CIC-rearranged sarcoma: a clinicopathological analysis of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

One new glycoside naphthopyranone from the Yiling cave-derived Metarhizium anisopliae NHC-M3-2 / 药学学报

Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC50 and CC50 of compound 3 against HBV were 4.5 μmol·L-1 and 92.3 μmol·L-1, respectively. This is the first report of the antiviral activity of compound 3.

Pedicled omentum packing of the pelvic floor in the prevention of short-term postoperative complications after laparoscopic Miles precedure / 中华普通外科杂志

Objective:To evaluate the effect of pedicled omentum packing of pelvic floor after laparoscopic Miles precedure in the prevention of short-term postoperative complications.Methods:Seventy-two patients undergoing laparoscopic combined abdominal perineal resection for rectal cancer at He'nan Tumor Hospital from Jan 2014 to Aug 2021 were retrospectively reviewed. The observation group underwent pelvic floor reconstruction with pedicled omentum, while in control group the pelvic floor was leaving unconstructed.Results:There was no intestinal obstruction in the observation group. There were 5 cases of intestinal obstruction in the control group. Three were recovered by conservative treatment, 2 cases underwent laparotomy and 1 case underwent anastomosis between small intestine and small intestine. The incidence of intestinal obstruction between 2 groups was statistically different (0 vs. 14%, χ2=5.083, P=0.024 ). The operation time, hospital stay between the two groups were statistically different [(195±13) min vs. (159±9) min, t=10.047, P=0.000; (11.9±0.9) d vs. (14.9±2.1) d, t=-5.996, P=0.000 ). Between the two groups, there were no significant differences in the incidence of presacral infection , pulmonary infection, venous thrombosis and intraoperative blood loss (all P>0.05) . Conclusion:Pedicled greater omentum used in pelvic floor reconstruction after laparoscopic Miles procedure reduces the incidence of short-term postoperative complications, especially of intestinal obstruction.

Risk factors and functional evaluation of recurrence after resection of thigh soft tissue malignant tumor / 中华骨科杂志

Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.

Diagnostic analysis of cTTE for patent foramen ovale and the value of combined NLR monitoring in predicting cryptogenic stroke / 中国医师杂志

Objective:To investigate the diagnostic value of transthoracic echocardiographic contrast-enhanced ultrasound (cTTE) in patent foramen ovale (PFO) and the value of combined neutrophil to lymphocyte ratio (NLR) in predicting cryptogenic stroke.Methods:A total of 120 suspected PFO patients admitted to the Affiliated Hospital of Jining Medical College from January 2021 to December 2021 were selected and examined by cTTE and transesophageal echocardiography (TEE) to analyze the diagnostic value of cTTE in PFO. The clinical data and cTTE parameters of PFO patients with and without cryptogenic stroke were analyzed.Results:A total of 69 patients with PFO were confirmed. Among the 69 patients, 23 patients with cryptogenic stroke and 46 patients without cryptogenic stroke were confirmed by magnetic resonance imaging (MRI). The value of cTTE in the diagnosis of PFO was high: the sensitivity, accuracy and negative predictive value of cTTE under Valsalva motion in the diagnosis of PFO were 95.65%, 91.67% and 93.62%, respectively, which were significantly higher than that of cTTE at rest (all P<0.05). The NLR, the proportion of large shunt of PFO right to left shunt (PFO-RLS), the inlet width of patent foramen ovale (PFO) and the outlet width of PFO in patients with PFO complicated with cryptogenic stroke were (3.01±0.89), 43.48%(10/23), (2.54±0.65)mm and (1.51±0.35)mm, respectively, which were significantly higher than those in patients without cryptogenic stroke (all P<0.05). Logistic regression analysis showed that NLR and the degree of PFO-RLS shunt were the influencing factors of patients with PFO complicated with cryptogenic stroke (both P<0.05). The area under the Receiver operating characteristic (ROC) curve predicted by NLR combined with PFO-RLS shunt was 0.905, which was significantly higher than that predicted by NLR and PFO-RLS shunt alone (all P<0.05). Conclusions:cTTE has a good value in the diagnosis of PFO, and cTTE combined with NLR has a certain application value in predicting PFO complicated with cryptogenic stroke.

