumor was 1.7±0.2 (1.0-3.0) cm.Histopathological results showed that all the cases were benign pheochromocytoma.The operative time was 82 (40-210) min.The estimated blood loss was 57 (20-180) ml.No patient required blood transfusion . Conclusions Plasma-free MNs, 24-hours urinary CA and VMA are important qualitative examinations in detection of adrenal pheochromocytoma .Ultrasonography , CT,MRI, and 131 I-MIBG are important in the localization of adrenal tumors .Retroperitoneal laparascopic partial adrenalectomy is the preferred choice in the management of small adrenal pheochromocytoma .Dissecting the internal part of the adrenal gland closing to the retroperitoneum first and exploring the whole adrenal tissue are the key technique points during the operations .