TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization / 神经科学通报·英文版

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.

Development and validation of a score predicting mortality for older patients with mitral regurgitation / 老年心脏病学杂志（英文版）

OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology / 中国中药杂志

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.

Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema / 中国中药杂志

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

Repair of finger pulp defect with free thenar perforator flap / 中华显微外科杂志

Objective:To investigate the effect of free thenar perforator flap on repair of finger pulp defect.Methods:From September 2019 to November 2021, 79 cases of finger injuries complicated with defects in the pulp of fingers received free thenar perforator flap transfer surgery for reconstruction of finger pulps in the Department of Hand and Foot Surgery, Taizhou Hospital, Zhejiang Province. The patients were 51 males and 28 females, aged from 17 to 52(37.5±5.2) years old. There were 34 finger-pulp defects of index fingers, 15 of middle fingers, 26 of ring fingers and 4 of little fingers. All patients were treated with free thenar perforator flaps sized 2.0 cm×2.5 cm-3.0 cm×3.5 cm. All thenar perforator flaps were pedicled with the perforator artery and subcutaneous superficial vein in the thenar region, and the vessels were anastomosed with the proper palmar digital artery and dorsal digital vein, respectively. At the same time, subcutaneous nerve and proper palmar digital nerve were sutured to reconstruct the sensation of flaps. During the operation, the dominant perforating branch of thenar was found being originated from the superficial palmar branch of radial artery in 27 cases, from the superficial palmar arch in 21 cases, from the perforating branch of metacarpophalangeal proper artery of thumb in 11 cases, from the radial artery in 10 cases and from the main artery of thumb in 10 cases. The origins of nerves within the flaps were found from the superficial branch of radial nerve(24 cases), the terminal branch of lateral cutaneous nerve of forearm(22 cases) and the palmar branch of median nerve(33 cases). The operation time was (96.7±10.7) minutes. The donor site for the flap was closed directly without skin grafting. Most of the follow-up were conducted through the visit of outpatient clinic and the patients from other regions were reviewed via telephone or WeChat.Results:All perforator flaps survived completely and the flap donor sites healed smoothly. Follow-up lasted for (20.5±3.8) months. The reconstructed finger pulp was not bulky and the texture was satisfactory. TPD of the flaps was (5.6±0.9) mm. Only a linear scar left in the flap donor sites without significant affect on thenar function.Conclusion:The vascular anatomy of thenar perforator flap is constant, which helps to regain sensations of the flap. The texture and thickness of the flap are similar to those of the finger. It is ideal for reconstruction of defect of finger pulp.

Correlation between carotid atherosclerosis and subclinical left ventricular dysfunction in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:To investigate the relationship between carotid atherosclerosis(CAS)and subclinical left ventricular(LV)dysfunction in type 2 diabetes mellitus patients with preserved LV ejection fraction(LVEF).Methods:A total of 120 patients with type 2 diabetes mellitus who had LVEF≥50% were selected in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University from June 2021 to October 2021. The global longitudinal strain(GLS)was obtained by two-dimensional speckle tracking echocardiography(STE)to assess subclinical LV systolic function. The mitral ratio of peak early to late diastolic filling velocity(E/A), and mitral velocity to early diastolic velocity of the mitral annulus(E/E′)ratio were obtained by pulsed tissue Doppler echocardiography to assess LV diastolic function. Acrroding to bilateral carotid ultrasound examination, the subjects were divided into normal carotid arteries group( n=46) and CAS group( n=74). Demographics and biochemical parameters were compared between two groups. Binary logistic regression and Pearson correlation analysis were used to evaluate the relationship between CAS and subclinical LV dysfunction. Results:The CAS group had a higher proportion of men, older age, and a longer duration of diabetes than the normal carotid arteries group(all P<0.05). There was no difference in LVEF and GLS between the two groups [normal carotid arteries group vs CAS group, LVEF: (60.72±4.73)% vs(60.07±4.28)%; GLS: (18.24±3.72)% vs(17.81±3.47)%, respectively; both P>0.05]. However, compared with normal carotid arteries group, E/A ratio was decreased and E/E′ ratio was significantly increased in CAS group(both P<0.01). Pearson correlation analysis showed that GLS was not correlated with carotid plaque thickness and carotid intima-media thickness(CIMT; both P>0.05). By contrast, E/E′ ratio was positively correlated with carotid plaque thickness and CIMT(both P<0.05). Binary logistic regression analysis showed that GLS and E/E′ ratio were not associated with CAS( both P>0.05). However, decreased E/A ratio was significantly associated with the existence of CAS( OR=0.09, 95% CI 0.01-0.67, P=0.018). Conclusions:In type 2 diabetes mellitus patients without overt heart failure and with preserved LVEF, the occurrence of CAS is not associated with subclinical LV systolic impairment assessed by GLS, but is significantly associated with LV diastolic dysfunction, and is independent of traditional cardiovascular risk factors.