Application value of transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position / 中华消化外科杂志

Objective:To investigate the application value of transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position.Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 114 patients who underwent com-plete resection of presacral cyst in Henan Cancer Hospital from August 2012 to October 2021 were collected. There were 14 males and 100 females, aged (35±9)years. All patients were diagnosed as presacral cysts by preoperative magnetic resonance imaging. Of the 114 patients, 76 patients undergoing intraoperative perineal arc incision approach in the lithotomy position were divided into the innovative group, and 38 patients undergoing intraoperative Kraske approach were divided into the traditional group. Observation indicators: (1) surgical situations and specimen; (2) postoperative situations; (3) Follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical situations and specimen. The operation time, volume of intraoperative blood loss, cases with intraoperative combined transabdominal approach or sacrectomy were (137±20)minutes, (261±101)mL, 0 in the innovation group, versus (136±34)minutes, (261±116)mL, 15 in the tradi-tional group, showing no significant difference in the operation time and volume of intraoperative blood loss between the two groups ( t=0.18, 0, P>0.05) and showing a significant difference in cases with intraoperative combined transabdominal approach or sacrectomy between the two groups ( P<0.05). Results of postoperative specimen anatomy in patients of the two groups showed complete removal of the cyst. (2) Postoperative situations. The time to postoperative removing presacral drainage tube, duration of postoperative hospital stay, cases with postoperative second stage healing of incision were (11.4±2.1)days, (13.5±3.5)days, 23 in the innovation group, versus (11.5±1.9)days, (13.7±3.8)days, 4 in the traditional group, showing no significant difference in the time to post-operative removing presacral drainage tube and duration of postoperative hospital stay between the two groups ( t=-0.20, -0.24, P>0.05) and showing a significant difference in cases with postoperative second stage healing of incision between the two groups ( χ2=5.46, P<0.05). Cases with postoperative severe complications were 4 and 2 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). (3) Follow-up. All 114 patients were followed up for 48(range, 6?108)months. Cases with recurrence of cysts were 2 and 0 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). During the follow-up period, the anal defecation control function of all patients was classified as grade A?B of Williams score. Conclusions:The transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position is safe and feasible. Compared with Kraske approach, the transverse perineal arc incision approach in the lithotomy position is more suitable for patients with high presacral cyst.

Effects of ursolic acid on iron death in endometrial stromal cells via JAK2/STAT3 signaling pathway / 中华内分泌外科杂志

Objective:To investigate the effects of ursolic acid (UA) on proliferation, migration and iron death of ectopic endometrial stromal cells (EESCs) and its mechanism.Methods:Mouse model of endometriosis was established and the primary EESCs were isolated. The cells were treated with UA at different concentrations (0, 2.5, 5, 10, 20, 40, 50, 80, 100, 200 μmol/L). The cells were divided into Control group (normal culture), 2.5 μmol/L UA group (2.5 μmol/L UA treatment), 5.0 μmol/L UA group (5.0 μmol/L UA treatment), 10.0 μmol/L UA group (10 μmol/L UA treatment), and UA+DUSP19 group (10 μmol/L UA+50 μmol/L JAK2/STAT3 signal pathway activator DUSP19 treatment). Cell survival rate was detected by CCK-8 method. Cell proliferation was detected by plate cloning method. Transwell chamber assay was used to detect cell migration. The levels of Fe 2+ and the contents of malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD) were detected by kit. Protein expression levels of Ki67, PCNA, CyclinD1, p-JAK2, p-STAT3, JAK2 and STAT3 were detected by western blot. Results:The number of clones in Control, 2.5 μmol/L UA, 5.0 μmol/L UA and 10.0 μmol/L UA groups were as follows: 152.22±15.47, 121.22±11.54, 92.00±5.54, 66.44±6.88; Ki67 protein expression was 1.08±0.10, 0.73±0.07, 0.61±0.06, 0.45±0.02, respectively; The expression of PCNA protein was 0.85±0.07, 0.64±0.05, 0.41±0.03, 0.31±0.05, respectively; CyclinD1 protein expression levels were 0.98±0.11, 0.65±0.06, 0.51±0.05, 0.42±0.07, respectively. The migration numbers were 92.78±6.27, 62.22±2.20, 50.22±4.59 and 39.11±4.33, respectively; Fe 2+ levels were (1.06±0.07) μmol/g, (1.21±0.11) μmol/g, (1.33±0.08) μmol/g, (1.47±0.09) μmol/g, respectively; MDA content was (0.48±0.06) μmol/g, (0.65±0.07) μmol/g, (0.85±0.08) μmol/g, (1.03±0.11) μmol/g, respectively; ROS contents were (19.85±1.21) %, (24.83±2.79) %, (29.04±1.86) %, (33.87±2.45) %, respectively; SOD content were (36.41±3.56) U/mg, (31.03±2.81) U/mg, (25.63±2.84) U/mg, (19.62±1.67) U/mg, respectively; p-JAK2 protein expression was 0.85±0.10, 0.75±0.06, 0.53±0.05, 0.31±0.03, respectively; p-STAT3 protein expression was 1.08±0.11, 0.79±0.06, 0.63±0.07, 0.42±0.03, respectively. The p-JAK2 protein content in UA group and UA+DUSP19 group was 0.38±0.05 and 0.75±0.08, respectively; p-STAT3 protein expression was 0.46±0.04 and 0.80±0.03, respectively; The cell survival rates were (52.55±2.44) % and (82.18±4.72) %, respectively; Fe 2+ levels were (1.57±0.06) μmol/g and (1.21±0.13) μmol/g, respectively. The differences in the above indicators between the Control group and the 2.5 μmol/L UA group, 5.0 μmol/L UA group and 10.0 μmol/L UA group were statistically significant ( P<0.05). There were statistically significant differences among 2.5 μmol/L UA group, 5.0 μmol/L UA group and 10.0 μmol/L UA group ( P<0.05). There were statistically significant differences in p-JAK2, p-STAT3, cell survival rate and Fe 2+ levels between UA group and UA+DUSP19 group ( P<0.05) . Conclusion:Ursolic acid can inhibit the proliferation and migration of EESCs cells and induce iron death by regulating JAK2/STAT3 signaling pathway, thus playing a protective role in endometriosis.

