Objective:To investigate the strategy of using tissue flaps for repairing scalp defects with exposed skull wounds.Methods:This study was a retrospective observational study. From January 2019 to December 2023, 18 patients (13 males and 5 females, aged 17-59 years) with different scalp defect combined with skull exposure area (hereafter referred to as scalp defect area) who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University. After debridement, the scalp defect area was 1 cm×1 cm to 25 cm×25 cm. For patients with scalp defect area < 9 cm 2 and good local conditions of the surrounding scalp, local flaps with area of 2 cm×2 cm-5 cm×5 cm were used for wound repair. The wound in the donor site of the flap was pulled together and sutured. If the suture tension was large, the skin graft from the head was taken and transplanted for wound repair. For patients with scalp defect area > 9 cm 2 and ≤1/4 of the total scalp area, expanded flaps with area of 5 cm×3 cm-12 cm×12 cm were used for wound repair. The wound in the donor site of the flap was pulled together and sutured directly. For patients with scalp defect area >1/4 and ≤1/2 of the total scalp area, free transplantation of anterolateral thigh flaps with area of 9 cm×7 cm-29 cm×14 cm were used for wound repair. The wound in the donor site of the flap was sutured in layers, and the skin graft from the ipsilateral thigh was transplanted for repair if the tension was large. For patients with scalp defect area >1/2 of the total scalp area, free greater omental flap (28 cm×23 cm-29 cm×26 cm in area) transplantation and thigh skin graft were used for wound repair. The abdominal incision caused by cutting the greater omental flap was sutured directly. The types of tissue flaps were recorded during operation. After operation, the survival of tissue flaps and skin graft in the recipient sites was observed, and the wound healing of flap donor sites/abdominal incision caused by cutting the greater omental flap was observed. During follow up, the survival of tissue flaps and the scar hyperplasia of flap donor site/abdominal incision caused by cutting the greater omental flap were observed. At the last follow-up, the skull necrosis was evaluated by computed tomography scan. Results:For the scalp defect with exposed skull wounds in this group of cases, 4 cases were repaired with local flaps, of which 2 cases were repaired with V-Y advancement flaps, and 2 cases were repaired with local double-pedicle vault stone flaps. The flaps survived completely after operation. Five cases were repaired with expanded flaps, of which 1 patient was implanted with 2 skin and soft tissue expanders, and 4 patients were implanted with 1 skin and soft tissue expander. The expanded flaps survived completely after operation. Seven cases were repaired with free transplantation of anterolateral thigh flaps. After operation, the flap in 6 cases survived, and the distal end of the flap was necrotic in 1 case, and the wound healed well after debridement and suture. Two cases were repaired with free transplantation of greater omental flaps and thigh skin graft, and the greater omental flap and skin graft in the recipient site survived well after operation. After operation, the wound of flap donor site/abdominal incision caused by cutting the greater omental flap healed well. During follow-up, all tissue flaps survived well without skull exposure; the scar hyperplasia of flap donor site/abdominal incision caused by cutting the greater omental flap was not obvious. At the last follow-up, computed tomography scan showed that all patients had no skull necrosis.Conclusions:According to the size of scalp defect, local flap, expanded flap, free anterolateral thigh flap, and free greater omental flap+skin graft are selected successively from small to large to repair the wounds, and the effect is good, which is worthy of clinical promotion.