68Ga production with cyclotron solid target and automated synthesis of 68Ga labeled drugs / 中华核医学与分子影像杂志

Objective:To produce 68Ga and automatically synthesize 68Ga-labeled drugs based on low-energy medical cyclotron solid target system. Methods:68Zn was electroplated on the surface of the target by electrodeposition. According to the principle of 68Zn(p, n) 68Ga nuclear reaction, 68Zn was irradiated by the 10 MeV medical cyclotron solid target system (30 μA, 30 min) to produce 68Ga, and the activity, nuclear purity, half-life and content of metal impurities of purified product were determined. 68Ga-prostate specific membrane antigen (PSMA)-11 and 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) were synthesized automatically using 68Ga respectively, and the quality control analyses of drug properties, concentration, pH, radiochemical purity, sterility and bacterial endotoxin were carried out. Results:The electroplating mass of 68Zn was (43.71±0.87) mg ( n=35), the yield of 68Ga after irradiation was (10.96±0.67) GBq ( n=35), and the measured half-life was (67.64±0.06) min ( n=7). Only 511 keV energy peak was detected by the gamma spectrometer. After purification, (6.85±0.12) GBq ( n=35) of pure 68Ga was obtained, and the purification efficiency was (62.46±0.96)% (non-attenuated correction, n=35). The metal impurity contents of Zn and Fe were (0.18±0.06) and (1.25±0.43) μg/GBq ( n=5), which met the requirements of European Pharmacopoeia. Three batches of 68Ga-PSMA-11 and 68Ga-DOTATATE were automatically synthesized, with the yield, concentration and radiochemical purity of (3.54±0.14) and (2.74±0.20) GBq, (294.97±11.58) and (228.17±16.32) GBq/L, (99.73±0.11)% and (99.45±0.25)%, respectively. Both sterility and bacterial endotoxin were qualified. Conclusion:High-yield and qualified nuclide 68Ga and 68Ga-labeled drugs are successfully prepared through the low-energy medical cyclotron solid target system and the automated purification and synthesis module, which provide a strong guarantee for clinical practice.

Comparison of short-term clinical outcomes and patient satisfaction between robotic-assisted and conventional total hip arthroplasty / 中华骨科杂志