Effect of single nucleotide variation of OPG gene on osteoporosis in patients with gestational diabetes mellitus / 中华内分泌外科杂志

Objective:To investigate the effect of single nucleotide variation of osteoprotegerin (OPG) gene on the occurrence of osteoporosis (OP) in patients with gestational diabetes mellitus (GDM) .Methods:From Apr. 2018 to Apr. 2022, 276 pregnant women with GDM who underwent prenatal examination and gave birth in Linyi People’s Hospital were collected for analysis, general data were collected and bone mineral density was tested. According to the bone mineral density test results, they were divided into normal group and OP group. The OPG genotype was tested, and the general information, OPG genotype and allele frequency of the two groups were compared. The differences in bone mineral density among different genotypes of OPG were compared, and the genotypes affecting the risk of OP in GDM patients were analyzed.Results:There was no significant difference in the general data of the two groups of patients (all P>0.05). The allelic distribution of the rs3134069 and rs2073618 loci of the OPG gene in the two groups of patients conformed to the Hardy-Weinberg equilibrium law (all P>0.05). There was a statistically significant difference in the frequency of the AC genotype at rs3134069 between the two groups ( χ2=7.75, P=0.005). Taking patients with the AA genotype as a reference, patients with the AC genotype had a lower risk of developing OP ( OR=0.15, 95% CI: 0.03-0.59). There was a statistically significant difference in the frequency of CC genotype at rs2073618 between the two groups ( χ2=11.30, P=0.001). Taking patients with GG genotype as a reference, patients with CC genotype had a higher risk of developing OP ( OR=7.42, 95% CI: 2.19-27.18). Comparing rs3134069 and rs2073618 loci, there was no significant difference in bone mineral density at each part of the three genotypes (all P>0.05). The multivariate Logistic regression model showed that the AC genotype of rs3134069 ( OR=0.18, 95% CI: 0.03-0.70, P=0.029) was a protective factor for the induction of OP, while GC genotype of rs2073618 ( OR=6.86, 95% CI: 1.57-27.15, P=0.007) were the risk factors for OP in GDM patients. Conclusion:The CC genotype of rs2073618 is significantly positively correlated with the susceptibility to OP in GDM patients.

