[Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma].

Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

[Type of CEBPA mutations in acute myeloid leukemia and their effect on prognosis].

Objective: To demonstrate the type of CEBPA gene mutations among patients with acute myeloid leukemia (AML), clinical characteristics, and prognostic effect on patient outcomes. Methods: Demographic data, clinical features, laboratory characteristics, and data about treatment and follow-up of 57 patients with CEBPA mutated AML diagnosed at Peking Union Medical College Hospital between April 2016 and November 2022 were collected and analyzed. Results: In total, 57 patients with CEBPA mutation accounted for 16.1% of all the 353 patients with AML, among which 28 patients had CEBPA-bZIPinf and 29 had CEBPA-other. Compared with the CEBPA-other group, the CEBPA-bZIPinf group was younger (54 vs 64 years, P=0.010), de novo AML was more common (P=0.001), and the level of bone marrow blast was higher (68.0% vs 36.3%, P=0.001). Moreover, 24 patients from the CEBPA-bZIPinf group and 19 from the CEBPA-other group received chemotherapy. The one-course complete remission (CR) rate of the CEBPA-bZIPinf group was significantly higher than that of the CEBPA-other (87.5% vs 47.4%, P=0.010) and CEBPA-wt (87.5% vs 50.3%, P=0.002) groups. After a median follow-up of 11 months, the median OS of the CEBPA-bZIPinf group was significantly longer than that of the CEBPA-wt group (not reached vs 22.1 months, P=0.012) . Conclusion: CEBPA-bZIPinf mutated AML is a unique clinical entity, with a younger age of diagnosis, better response to chemotherapy, and better prognosis.

[Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity].

Objective: To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion. Methods: Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma). Results: Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion. Conclusion: By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

[Efficacy of sutureless intrascleral intraocular lens fixation with the modified Yamane technique].

Objective: To evaluate the efficacy of sutureless intrascleral intraocular lens (IOL) fixation with the modified Yamane technique. Methods: It was a retrospective case series study. Patients undergoing sutureless intrascleral IOL fixation with the modified Yamane technique were included at Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University from January 2022 to September 2023. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), recorded as the logarithm of the minimum angle of resolution (logMAR), were measured before surgery and at 1 day, 3 days, 1 week, 1 month, and 3 months postoperatively. Refractive error and intraocular pressure were also checked. Anterior segment examination with a slit lamp microscope, fundus examination, anterior segment and posterior segment optical coherence tomography were performed. Intraoperative and postoperative ocular complications were documented. Results: A total of 53 patients (53 eyes) were included in this study, comprising 40 males and 13 females, with a median age of 60 (49, 68) years. Among them, the proportion of a history of trauma was 22.6% (12/53). There was 1 eye with intraoperative vitreous hemorrhage (1.9%). All eyes had no obvious hypotony, no obvious inflammation in the anterior chamber, and no pupillary abnormalities at 1 week after surgery. The mean follow-up time was (8.0±3.3) months (range, 3 to 16 months). There was no iris capture, re-dislocation, or haptic exposure of the IOL during the follow-up. The corneal endothelial cell density was (2 236±704) cells/mm2 preoperatively and (1 964±628) cells/mm2 at 1 month, with significant difference (P<0.001). The UCVA (logMAR) was 1.53±0.75 preoperatively, 0.18±0.17 at 1 month, 0.15±0.14 at 3 months, and 0.14±0.13 at the final visit (P<0.001). The UCVA (logMAR) at 1 month was significantly different from that at 3 months and the final visit (both P<0.05). At 1 month, 50.9% (27/53) of the eyes had an UCVA (logMAR)≤0.1, and the rate was 56.6% (30/53) at 3 months. The BCVA (logMAR) was 0.25±0.21, 0.03±0.06, 0.02±0.06, and 0.02±0.06 before surgery, at postoperative1 month, 3 months, and the final visit, respectively (P<0.001). The BCVA (logMAR) at 1 month was not significantly different from that at 3 months and the final visit (both P>0.05). The rate of the eyes with a BCVA (logMAR)≤0 was 81.1% (43/53) at 1 month and 83.0% (44/53) at 3 months. The IOL tilt was (5.18±2.60)° at postoperative 1 month and (5.08±2.48)° at postoperative 3 months, without statistically significant difference (P>0.05). The IOL decentration was (0.35±0.24) mm at postoperative 1 month and (0.32±0.24) mm at postoperative 3 months, without statistically significant difference (P>0.05). Conclusion: Sutureless intrascleral IOL fixation with the modified Yamane technique is simpler and more minimally invasive to achieve a stable and centered IOL implantation with fewer complications and good visual prognosis.

[Application of the Second Revision of the International Staging System (R2-ISS) in the prognostic assessment of newly diagnosed multiple myeloma].

Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed. Results: ①326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS Ⅱ patients. The median progression-free survival (PFS) time of R2-ISS Ⅰ, R2-ISS Ⅱ, R2-ISS Ⅲ, and R2-ISS Ⅳ was 52, 29, 20, and 15 months (P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months (P<0.001). Multifactor analysis revealed that ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. ②The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. ③The median PFS for 1q+-related double-hit in R2-ISS Ⅲ and Ⅳ were 20, 15 months (P=0.084) and the median OS were 35, 36 months (P=0.786), respectively. In R2-ISS Ⅲ, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months (P=0.974), while the median OS was 35, 47, and 56 months (P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping (P<0.001) . Conclusions: The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS Ⅱ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.

[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

[Precision nutritional therapy in gastrointestinal tumor].

Apart from individual genetic background, unhealthy lifestyle and diet, etc., nutrition also plays an important role in the occurrence and progression of gastrointestinal tumors. Although some patients with gastrointestinal tumors can be satisfied with the traditional nutritional support, it is apparently inadequate for the systemic management of all patients. Precision nutrition support, also known as personalized nutrition support, refers to safe and efficient individualized nutrition intervention based on the investigation of individual genetic background, life characteristics, metabolic indicators, intestinal microbial characteristics, and physiological status factors through big data analysis for the prevention and treatment of chronic diseases. This review focuses on the relationship between nutrition and gastrointestinal tumors and discusses the progress of precision nutrition support therapy in the gastrointestinal tumors. Based on this, we hope to achieve effective personalized intervention protocols, and improve the clinical outcome and the overall oncology care of gastrointestinal tumors.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Influencing factors of visual prognosis in patients with persistent submacular fluid after successful scleral buckle surgery for macula-off retinal detachment].

Objective: To investigate the factors influencing visual outcomes in patients with rhegmatogenous retinal detachment (RRD) who developed persistent submacular fluid (PSF) after scleral buckling surgery. Methods: A retrospective case series analysis was conducted. Clinical data were collected from patients who underwent successful scleral buckling surgery for RRD at Beijing Tongren Hospital from June 2020 to December 2022 and were followed up. Patients with RRD involving the macular area preoperatively and graded as C1 or below in proliferative vitreoretinopathy (PVR) were included. Surgical procedures followed a minimally invasive scleral buckling approach. PSF was defined as subretinal fluid persisting for more than 1 month postoperatively. Regular follow-up visits were scheduled at postoperative days 1, 3, 7, 2 weeks, and 1 month, followed by monthly visits until complete PSF absorption. Best-corrected visual acuity (BCVA), intraocular pressure, refractive error, slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and optical coherence tomography (OCT) were performed at each follow-up time point. Eyes were divided into two groups based on whether the final follow-up BCVA was≥0.5 and whether the absorption time of PSF was>6 months, and statistical analysis was performed using the Wilcoxon signed-rank test, chi-squared test, and Mann-Whitney U test. Results: A total of 46 patients (46 eyes) were included in this study, comprising 25 males and 21 females, with a median age of 32.5 (21.0, 57.3) years. The preoperative equivalent spherical refractive error was (-5.27±4.05) D, and the preoperative duration of illness was 30 (14, 92) days. The preoperative BCVA (logarithm of the minimum angle of resolution,logMAR) was 2.00 (1.00, 2.50). Scleral buckle surgery was performed in 28 eyes (60.9%), and 18 eyes (39.1%) underwent scleral buckle surgery combined with encircling. External drainage was performed in 15 eyes (32.6%), while 31 eyes (67.4%) had no external drainage. BCVA (logMAR) at 1 month, 3 months, and the final follow-up postoperatively was 0.60 (0.50, 1.00), 0.40 (0.28, 0.53), and 0.15 (0.00, 0.50), respectively. In the final follow-up, 31 eyes (67.4%) achieved BCVA≥0.5, and 26 eyes (56.5%) had continuous ellipsoid zone on OCT. The differences in BCVA (logMAR) between preoperative, 1 month, 3 months, and the final follow-up were statistically significant (Z=-5.85, -5.63, -4.73;all P<0.001). The absorption time of PSF postoperatively was 6.50 (3.00, 9.00) months, ranging from 2 to 19 months. The eyes with PSF duration<3 months, 3-6 months, and>6 months were 12 eyes (26.1%), 11 eyes (23.9%), and 23 eyes (50.0%), respectively. There were statistically significant differences between the two groups in preoperative BCVA≥0.05, preoperative duration of illness within 1 month, PVR grading, surgical method, and continuous ellipsoid zone on OCT (all P<0.05), while there were no statistically significant differences between the two groups in PSF absorption time, different types of PSF, and intraoperative drainage (all P>0.05). The PSF absorption time in the two groups was 7 (3, 10) months and 6 (4, 8) months, with no statistically significant difference (P>0.05). Conclusions: Preoperative visual acuity, duration of illness, and PVR grading are factors influencing visual outcomes in patients with RRD who have undergone scleral buckling surgery and develop PSF. In contrast, intraoperative drainage, PSF absorption time, and different PSF types are not factors affecting visual prognosis. Although PSF may persist for a long time after scleral buckling surgery, it does not significantly impact long-term visual outcomes.

