Mitigation of retinol-induced skin irritation by physiologic lipids: Evidence from patch testing.

BACKGROUND: There is a dearth of effective treatments to counter retinol-induced skin irritation. OBJECTIVE: This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol. METHODS: An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double-blind, and vehicle-controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post-test. Subsequently, a 4-week consumer in-use test, randomized and double-blind in nature, was executed to substantiate the soothing effects of PLG. RESULTS: Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol-induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol-induced discomfort. The subsequent consumer in-use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone. CONCLUSION: To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol-induced irritation. Given their capacity to counter retinol-induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia-CR a* value can serve as a robust objective measure for interpreting patch test outcomes.

The prediction of influenza-like illness using national influenza surveillance data and Baidu query data.

BACKGROUND: Seasonal influenza and other respiratory tract infections are serious public health problems that need to be further addressed and investigated. Internet search data are recognized as a valuable source for forecasting influenza or other respiratory tract infection epidemics. However, the selection of internet search data and the application of forecasting methods are important for improving forecasting accuracy. The aim of the present study was to forecast influenza epidemics based on the long short-term memory neural network (LSTM) method, Baidu search index data, and the influenza-like-illness (ILI) rate. METHODS: The official weekly ILI% data for northern and southern mainland China were obtained from the Chinese Influenza Center from 2018 to 2021. Based on the Baidu Index, search indices related to influenza infection over the corresponding time period were obtained. Pearson correlation analysis was performed to explore the association between influenza-related search queries and the ILI% of southern and northern mainland China. The LSTM model was used to forecast the influenza epidemic within the same week and at lags of 1-4 weeks. The model performance was assessed by evaluation metrics, including the mean square error (MSE), root mean square error (RMSE) and mean absolute error (MAE). RESULTS: In total, 24 search queries in northern mainland China and 7 search queries in southern mainland China were found to be correlated and were used to construct the LSTM model, which included the same week and a lag of 1-4 weeks. The LSTM model showed that ILI% + mask with one lag week and ILI% + influenza name were good prediction modules, with reduced RMSE predictions of 16.75% and 4.20%, respectively, compared with the estimated ILI% for northern and southern mainland China. CONCLUSIONS: The results illuminate the feasibility of using an internet search index as a complementary data source for influenza forecasting and the efficiency of using the LSTM model to forecast influenza epidemics.

Ultrasonic-Assisted Surface Finishing of STAVAX Mold Steel Using Lab-Made Polishing Balls on a 5-Axis CNC Machining Center.

The inconvenience of conventional wool ball polishing is that the surface finishing process should be equipped with a slurry container. The main objective of this research is to develop an ultrasonic-assisted surface finishing process for STAVAX mold steel on a 5-axis CNC machining center, by using new lab-made rubber polishing balls containing the abrasive aluminum oxide instead of the traditional wool ball polishing. In total, five types (type A to type E) of new rubber-matrixed polishing balls with a composite of nitrile butadiene rubber (NBR), an abrasive of aluminum oxide, and an additive of silicon dioxide have been developed. The performance of the composites with different grain sizes (0.05 µm to 3 µm) and concentrations of the abrasive of aluminum oxide have been investigated. The effects of multiple polishing passes on the surface roughness improvement for the lab-made polishing balls have also been investigated in this study. A surface roughness of Ra 0.027 µm on average was achieved by using the multiple polishing process of E-C-B-A. The volumetric wear of the lab-made polishing balls, using ultrasonic vibration-assisted polishing, can be improved from about 12.64% (type A) to 65.48% (type E) compared with the non-vibration-assisted polishing. The suitable combination of the ultrasonic vibration-assisted polishing parameters were an amplitude of 10 µm, a frequency of 23 kHz, a spindle speed of 5000 rpm, a feed rate of 60 mm/min, a stepover of 20 µm, a penetration depth of 180 µm, and a polishing pass of E-C-B-A, based on the experimental results. The surface roughness improvement on a test carrier with a saddle surface has also been presented by using the ultrasonic vibration-assisted polishing with the lab-made polishing balls.