Objective:To compare short-term clinical outcomes and patient satisfaction between robotic-assisted total hip arthroplasty (THA) and conventional THA.Methods:Patient data of unilateral primary THA with the same prosthesis by the same operator due to osteoarthritis, osteonecrosis of the femoral head, and other diseases in Peking University Third Hospital from September 2019 to February 2022 was retrospectively analyzed. Patients were divided into robot-assisted THA group and conventional THA group according to surgical methods. The preoperative general data, operation time, intraoperative complications and other intraoperative data were collected. Anteroposterior X-ray of pelvis and cross-table X-ray of hip were taken. Main outcome measures consisted of total blood loss, blood transfusion rate, hospitalization stay, postoperative complications, and the inclination and anteversion angle of the acetabular cup, while the dislocation rate outside the Lewinnek and Callanan safe zone was also analyzed. Other outcomes measures included visual analogue scale, Harris score, quality of life score (QOL) and satisfaction score.Results:There was no significant difference in gender, age, height, weight, body mass index (BMI), operation side, preoperative blood volume and Harris score between the two groups ( P>0.05); Loosening of positioning screws occurred in 2 patients due to osteoporosis in robot-assisted THA group, so conventional THA was performed. Therefore, 84 cases in robot-assisted THA group and 87 cases in conventional THA group were enrolled in this study at last. There was no significant difference in follow-up time between conventional THA group and robot-assisted THA group (19.7±6.8 months vs. 18.6±5.4 months, t=1.16, P=0.249); The operation time of robot-assisted THA group was longer than that of conventional THA group (106.99±31.91 min vs. 73.79±29.48 min, t=7.07, P<0.001), but there was no significant difference in hospitalization stay between conventional THA group and robot-assisted THA group (6.40±2.40 d vs. 6.49±1.95 d, t=0.26, P=0.796). There was also no significant difference in total blood loss and blood transfusion rate between the two groups ( P>0.05). There was no significant difference in inclination angle (38.79°±6.93° vs. 39.41°±3.01°, t=0.58, P=0.449) and anteversion angle (14.81°±6.49° vs. 13.33°±4.32°, t=3.06, P=0.082) between conventional THA group and robot-assisted THA group, while the percentage in Lewinnek safe zone (96.4% vs. 73.6%, χ 2=15.60, P<0.001) and Callanan safe zone (92.9% vs. 65.5%, χ 2=17.61, P<0.001) was significantly higher in conventional THA than that of robot-assisted THA. There were no significant differences in postoperative VAS, Harris score and QOL score between the two groups ( P>0.05), but the excellent and good rate of Harris score of conventional THA group was lower than that of robot-assisted THA group (83.91% vs. 95.24%, χ 2=5.83, P=0.016); The overall satisfaction of patients in robot-assisted THA group was better than that in conventional THA group ( Z=-3.47, P=0.001), and 95.2% (80/84) of patients in robot-assisted THA group were very satisfied, which was higher than that in conventional THA group (75.86%, 66/87). The satisfaction of patients in robot-assisted THA group on pain relief ( Z=-2.44, P=0.015) and improvement of leisure activity ( Z=-2.12, P=0.034) was better than that in conventional THA group, but there was no significant difference in the satisfaction of ability of doing house work between the two groups ( Z=-0.49, P=0.626). Conclusion:Compared with conventional THA, robot-assisted THA has longer operation time but better short-term clinical outcomes and higher patient satisfaction after surgery.

Predictive value of MR myocardial strain in predicting recent adverse cardiovascular events after primary PCI in patients with acute ST-segment elevation myocardial infarction / 中华放射学杂志

Objective:To investigate the clinical application value of left ventricular myocardial strain obtained by cardiac MR (CMR) in recent major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods:From January 2020 to December 2020, a total of 163 patients successfully underwent primary PCI and underwent CMR examination within one week after surgery at Affiliated Hospital of Xuzhou Medical University. The scan sequences included rapid balance-fast field echo and late-gadolinium enhancement. CVI42 post-processing software was used to analyze and measure the left ventricular myocardial strain indices, including left ventricular global longitudinal strain (GLS), left ventricular global circumferential strain (GCS), and left ventricular global radial strain (GRS). According to the results of the 1-year follow-up after surgery, the patients were divided into the MACE group ( n=28) and the non-MACE group ( n=135). For continuous variables with a normal distribution, the t test of two independent samples was used for comparisons between groups. For continuous variables with an abnormal distribution, the variables were compared and analyzed by the rank sum test. For categorical variables, the χ 2 tests were used for between-group comparisons. Cox regression was used to analyze the prognostic value of myocardial strain on the development of MACE in patients with STEMI. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of myocardial strain parameters, and the optimal cut-off value was evaluated by calculating the Youden index. Results:The GLS, GCS, and GRS of the MACE group were (-10.4±3.3)%, [-11.9 (-14.5, -9.3)]%, and (18.3±6.3)%, respectively, and those of the non-MACE group were (-13.7±3.4)%, [-14.6 (-16.4, -11.7)]%, and (22.3±6.1)%, respectively. The difference between the two groups was statistically significant ( t/ Z=-4.71, -3.04, 3.21, P<0.05). Multivariate Cox regression analysis showed that GLS was an independent predictor of MACE (HR=1.546, 95%CI 1.180-2.027, P=0.002). The ROC curve analysis showed that GLS had the largest area under the curve (AUC) (AUC=0.754, 95%CI 0.658-0.851, P<0.001), with a cut-off value of -12.45%. Its diagnostic sensitivity was 71.4%, and the specificity was 67.4%. The value was better than that of the traditional predictor of STEMI prognosis, namely, left ventricular ejection fraction (AUC=0.680, 95%CI 0.567-0.793, P=0.003). Conclusion:GLS of CMR is an independent predictor of MACE in STEMI patients undergoing primary PCI.