[Effects of modified proper digital artery island flap in repairing complex fingertip defects].

Objective: To investigate the surgical method and clinical effects of the modified proper digital artery island flap in repairing complex fingertip defects. Methods: A retrospective observational study was conducted. From January 2017 to December 2021, 15 patients (15 fingers) with complex fingertip defects, involving the pulp, nail bed, and lateral wall of the nail, who met the inclusion criteria were admitted into General Hospital of Northern Theater Command, including 11 males and 4 females, aged from 18 to 55 years. The area of the post debridement wound was from 2.5 cm×2.0 cm to 3.5 cm×3.5 cm, and all the wounds were repaired by using modified proper digital artery island flap (including 3 parts: main flap, tongue-shaped flap, and triangular flap), of which the main flap was used to cover the finger pulp defect, the tongue-shaped flap was used to cover the nail bed and the nail lateral wall defect, and the triangular flap was inserted into the edge of the finger pulp wound to cover the vessel pedicle. The range of the flap ranged from 3.0 cm×2.0 cm to 4.5 cm×3.0 cm. The wound at the donor site was repaired with full-thickness skin graft of the groin, and the donor site of the skin graft was sutured directly. After operation, the survival of the flap and skin graft as well as and the appearance of the affected finger were observed. During the follow-up, the fingertip morphology of the affected finger was observed, two-point discrimination distance of the affected finger pulp was measured, and the patients' satisfaction with the efficacy (including very satisfied, satisfied, and dissatisfied) was asked, and the affected finger function was evaluated by the total active movement (TAM) system evaluation standard recommended by American Academy for Surgery of Hand. Results: After operation, the main flaps and skin grafts in 15 patients all survived; but the incision at the edge of tongue-shaped flap in one patient healed poorly, and one patient developed venous stasis at the distal end of the tongue-shaped flap; the triangular flap at the pedicle was slightly bloated in the early postoperative period and became smooth after 2 to 3 months. Overall, two patients developed subcutaneous hematoma in their flaps. All the complications were healed by appropriate dressing change, suture removal, or compression bandaging. After operation, the appearance of the flap was full and formed a prominent fingertip shape. During the follow-up of 6 months to 5 years, the fingertips of the affected fingers were prominent and full; the two-point discrimination distance of the affected finger pulp was (8.6±1.4) mm; 8 patients were very satisfied with the efficacy, 6 patients were satisfied, and one patient was dissatisfied; the functional assessment of the affected fingers were all excellent. Conclusions: The modified proper digital artery island flap can repair complex fingertip defects involving the pulp, nail bed, and lateral wall of the nail. The operation is simple, and the shape and function of the fingertip are good after surgery.

[Management strategy of femoral artery pseudoaneurysm combined with infectious wounds].