Ultrasound-Guided Thoracic Paravertebral Block Using Paraventricular Oblique Sagittal (POS) Approach for the Treatment of Acute Herpes Zoster: A Two-Blind Randomized Controlled Trial.

INTRODUCTION: The aim of this work is to examine the efficacy and benefits of ultrasound (US)-guided thoracic paravertebral block (TPVB) using paraventricular oblique sagittal (POS) approach for the treatment of herpes zoster related acute pain (ZAP) and its preventive effects on post-herpetic neuralgia (PHN). METHODS: A total of 136 patients suffering from ZAP within 2 weeks of rash onset were randomly allocated to transverse short axial approach (TSA) and paraventricular oblique sagittal (POS) group in 1:1 ratio. All patients received a standard antiviral treatment and rescue analgesics besides TPVB. Primary outcome was HZ illness burden (HZ-BOI) measured by a severity-by-duration composite pain assessment during 30 days. The non-inferiority margin (NIM) was set at - 10. Secondary outcomes included visual analog pain scores (VAS) and Kolcaba's General Comfort Questionnaire discomfortable scores (GCQ) during block needle insertion, quality of life (QoL), and PHN incidence during follow-up. Adverse events were also recorded. RESULTS: VAS pain scores (30 (IQR: 20, 40) vs. 65 (IQR: 45, 90), p < 0.001) and GCQ discomfortable scores (p < 0.001) were significantly lower in the POS group during needle insertion. The POS approach was not inferior to the proved TSA method in terms of BOI-30AUC when the lower limit of 95% confidence interval (CI) of two mean differences (13.54 (95% CI - 3.55, 30.63)) lay within the NIM. There were no differences between the two groups in BOI-30-90AUC, and BOI-90-180AUC (p = 0.260 and 0.182). Greater QoL improvement and lower PHN incidence were comparable between the two groups. No serious adverse events occurred. CONCLUSIONS: US-guided TPVB using less-invasive POS technique was as an optimal early intervention to reduce ZAP and a possible preventive strategy for PHN. TRIAL REGISTRATION: The study was retrospectively registered in the Chinese Clinical Trial Registry on November 15, 2022 (ChiCTR2200065783).

Advances in the regulation of inflammasome activation by GBP family in infectious diseases.

Guanylate-binding proteins (GBPs) are a subfamily of interferon-inducible proteins that undertake distinct roles in the the context of bacteria, virus, chlamydia and parasites infections. These proteins exert a notable influence on the progression and outcomes of infectious diseases. Within the realm of host cell-autonomous immunity against pathogens, GBPs have been identified as the regulators of pyroptosis through canonical and noncanonical inflammasome activation pathways. In this review, we summarize the structure and evolution of GBP family members, the canonical and noncanonical inflammasome activation pathways, the roles of GBPs in regulating inflammasome activation, and the mechanisms of GBPs affecting infections induced by different pathogens. We hope to provide new basic research clues for the pathogenesis and diagnosis and treatment of infectious diseases.

Mechanism of high-salt diet up-regulating TMEM16A-induced cerebral arterial remodeling in C57BL/6J mice / 中国药理学通报

Aim To investigate the mechanism of high salt-induced cerebral artery remodeling in mice by up-regulating TMEM16A. Methods Forty C57BL/6J mice were randomly divided into four groups (10 per group, 8 weeks of intervention), namely, blank control group (normal diet), low-salt group (2% high salt diet), medium-salt group (4% high salt diet) and high-salt group (8% high salt diet). HE staining was used to observe the morphological changes of cerebral arteries; blood vessel permeability test was used to compare the color and absorbance value of brain tissue. Immunofluorescence was employed to detect TMEM16A expression in cerebral arteries of mice in each group; PCR and Western blot were applied to detect the mRNA and protein expression of TMEM16A in cerebral arterial tissues; whole-cell patch clamp was use to record the calcium-activated chloride channel (CaCC) currents of mouse cerebral artery smooth muscle cells in each group. Results HE results showed that 2%, 4%, and 8% high salt diet could concentra-tion-dependently induce cerebral arterial wall thickening and lumen stenosis in C57BL/6J mice. The permeability test found that compared with the control group, the absorbance value of the brain tissue of the mice in the 2%, 4% and 8% high salt groups increased significantly. The results of isolated muscle tension showed that compared with the control group, the systolic response of isolated cerebral arteries to 60 mmol • L