Advances in diagnosis and treatment of medullary thyroid carcinoma complicated with papillary carcinoma / 中华内分泌外科杂志

Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing year by year showing younger trend. The pathological types of thyroid cancer are papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are the two common types of thyroid cancer. Since MTC and PTC have different biological origins, invasiveness and prognosis. Therefore, the occurrence of both medullary carcinoma and papillary carcinoma is very rare and rarely reported in China and abroad and the treatment is challenging. In this paper, we review the pathogenesis, ancillary tests, diagnosis and treatment of this disease, with the aim of providing reference for clinical treatment of patients with medullary thyroid carcinoma complicated by papillary carcinoma.

Research progress of complications related to robotic thyroid surgery-comparison of TORT and BABA approaches / 中华内分泌外科杂志

In recent years, clinical applications of robotic thyroid surgery have been gradually promoted with the continuous improvement of the da Vinci robotic surgical system. Unlike traditional open surgery, robotic thyroid surgery mainly adopts remote access, which has many advantages, such as magnified high-definition 3D view and hand vibration stabilization. The rates and causes of postoperative complications differ due to different approaches, view angles, and operation sequences. This paper presents the literature on both transoral and bilateral areolar axillary approaches in robotic thyroid surgery, focusing on five common complications under both approaches, including laryngeal recurrent nerve injury and hypoparathyroidism, to provide theoretical support for the standardization of robotic thyroid surgery.

Volumetric measurement to diagnose syndesmotic injury in Danis-Weber B type ankle fractures / 国际外科学杂志

Objective:To investigate the change of syndesmotic volume via CT scan in Danis-Weber B type ankle fracture, aiming to provide a non-invasive diagnostic method for Danis-Weber B type ankle fracture combined with syndesmotic injury.Methods:Retrospective analysis was performed on 48 patients with Danis-Weber B type ankle fractures in Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to March 2022, including 30 males and 18 females, aging (43.71±19.41) years. Ankle CT scans and three-dimensional reconstructions were performed before surgery and at the last follow-up, measuring the syndesmotic volume between the tibiotalar joint and 1, 3 and 5 cm above the ankle and compared with each other. Intraoperative exploration was used as the gold standard for the syndesmotic injury. Based on the results of exploration of the syndesmotic injury, patients were divided into simple ankle fracture group (fracture group, 25 cases) and ankle fracture combined with syndesmotic injury group (fracture + ligament group, 23 cases). The sensitivity and specificity of this diagnostic method were statistically evaluated. The assessments at the last follow-up were performed to value the clinical effect of surgery. The metric data conforming to the normal distribution were expressed as mean ± standard deviation ( ± s), and the t-tests were used for comparison between groups. The measurement data of skewed distribution were expressed as quartile M( Q1, Q3), and nonparametric tests were used for intergroup comparison. Counting data were expressed as number of cases and percentage (%), and Chi-square test were used for intergroup comparison. Results:In the fracture group, there were no statistically significant differences of the syndesmotic volume at 1, 3, and 5 cm above the ankle joint before surgery and at the last follow-up ( P=0.219, 0.269, 0.103). On the contrary, the volume above were statistically significant in the fracture + ligament group ( P<0.001). There were statistically significant differences in syndesmotic volume between the two groups at 1, 3, and 5 cm above the ankle joint preoperatively ( P=0.005, 0.004, 0.038). By contrast, there were no statistical differences between the two groups postoperatively ( P=0.082, 0.155, 0.249). For the sensitivity and specificity of Danis-Weber B type ankle fractures combined with syndesmotic injury, they were 92% and 67% at 1 cm above the ankle joint, 69% and 87% at 3 cm above the ankle joint, and 62% and 87% at 5 cm above the ankle joint, respectively. The last follow-up clinical function score indicated a good surgical outcome. Conclusions:Volumetric measurement via CT scan is one of the diagnostic methods for evaluating Danis-Weber B type ankle fracture combined with syndesmotic injurys. Open resection internal fixation combined with elastic fixation of the ankle fracture combined with syndesmotic injurys can significantly reduce the lower tibiofibular volume, and the efficacy is definite.

Efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus in adolescents / 国际外科学杂志

Objective:To investigate the efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus (OLT) in adolescents.Methods:Retrospective case analysis was used. The clinical data and follow-up results of 13 adolescent patients (13 feet) with Hepple Ⅱ OLT were all treated with osteochondral fragment fixation using bioabsorbable pins admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were retrospectively analyzed. There were 7 males and 6 females, with 13 right feet. The age was (14.85±2.23) years old, ranged from 12 to 18 years old. According to the American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) and SF-36 score before operation and at the last follow-up were used to evaluate the efficacy and function of the patients. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; The mearsurement data with skewness distribution were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:Thirteen adolescent patients (13 feet) with Hepple Ⅱ OLT underwent surgery successfully and were followed up for (25.54±9.95) months. All wounds healed by first intention, and no complications such as wound infection and delayed healing occurred. Preoperative AOFAS ankle-posterior foot score, VAS and SF-36 score were 58.62±3.55, 7.00 (6.50, 8.00) and 68.38±4.81, respectively. At the last follow-up, the scores were 97.38±2.73, 1.00 (0.00, 1.00), 91.15±4.28, respectively, and the results were significantly improved at the last follow-up, with the difference between the two groups statistically significant( P<0.05). Conclusion:Osteochondral fragment fixation using bioabsorbable pins which can promote cartilage repair, significantly improve symptoms, and achieve better clinical satisfaction with fewer complications, is a safe and effective surgical treatment option for Hepple Ⅱ OLT in adolescents with satisfactory short-term clinical outcomes.

The synergistic effect of withaferin A combined with cisplatin on cervical cancer and its mechanism / 中国药理学通报

Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

Mechanism of nitidine chloride inducing apoptosis of cervical cancer cells by inhibiting p53 ubiquitination degradation / 中国药理学通报

Aim To investigate the effect of nitidine chloride (NC) on the apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer cell lines HeLa and SiHa were selected as subjects. The cytotoxicity of NC and its inhibitory effect on cell growth were detected by CCK-8 assay and clone formation assay. The effect of NC on the apoptosis of cervical cancer cells was detected by TUNEL assay, and the expression of apoptosis-related proteins was detected by Western blot. The effects of NC on the interaction between p53 and E6AP protein, the level of p53 ubiquitination modification and the stability of p53 protein in cervical cancer cells were analyzed by immunoprecipi-tation assay, ubiquitination assay and Western blot assay. Results NC could significantly inhibit the proliferation and induce apoptosis of cervical cancer cells. NC could inhibit the interaction between tumor suppressor protein p53 and E6AP in cervical cancer cells, reduce the level of p53 ubiquitination modification, delay the degradation of p53 and increase the expression level of p53 protein. Conclusions NC can inhibit the ubiquitination and degradation of p53, improve the expression level of p53 protein, restore its tumor suppressor function, and thus play an anti -cervical cancer role.

Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma / 国际口腔科学杂志·英文版

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36+ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36+ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.

Research progress of intravesical recurrence after radical resection of upper tract urothelial carcinoma / 现代泌尿外科杂志

Urothelial carcinoma (UC) is the second most common genitourinary tumor, and upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of UC. Intravesical recurrence (IVR) occurs in 22% to 47% of patients after radical resection. This article reviews the mechanism, characteristics, related risk factors, regular bladder monitoring, diagnosis and treatment, and preventive measures of IVR, hoping to provide reference for clinical work.

External rhinoplasty based on the classification of alar retraction associating with exposure of the nostrils / 中华耳鼻咽喉头颈外科杂志

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.