Objective:To explore the clinical characteristics,treatments,and pregnancy outcomes of pregnant women with malignant ovari-an tumors.Methods:We retrospectively analyzed the clinical data of 11 patients with pregnancies complicated by malignant ovarian tu-mors,including the pathological types,clinical staging,surgical methods,pregnancy outcomes,and follow-up results from January 2012 to December 2022.Results:Among the eleven patients followed up until October 2023,six had primary ovarian tumors and five had metastat-ic ovarian tumors.Among the six primary ovarian tumors,five were epithelial tumors(one in stage ⅠA,two in stage ⅠC,one in stage ⅢA,one in stage ⅡB)and one was a malignant germ cell tumor(stage ⅠA).Four patients were diagnosed at stage Ⅰ:one in early pregnancy who continued the pregnancy and underwent tumor surgery post-delivery,and three in late pregnancy who under went tumor surgery dur-ing cesarean section or postpartum.Two patients were diagnosed at stage Ⅲ:one in early pregnancy with surgery after the termination of pregnancy,and one in late pregnancy with surgery during a cesarean section.Five patients had successful births,including two premature and three full-term births,all alive and healthy.The six patients with primary ovarian tumors were followed up for 18-133 months,and all survived.Five patients had ovarian metastatic tumors,including four cases of Krukenberg tumors and one of a cervical tumor.Two patients were diagnosed in the first trimester and underwent tumor reduction post-abortion.One patient was diagnosed in the second trimester,had to continue the pregnancy,and underwent tumor reduction post-delivery.Two patients were diagnosed in the third trimester:one under-went cesarean section and ovarian tumor resection simultaneously,and the other underwent tumor resection post-delivery.Three patients had successful births,all premature but alive.One of the five patients with ovarian metastatic tumors was lost to follow-up;the remaining four were followed up for 3-22 months,and all deceased.Conclusions:The prognosis for patients with pregnancies complicated by ovarian primary tumors is favorable,whereas the prognosis for patients with pregnancies complicated by ovarian metastatic tumors is poor,neces-sitating greater clinical attention.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

Objective:To explore the application value of case-based learning (CBL) and problem-based learning (PBL) dual-track teaching mode in the standardized resident training in laboratory medicine.Methods:The students of Grade 2017 and Grade 2018, who underwent standardized resident training of laboratory medicine in the Second Affiliated Hospital of Wenzhou Medical University from September 2017 to June 2021, were selected in this study. Seven students of Grade 2017 were served as the traditional lecture teaching group (traditional teaching group), and 12 students of Grade 2018 were assigned to the CBL-PBL dual-track teaching mode group (CBL-PBL group). Students of the two groups received 22 months of laboratory specialty training, and underwent one admission theory assessment,two mid-term theory assessments, annual professional level test, final theory assessment, final practical skills assessment as well as questionnaire survey. The questionnaire was distributed and finished anonymously after the final assessment. Survey indicators included ability assessment on solving clinical problem, assessment on the theoretical knowledge, computer operation skill, preparation time before teaching, teaching method satisfaction degree and clinical recognition. The results were divided into 5 categories: extremely agree, agree, general, disagree and extremely disagree, respectively (ranked as 5, 4, 3, 2, and 1). The Cronbach′s α coefficient was used to analyze the reliability of the questionnaire.Results:The mid-term theory assessment, annual professional level test and assessment results of clinical outcome interpretation were significantly higher in CBL-PBL dual-track teaching mode group than those in traditional lecture teaching group (all P<0.05). The performance after standardized resident training was significantly higher in the CBL-PBL group than in the traditional teaching group ( P<0.05). The Cronbach′s α coefficient of questionnaire reliability analysis was 0.938. Parameters assessment results including improved clinical problem-solving skills, computer operation skill, the ability to analyze and solve problems, the ability of innovation and adaptation, the learning interest, the ability of autonomous learning, teaching method satisfaction and conventional application to clinical recognition scores were all significantly better in the CBL-PBL group than those in the traditional teaching group (all P<0.05). Conclusion:The application of CBL-PBL dual-track teaching mode for the standardized resident training in laboratory medicine can effectively improve the assessment results and performance of students undergoing standardized resident training, and help to cultivate high quality medical laboratory professionals.

