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.

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.

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.

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.

Clinical analysis of 252 children with Epstein-Barr virus infection / 中国基层医药

Objective:To investigate the clinical manifestations of Epstein-Barr virus infection in children and the efficacy of interferon combined with ganciclovir.Methods:A total of 252 children with Epstein-Barr virus infection who received treatment in Liaocheng Maternal and Child Health Hospital from June 2018 to February 2020 were included in this study. They were randomly assigned to undergo treatment either with ganciclovir alone (control group, n = 126) or interferon combined with ganciclovir (experimental group, n = 126). General condition, clinical manifestation, clinical outcomes, and clinical efficacy were compared between the two groups. Results:The 252 children with Epstein-Barr virus infection were divided into four groups according to different age brackets: infancy (3.97%), early childhood (53.57%), preschool (28.97%), school age (13.49%). Children at the early childhood and preschool ages accounted for high proportions. Their clinical manifestations included fever, pharyngeal congestion, cervical lymph node swelling, and pharyngeal pain. Children with hepatosplenomegaly accounted for the highest proportion (44.12%) among those at the school age, and children with binocular edema accounted for the highest proportion (10.37%) among those at the early childhood age. The time to defervesce, eyelid edema, and lymph node regression in the experimental group were (3.55 ± 1.58) hours, (3.82 ± 1.17) hours, and (9.55 ± 1.60) hours respectively, which were significantly shorter than those in the control group [(4.40 ± 1.80) hours, (5.33 ± 1.58) hours, (10.44 ± 1.66) hours, t = 3.64, 2.47, 2.67, P < 0.001, P = 0.024, 0.009]. The total response rate was significantly higher in the experimental group than in the control group [96.03% (107/126) vs. 84.92% (121/126), χ2 = 9.03, P = 0.003]. Conclusion:Epstein-Barr virus infection has different clinical manifestations in children at different ages. Interferon combined with ganciclovir is more effective on Epstein-Barr virus infection than ganciclovir alone.

Analysis of the diversity and structural changes of intestinal flora in patients with sepsis / 中华急诊医学杂志

Objective:To explore the diversity and structural changes of intestinal flora in patients with sepsis.Methods:A total of 55 patients were enrolled who visited the Emergency Department of several Grade III-A hospitals from November 2015 to March 2016. Among them, 25 patients with sepsis metthe diagnostic criteria of Sepsis 3.0 and 30 patients had no sepsis. The intestinal flora from all fecal samples was sequenced by 16S rRNA sequencing technology. The diversity and structure changes of the flora were analyzed using Uparse, Qiime, R and LEfSe software.Results:There was no significant difference in sex, age, chronic underlying diseases, and the diversity of intestinal flora between the sepsis and non-sepsis groups (all P>0.05). The structure of intestinal flora was significant different between the two groups ( P<0.05). Abundances of Negativicutes, Selenomonadales, Veillonellaceae, Lachnospiraceae, Faecalibacterium, Hafnia, Lachnoclostridium, Blautia and Ruminococcus in intestinal flora from patients with sepsis were significantly reduced, but those of Bacilli, Coriobacteriia, Lactobacillales, Coriobacteriales, Clostridiaceae, Coriobacteriaceae, Clostridium_sensu_stricto, Collinsella and Collinsella_aerofaciens were significantly increased. Conclusions:There is no change in the diversity of intestinal flora between the sepsis and non-sepsis groups. There are structural changes of intestinal flora in patients with sepsis.

Effect of preoperative waiting time on prognosis of elderly patients with hip fracture / 中国骨伤

OBJECTIVE@#To investigate the relationship between preoperative waiting time and prognosis of elderly patients with hip fracture.@*METHODS@#From January 2014 to December 2018, 333 elderly hip fracture patients undergoing surgery were retrospectively analyzed, including 104 males and 229 females, aged from 60 to 99 years with an average of (77.93±8.49) years, and 183 patients were femoral neck fracture, 150 patients were femoral intertrochanteric fracture. Among them, 269 patients (80.78%) had a clustered preoperative waiting time of 2 to 8 days, and then divided into within 4-day group(91 cases) and over 4-day group(242 cases) according to their preoperative waiting time. The survival situation was followed by telephone, and follow-up time started from fracture admission to the death event, or to the research deadline (December 31, 2019). The Kaplan-Meier method was used for survival analysis, and Cox risk proportion model was used to analyze the independent risk factors of hip fracture in elderly patients.@*RESULTS@#All patients were followed up for 12 to 75 months(means 35 months), 59 patients died and the mortality rate was 17.72%(59/333). Compared with within 4-day group, the mortality rate was higher in over 4-day group[20.66%(50/242) vs. 9.89%(9/91), χ2=5.263, P=0.022]. Multiariable Cox regression analysis showed that preoperative waiting time, age, male and Charlson comorbidity index were independent risk factors for the prognosis of hip fracture in elderly patients (all P<0.05), and every 1-day delay was associated with 5% increase of the risk of death[HR=1.05, 95%CI(1.00-1.10), P=0.045]. Subsequent analyse was stratified according to the Charlson comorbidity index (CCI), and found that over 4-day group had a higher mortality rate in patients with CCI<2, with statistically significant difference(P<0.05).@*CONCLUSION@#For elderly patients with hip fracture, most of hospitals could not complete the hip fracture surgery within 48 hours, we also need to shorten the waiting time before surgery, and thereby improve their prognosis.