CAG stimulating regimen in treatment of adult early T cell precursor acute lymphoblastic leukemia complicated with fusarium infection: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical effect of CAG stimulating regimen for refractory adult early T cell precursor acute lymphoblastic leukemia (ETP-ALL) complicated with fusarium infection and the clinical features as well as antifungal strategy of cutaneous fusarium infection.Methods:The diagnosis and treatment of 1 adult patient diagnosed as ETP-ALL complicated with cutaneous fusarium infection in the First Hospital of Jilin University in September 2020 were retrospectively analyzed, and related literatures were reviewed.Results:VICP chemotherapy regimen showed no effectiveness in this patient who was presented with persistent agranulocytosis complicated with cutaneous fusariosis infection. After amphotericin B therapy for infection, he achieved the stable disease and successfully underwent CAG stimulating regimen salvage treatment. The minimal residual disease turned into negative after consolidation chemotherapy based on the myeloid regimen. Finally this patient survived from haploid allogeneic hematopoietic stem cell transplantation after consolidation chemotherapy and fusarium was under the control by using posaconazole as secondary prevention therapy.Conclusions:CAG stimulating regimen can be recommended as reinduction therapy for relapsed/refractory ETP-ALL. Sequential therapy of amphotericin B followed by posaconazole can be a useful antifungal strategy for fusarium infection.

TRPS1 expression in salivary gland-type breast carcinoma and its clinical application / 中华病理学杂志

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol / 中西医结合学报

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5) / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.

Modulation of thalamic network connectivity using transcranial direct current stimulation based on resting-state functional magnetic resonance imaging to improve hypoxia-induced cognitive impairments.

Hypoxic conditions at high altitudes severely affect cognitive functions such as vigilance, attention, and memory and reduce cognitive ability. Hence, there is a critical need to investigate methods and associated mechanisms for improving the cognitive ability of workers at high altitudes. This study aimed to use transcranial direct current stimulation (tDCS) to modulate thalamic network functional connectivity to enhance cognitive ability. We recruited 20 healthy participants that underwent hypoxia exposure in a hypoxic chamber at atmospheric pressure to simulate a hypoxic environment at 4,000 m. Participants received both sham and real stimulation. tDCS significantly improved the participants' emotional status, including depression, fatigue, and energy level. These effects were sustained for more than 6 h (P < 0.05 at the second to fifth measurements). In addition, tDCS enhanced vigilance, but this was only effective within 2 h (P < 0.05 at the second and third measurements). Central fatigue was significantly ameliorated, and cerebral blood oxygen saturation was increased within 4 h (P < 0.05 at the second, third, and fourth measurements). Furthermore, functional connectivity results using the thalamus as a seed revealed enhanced connectivity between the thalamus and hippocampus, cingulate gyrus, and amygdala after tDCS. These results indicated that tDCS increased local cerebral blood oxygen saturation and enhanced thalamic network connectivity in a hypoxic environment, thereby improving vigilance, depression, fatigue, and energy levels. These findings suggest that tDCS may partially rescue the cognitive decline caused by hypoxia within a short period. This approach affords a safe and effective cognitive enhancement method for all types of high-altitude workers with a large mental load.

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

CiteSpace-Based Visualization Analysis of Forensic Research in China from 2010 to 2019 / 法医学杂志

OBJECTIVES@#To analyze the research status of forensic medicine in China from 2010 to 2019, obtain the development trend of forensic medicine and explore the hotspots and research frontiers.@*METHODS@#The forensic medical academic papers published on China National Knowledge Infrastructure (CNKI) database from 2010 to 2019 were collected. CiteSpace 5.7.R1, an information visualization analysis software, was used to analyze publication organizations, authors, keywords, and other elements.@*RESULTS@#The majority of the research institutions were universities, provincial and ministerial scientific research and forensic institutions. Forensic pathology was still an important branch of forensic medicine and a popular research direction. The "polymorphism" and "Y chromosome" had been the research hotspots in recent years. "Medical damage" and "standard" were the most novel studies.@*CONCLUSIONS@#In order to provide scientific basis and research direction for forensic research, this paper analyzes the cooperation network, research hotspots and research innovation in forensic research.

Clinical features and prevention of dislocation after resection and reconstruction of tumors involving pelvic area II / 中华骨科杂志