Imaging measurement and analysis of related indexes of variation of femoral head rotation center / 中国骨伤

OBJECTIVE@#To provide guidance for hip replacement by analyzing the variation of femoral head rotation center in different hip diseases.@*METHODS@#A total of 5 459 patients were collected from March 2016 to June 2021, who took positive and proportional plain films of both hips for various reasons. The relative position between the rotation center of the femoral head and the apex of the greater trochanter was measured. The positive variation is more than 2 mm above the top of the great trochanter, and the negative variation is more than 2 mm below the top of the great trochanter. A total of 831 patients with variation of femoral head rotation center were collected and were divided into 4 groups according to different diseases, and the variation was counted respectively. There were 15 cases in the normal group involving 10 cases of positive variation and 5 cases of negative variation. There were 145 cases of avascular necrosis of femoral head involving 25 cases of positive variation and 120 cases of negative variation. There were 346 cases of congenital hip dysplasia involving 225 cases of positive variation(including 25 cases of typeⅠ, 70 cases of type Ⅱ, 115 cases of type Ⅲ and 15 cases of type Ⅳ), and 121 cases of negative variation(including 50 cases of crowe typeⅠ, 60 cases of typeⅡ, 10 cases of type Ⅲ and 1 case of type Ⅳ). There were 325 cases of hip osteoarthritis group involving 45 cases of positive variation and 280 cases of negative variation.@*RESULTS@#There was significant difference in variation of femoral head rotation center among the four groups(P<0.05). There was significant difference in variation of femoral head rotation center among different types of congenital hip dysplasia(P<0.05). There were significant differences in cervical trunk angle and eccentricity among different variations of femoral head rotation center(P<0.05).@*CONCLUSION@#The variation of femoral head rotation center is related to cervical trunk angle and eccentricity. The variation of femoral head rotation center is an important factor in hip diseases. The variation of femoral head rotation center is different in different hip diseases. Avascular necrosis of the femoral head and osteoarthritis of the hip were mostly negative variations. With the aggravation of congenital hip dysplasia, the variation of femoral head rotation center gradually changed from negative variation to positive variation.The variation of femoral head rotation center should be paid attention to in the preoperative planning of hip arthroplasty. It is of great significance to select the appropriate prosthesis and place the prosthesis accurately.

Propensity score-matched study of uni-condylar arthroplasty in elderly patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of unicompartmental knee arthroplasty (UKA) in the treatment of knee osteoarthritis in patients over 75 years old.@*METHODS@#The clinical efficacy of primary fixed platform UKA in patients with osteoarthritis, was retrospectively analyzed from October 2014 to November 2020. Age, body mass index (BMI), range of motion (ROM), preoperative joint function score, the quality of life score and other preoperative indicators were measured by propensity score matching (PSM). The patients were divided into elderly group (≥75 years old) and control group (<75 years old). Oxford knee score(OKS), Western Ontario McMaster Universities osteoarthritis index(WOMAC), Short Form-12 including physical component summary (PCS), mental component summary(MCS), minimal clinically important difference(MCID ) and clinical complications were evaluated preoperatively and postoperatively.@*RESULTS@#A total of 514 patients were analyzed, 428 patients fulfilled the inclusion criteria. A propensity-score matching study was conducted to eliminate confounding factors. After 1∶2 propensity match, there were 84 patients in elderly group (≥75 years), age ranged from 75 to 88 years old, with an average of (78.79±3.08) years old, and 168 patients in control group (<75 years), age ranged from 47 to 74 years old, with an average of (64.10±5.96)years old. The follow-up duration of two groups ranged from 12 to 84 months with an average of (29.35±16.52) months in elderly group, and 12 to 85 months with an average of (31.83±17.34) months in control group. There was only significant difference in age between the elderly and control groups preoperatively (P<0.01). Postoperatively, the elderly group showed significantly higher WOMAC (P<0.01) and lower SF-12 PCS scores (P<0.01) as compared to the control group. There was no significant difference between the elderly group and the control group in knee range of motion, OKS and the proportion of each scoring system reaching the minimum clinical difference value (P>0.05). In the aspect of preperative complications, the elderly group exhibited more surgical site complications and postoperative delirium compared to control group(P<0.05). The differences in other indicators including deep vein thrombosis, acute urinary retention, cardiovascular events, cerebrovascular events and radiolucent lines around prothesis were not statistically significant(P>0.05).@*CONCLUSION@#UKA in the treatment of elderly patients over 75 years old with knee osteoarthritis was safe and feasible, and could obtain satisfactory short-term efficacy.