Objective: To investigate the surgical treatment methods of femoral artery pseudoaneurysm combined with infectious wounds and to evaluate the clinical effects. Methods: The retrospective observational research method was used. Twelve patients with femoral artery pseudoaneurysm combined with infectious wounds who met the inclusion criteria were admitted to Nanjing University of Chinese Medicine Wuxi Integrated Traditional Chinese and Western Medicine Hospital (Affiliated Hospital of Jiangnan University) from October 2014 to September 2022, including 6 males and 6 females, aged from 46 to 78 years. In the primary operation, debridement, tumor resection, and artery suture/venous grafting to repair the artery/artery ligation were performed, and the wound area after tumor resection ranged from 4.0 cm×1.5 cm to 12.0 cm×6.5 cm. Wounds that could be sutured were treated with tension reduction suture and extracutaneous continuous vacuum sealing drainage (VSD), while large wounds that could not be sutured were treated with VSD to control infection. In the secondary operation, tension reduction suture was performed to repair the wounds that could be sutured; large wounds were repaired with adjacent translocated flaps with area of 9.0 cm×5.0 cm to 15.0 cm×7.0 cm. Additionally, when the length of the exposed femoral artery was equal to or over 3.0 cm, the wounds were repaired with additional rectus femoris muscle flap with length of 15.0 to 18.0 cm. The donor areas of the flaps were directly sutured. The wound with artery ligation was treated with stamp skin grafting and continuous VSD. The bacterial culture results of the wound exudate samples on admission were recorded. The intraoperative blood loss, the location of femoral artery rupture, the artery treatment method, and the wound repair method in the primary operation were recorded, and the durations of catheter lavage, catheter drainage, and VSD treatment, and the drainage volume after the operation were recorded. The repair method of wounds in the secondary operation, the durations of catheter drainage and VSD treatment, and the total drainage volume after the operation were recorded. The survivals of flap/muscle flap/stamp skin grafts were observed, and the wound healing time was recorded. Follow-up after discharge was performed to evaluate the quality of wound healing and the walking function and to check whether the pulsatile mass disappeared. B-ultrasound or computed tomography angiography (CTA) was performed again to observe potential pseudoaneurysm recurrence and evaluate the patency of blood flow of the femoral artery. Results: The bacterial culture results of wound exudate samples of all the patients were positive on admission. The blood loss was 150 to 750 mL in the primary operation. The arterial ruptures were located in the femoral artery in 8 cases, in the external iliac artery in 2 cases, and in the femoral arteriovenous fistula in 2 cases. Six cases received direct artery suture, 4 cases received autologous great saphenous vein grafting to repair the artery, 1 case received autologous great saphenous vein bypass surgery, and 1 case received artery ligation. The primary wound suture was performed in 4 cases, along with catheter lavage for 3 to 5 days, catheter drainage for 4 to 6 days, VSD treatment for 5 to 7 days, and a total drainage volume of 80 to 450 mL after the surgery. In the secondary operation, the wounds were sutured directly in 3 cases along with catheter drainage for 2 to 3 days, the wound was repaired with scalp stamp skin graft and VSD treatment for 5 days in 1 case, the wounds were repaired with adjacent translocated flaps in 2 cases with catheter drainage for 2 to 3 days, and the wounds were repaired with rectus femoris muscle flaps+adjacent translocated flaps in 2 cases with catheter drainage for 3 to 5 days . The total drainage volume after the secondary operation ranged from 150 to 400 mL. All the skin flaps/muscle flaps/skin grafts survived after operation. The wound healing time ranged from 15 to 36 days after the primary operation. Follow-up of 2 to 8 months after discharge showed that the wounds of all patients healed well. One patient who underwent femoral artery ligation had calf amputation due to foot ischemic necrosis, and the rest of the patients regained normal walking ability. The pulsatile mass disappeared in inguinal region of all patients. B-ultrasound or CTA re-examination in 6 patients showed that the blood flow of femoral artery had good patency, and there was no pseudoaneurysm recurrence. Conclusions: Early debridement, tumor resection, and individualized artery treatment should be performed in patients with femoral artery pseudoaneurysm combined with infected wounds. Besides, proper drainage and personalized repair strategy should be conducted according to the wound condition to achieve a good outcome.

[Evaluation of spinopelvic alignment according to Roussouly classification can predict the occurrence of adjacent segment disease after lumbar fusion].

Objective: To investigate the correlation of spinopelvic alignment according to Roussouly classification on the occurrence of adjacent segment disease (ASD) in the patients undergoing fusion surgery for lumbar degenerative diseases. Methods: A cross-sectional study. Clinical data of 166 consecutive patients who had undergone lumbar fusion between January 2009 and January 2019 in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University and Affiliated Drum Tower Hospital of Medical School of Nanjing University were retrospectively reviewed. There were 59 males and 107 females, with an average age of (58.6±9.5) years (ranged 41-78 years). Fusion length averagely spanned (1.7±0.7) levels (ranged 1-3 levels). The patients were classified by both "theoretical" (based on pelvic incidence (PI)) and "current"(based on sacral slope (SS)) Roussouly types. The patients were classified as "matched" if their "current" shape matched the "theoretical" type and otherwise as "unmatched". Multivariate logistic regression analysis of the variables recruited from univariate analyses was performed to identify the factors independently associated with the development of ASD after lumbar fusion. Results: The average follow-up duration after initial surgery was (49.2±20.7) months (ranged 25 to 134 months). Thirty (18.1%, 30/166) patients were diagnosed as ASD. Postoperatively, two thirds of the patients who suffered ASD after surgery were unmatched, while 36.8% (50/136) of the patients without ASD had unmatched type. Univariate analyses showed that older age, more fusion levels, float fusion, pre-and postoperative worse spinopelvic alignment, and postoperative unmatched Roussouly type were identified as risk factors of ASD. Multivariate logistic regression analysis identified postoperative Roussouly type mismatch (OR=3.310, 95%CI: 1.282-8.545, P=0.013), old age (OR=1.074, 95%CI: 1.019-1.131, P=0.008) and postoperative SS (OR=0.928, 95%CI: 0.865-0.995, P=0.036) as the independent risk factors of development of ASD after lumbar fusion. Conclusion: A significant association between postoperative sagittal malalignment and occurrence of ASD is detected, the evaluation of sagittal alignment by Roussouly classification could help predict the occurrence of ASD.

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer.

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.

[Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant].

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

[Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance].

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.