OBJECTIVE To establish a quantitative analysis method for the quality control components in Tenghuang jiangu capsules， and predict the possible action mechanism of the quality control components. METHODS Seven key quality control components in Tenghuang jiangu capsules were quantitatively analyzed by UHPLC-Q-Orbitrap HRMS. The “component-target” network was constructed based on network pharmacology， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and gene ontology （GO） function enrichment analysis were further conducted to find the key signaling pathways. RESULTS The average contents of succinic acid， hyperoside， gallic acid， kaempferol， naringin， naringenin and protocatechuic acid in 20 batches of Tenghuang jiangu capsules were 520.92， 67.67， 129.48， 4.74， 397.45， 5.66 and 376.62 μg/g， respectively. The results of network pharmacology showed that the 62 key target genes of the quality control components of the drug included AKT1， TNF， VEGFA， MMP9， PTGS2， etc. They were mainly enriched in cytokine receptor interaction， nuclear factor， tumor necrosis factor， interleukin 17， rheumatoid arthritis， Toll-like receptor and other signal pathways， involving inflammatory reaction， signal transduction， protein phosphorylation and other biological processes， kytoplasm， cell membrane and other cell components， as well as enzyme activity， energy activity and other molecular functions. CONCLUSIONS The established UHPLC- Q-Orbitrap HRMS method can be used for the quantitative analysis of the quality control components of Tenghuang jiangu capsule. Its quality control components may be mapped to inflammatory pathways related to bone diseases such as rheumatoid arthritis and Toll-like receptors through AKT1， TNF， VEGFA and other key targets， so as to play a therapeutic role.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Mycobacterium tuberculosis is the causative agent of tuberculosis(TB),which is still the leading cause of mortality from a single infectious disease worldwide.The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M.tuberculosis.Here,we harnessed an endogenous type Ⅲ-A CRISPR/Cas10 system of M.tuberculosis for efficient gene editing and RNA interference(RNAi).This simple and easy method only needs to transform a single mini-CRISPR array plasmid,thus avoiding the introduction of exogenous protein and minimizing proteotoxicity.We demonstrated that M.tuberculosis genes can be efficiently and specifically knocked in/out by this system as con-firmed by DNA high-throughput sequencing.This system was further applied to single-and multiple-gene RNAi.Moreover,we successfully performed genome-wide RNAi screening to identify M.tuberculosis genes regulating in vitro and intracellular growth.This system can be extensively used for exploring the functional genomics of M.tuberculosis and facilitate the development of novel anti-TB drugs and vaccines.

Objective:To explore the clinical value of cryoablation technology in the treatment of patients with primary tumor recurrence after radical radiotherapy for prostate cancer.Methods:The clinical data of 21 patients with prostate cancer recurrence after radical radiotherapy in the Fudan University Affiliated Cancer Hospital from August 2017 to February 2021 was retrospectively analyzed. The average age was 73.1 (57.3-85.0) years old, and the Gleason score was 6 in 5 cases, 7 in 8 cases, and ≥8 in 8 cases. The clinical stage of the first diagnosis: 13 cases of cT 2 stage; 8 cases of cT 3 stage. The baseline PSA before radiotherapy was 35.3 (6.4-78.5) ng/ml, and the lowest PSA after radiotherapy was 1.8 ng/ml. After a median follow-up of 8 (3-12) months, all patients were detected with persistently elevated PSA. Pelvic MRI and PSMA SPECT showed that the primary prostate lesion had recurred. PSA before cryoablation was 4.1 (1.8-14.4) ng/ml. Comprehensive assessment of preoperative examination showed that the patient only had a recurrence of the primary tumor, and no lymph node or distant metastasis was seen. An argon-helium cryogenic surgical treatment system was used to place 1 to 3 cryo-needles for recurring lesions, and cryoablation was performed using two cold and hot cycles. Observation indicators include prognostic indicators such as PSA, recurrence and metastasis, and the occurrence of adverse reactions. Results:Complications after cryoablation include: 2 cases of urinary retention, 1 case of urinary tract infection, and 2 cases of urination with tissue shedding. The PSA of 11 cases decreased rapidly 2 to 3 months after operation, and dropped to the lowest median value of 0.4 (0.003 to 2.8) ng/ml. After cryoablation, the median follow-up was 18 (6-51) months. Imaging examinations in 1 case showed that the prostate still had limited diffusion or increased PSMA uptake, and 4 cases had PSA progression but no recurrence or metastasis. The median recurrence time for advanced patients was 13 (4-36) months. Larger prostate volume ( P<0.001) and higher blood PSA before ablation( P=0.021) were related to biochemical recurrence. Conclusions:Prostate cryoablation could delay the progression of the primary tumor after radical radiotherapy for prostate cancer. The incidence of complications such as urinary retention and urinary tract infection is not high, and it is generally safe and controllable.