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.

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.

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.

Analysis of the causes of long-standing pelvic anterior sacral space infection and discussion of management techniques / 中华肿瘤杂志

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.

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.

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.

The Clinical Observation of Inflammation Theory for Depression:The Initiative of the Formosa Long COVID Multicenter Study (FOCuS)

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Mid-term clinical outcome of arthroscopic surgery on early knee osteoarthritis in middle-old aged patients / 中国骨伤

OBJECTIVE@#To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy.@*METHODS@#A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group.@*RESULTS@#Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676).@*CONCLUSION@#Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.

Current research status and application prospect of numerical simulation in traditional Chinese medicine drying / 中国中药杂志

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

OBJECTIVE@#Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population.@*METHODS@#A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.@*RESULTS@#All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.@*CONCLUSION@#In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.