Objective:To explore the clinical characteristics of dislocation after resection and reconstruction of tumors involving pelvic area II, and to try to propose intraoperative and postoperative techniques to prevent its occurrence.Methods:From March 2011 to March 2021, 122 patients with resection and reconstruction involving pelvic area II were retrospectively analyzed. Among them, 17 had postoperative dislocation, 32 had pelvic area II, and 31 had pelvic area I+II. There were 40 cases in the pelvic area II+III, and 19 cases in the pelvic area I+II+III. There were 49 female patients and 73 male patients; the mean age was 47 years (9-73 years). The Musculoskeletal Tumor Society (MSTS) score of lower extremity patients after reduction was evaluated, and the clinical characteristics of dislocation, such as dislocation direction, dislocation time and reduction method, were counted and analyzed, and feasible prevention measures were analyzed based on the imaging characteristics after resection and reconstruction. dislocation method.Results:Among the 122 patients, there were 17 cases of dislocation, and the dislocation rate was 13.7%. Among them, 12 cases were anterior dislocation, accounting for 70.6% of anterior dislocation; 5 cases were posterior dislocation, and the proportion of posterior dislocation was 29.4%, difference (χ 2=4.52, P=0.033). There were 12 cases of dislocation within 3 months after operation, accounting for 70.6%; 1 case of dislocation occurred in 5 months after operation, and the other 4 cases of dislocation occurred for more than one year. The MSTS score of the dislocation patients after reduction was 56.1±15.6% (20%-80%). Combined with postoperative imaging examinations, the feasible methods for preventing dislocation include: The anteversion angle of the acetabular cup can be appropriately reduced (0°-10°); The acetabular cup can be appropriately shifted to the rear of the rotation center; Appropriately reducing the anteversion angle of the femoral neck prosthesis, the combination of the three can reduce the occurrence of femoral-acetabular prosthesis impingement; at the same time, the affected limb is controlled in a neutral position with strict nail shoes after surgery to avoid the occurrence of external rotation. Conclusion:The dislocation after tumor resection and reconstruction in pelvic area II is mostly anterior dislocation. Postoperative CT scan of the pelvis shows that the space between the neck of the femoral stem prosthesis and the lower edge of the acetabulum is small, which is prone to impingement. If the anteversion angle of the acetabular cup is appropriately reduced, the acetabular prosthesis is appropriately displaced posteriorly, and the anteversion angle of the femoral neck is reduced by 5°, the possibility of femoral-acetabular impingement can be reduced, thereby reducing the risk of postoperative dislocation.

The value of gadoxetate disodium enhanced MRI in the quantitative assessment of liver fibrosis / 中华放射学杂志

Objective:To evaluate the value of quantitative analysis of the relative signal intensity (SI) of liver gadolinium disodium enhanced MRI in the grading of liver fibrosis.Methods:From January 2018 to October 2020, the relevant data of 131 patients who underwent gadoxetate disodium enhanced MRI examination were retrospectively analyzed in Henan Provincial People′s Hospital. All patients had histopathological results. According to the Laennec grading system of liver fibrosis, the patients were classified in F0-F1 (27 cases), F2 (19 cases), F3 (17 cases) and F4 (68 cases). The signal intensity of the liver, erector spinae and spleen were measured before and after the enhancement; and 5 post-contrast relative SI parameters were calculated, including the relative enhancement (RE), liver-to-muscle contrast ratio (LMC), liver-to-spleen contrast ratio (LSC), LMC increase rate, LSC increase rate. The differences of 5 post-contrast relative SI parameters among the different fibrosis grades were compared using one-way analysis of variance. The receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic efficacy of 5 post-contrast relative SI parameters in the diagnosis of clinically significant liver fibrosis (F2-F4), advanced liver fibrosis (F3-F4) and liver cirrhosis (F4).Results:The differences of RE, LMC, LSC, LMC increase rate, LSC increase rate among different liver fibrosis grades were statistically significant (all P<0.001). With the increasing of the degree of liver fibrosis, the RE, LMC increase rate and LSC increase rate showed decreased. ROC results showed that the area under the curve (AUC) of RE, LMC increase rate, LSC increase rate in diagnosing liver fibrosis in all levels were greater than those of LMC and LSC. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of significant fibrosis (F2-F4) were 0.89, 0.86, 0.83, with the sensitivity as 81.7%, 71.2%, 81.7%, and the specificity as 96.3%, 85.2%, and 74.1%, respectively. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of advanced liver fibrosis (F3-F4) were 0.93, 0.88, 0.86, with the sensitivity as 84.7%, 72.9%, 91.8%, and the specificity as 91.3%, 87.0 %, 71.7%; and the AUC values for diagnosing liver cirrhosis (F4) were 0.92, 0.86, 0.85, with the sensitivity as 82.4%, 76.5%, 92.7%, and the specificity as 88.9%, 81.0%, 65.1%, respectively. Conclusion:Gadoxetate disodium enhanced MRI relative SI parameters including RE, LMC increase rate and LSC increase rate might be used as a useful imaging marker in liver fibrosis grading.

Effect of Pien Tze Huang against EV71 / 中国中药杂志

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.