Manual therapy combined with posterior percutaneous endoscopic cervical decompression for the treatment of cervical spondylotic radiculopathy / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy and safety of manual therapy combined with posterior percutaneous endoscopic cervical decompression(PECD) in the treatment of intractable cervical spondylotic radiculopathy.@*METHODS@#From May 2016 to May 2018, 23 CSR patients who responded poorly to conservative treatment for at least 6 weeks underwent the combination management. Firstly, the patients received the posterior percutaneous endoscopic cervical decompression routine care for the following 4 weeks and manual therapy for another 4 weeks. A total of 23 patients were followed up, including 14 males and 9 females, the age ranged from 29 to 78 years old with an average of (50.30±12.28) years, the course of disease was 3 to 24 months with an average of (9.74±5.76) months. The lesion segment involved C4,5 in 4 cases, C5,6 in 13 cases, C6,7 in 6 cases. The visual analogue scale (VAS), neck disability index (NDI), changes of cervical physiological curvature and interbody stability, adverse events were observed before and after operation. The follow-up time points were before operation, 1 day after operation and 1, 3 and 6 months after operation.@*RESULTS@#All patients successfully completed the operation and manual treatment for 4 to 8 times. Among the 29 cases, 23 patients were followed up for more than 6 months. There was no spinal cord and nerve root injury during the treatment and follow-up. Operation time was from 80 to 120 min with a median of 90 min;intraoperative blood loss was from 35 to 80 ml with a median of 50 ml. NDI, VAS of neck, shoulder and arm each period after operation were significantly lower than those before PECD(P<0.05), while there were no significant improvement in cervical physiological curvature and target segment intervertebral space height(P>0.05);there was no significant change in interbody stability (P>0.05). After received the manual therapy, NDI significantly decreased (P<0.05), however, there was no significant difference in VAS of neck, shoulder and arm, physiological curvature of cervical spine and intervertebral space height of target segment compared with that before manual treatment (P>0.05);there was no significant change in interbody stability (P>0.05).@*CONCLUSION@#Manual therapy combined with PECD in the treatment of intractable cervical spondylotic radiculopathy can not only quickly improve the symptoms, but also alleviate the residual symptoms after PECD safely and effectively, and can not cause obvious signs of accelerated instability of cervical adjacent segments in the short term.

Current situation and influencing factors of blood glucose management in diabetic patients aged 15 and above in Gansu / 公共卫生与预防医学

Objective To analyze the relationship between follow-up service, personal characteristics, lifestyle and blood sugar management of diabetic patients in Gansu Province, and put forward scientific suggestions on influencing blood sugar management of diabetic patients. Methods Based on the data of the 6th National Health Service Questionnaire, 273 subjects were included. Chi-square test and unconditional logistic regression were used to analyze the blood glucose control and its influencing factors of diabetic patients. Results A total of 39.56% patients' blood sugar status was well controlled. 76.92% patients signed up for family doctor service, and 77.66% patients took hypoglycemic drugs according to the law of doctor's advice. There were significant differences in blood sugar control among patients in different regions, educational levels and occupational types (P <0.05) , logistic regression analysis showed that Hui patients (OR=0.21), doctors without family contract (OR=2.86) and patients taking hypoglycemic drugs intermittently (OR = 6.58). Conclusion The blood sugar control rate of diabetic patients in Gansu is low, and the nationality, contracted family doctors and medication plan affect the blood sugar control level of patients. In order to ensure the high efficiency of follow-up treatment, the related follow-up services provided by primary medical institutions, it is necessary to provide self-management programs that meet the individual characteristics and meet the needs of the disease.

Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.