The effect of enhanced recovery after surgery protocols combined with laparoscopic radical cystectomy with intracorporeal urinary diversion / 中华泌尿外科杂志

Objective:To explore the effect of enhanced recovery after surgery (ERAS) protocols in patients undergoing laparoscopic radical cystectomy (LRC) and intracorporeal urinary diversion (ICUD).Methods:A total of 83 patients who received LRC+ ICUD in Beijing Chaoyang Hospital from March 2014 to September 2020, were divided into 2 groups based on different perioperative management, including 29 ERAS cases and 54 conventional recovery after surgery (CRAS) cases. The ERAS group included 26 males and 3 females , with an average age of (62.07 ± 9.26) years. There were 26 patients with ASA class Ⅰ-Ⅱ, 3 patients with ASA class Ⅲ, 4 patients received neoadjuvant chemotherapy, and 7 patients had a history of abdominal surgery in ERAS group. The CRAS group included 44 males and 10 females , with an average age of (61.59 ± 10.16) years. There were 50 patients with ASA class Ⅰ-Ⅱ, 4 patients with ASA class Ⅲ, 9 patients received neoadjuvant chemotherapy, and 10 patients had a history of abdominal surgery in CRAS group. There were no statistically significant differences in the baseline characteristics between the two groups. The patients in both groups underwent LRC+ ICUD procedures. The perioperative results and complications between the two groups were compared.Results:In the ERAS group, there were 20 patients who underwent Bricker ileal conduit surgery and 9 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 3, 3, 7, 7, 5 and 4 cases in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 23, 2, 3 and 1 patient with pathological stage N 0, N 1, N 2 and N 3, respectively. Pathological diagnosis included 3 cases of low-grade urothelial carcinoma, 24 cases of high-grade urothelial carcinoma, and 2 cases of other histological subtypes. In the CRAS group, there were 31 patients who underwent Bricker ileal conduit surgery and 23 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 5, 3, 12, 9, 15 and 10 patients in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 35, 6, 7 and 6 patients with pathological stage N 0, N 1, N 2, and N 3, respectively. Pathological diagnoses included 6 cases of low-grade urothelial carcinoma, 45 cases of high-grade urothelial carcinoma, and 3 cases of other histological subtypes. There were no statistically significant differences ( P>0.05) in surgical methods, pathological staging, or pathological types between the ERAS and CRAS groups. ERAS group presented less albumin loss [(25.73±8.63)% vs. (32.63±9.05)%, P=0.001], shorter hospital stay [9(7, 13)d vs. 12(9, 16)d, P=0.006], less 30-day overall complications [55.2% (16/29) vs. 83.3% (45/54), P=0.009]. In multivariable analysis, maximum albumin loss≥20% was independently associated with 30-day minor complications ( P=0.049), and maximum albumin loss ≥25% was independently associated with hospital of stay≥10 days ( P=0.038), respectively. Conclusions:For patients who received LRC+ ICUD, ERAS was associated with reduced perioperative albumin loss, shorter length of stay, less 30-day complications, accelerated recovery time, improved clinical outcome and less albumin injection.

High mobility group box-1 inhibition reduces expression of matrix metalloproteinase-9 in astrocytes in rats after spinal cord injury / 中华创伤骨科杂志

Objective:To investigate the role and underlying mechanisms of inhibiting high mobility group box-1 (HMGB1) in the expression of matrix metalloproteinase-9 (MMP-9) in spinal cord astrocytes (AS) in rats after spinal cord injury (SCI).Methods:After an SCI model was established in Sprague-Dawley (SD) rats using a modified Allen's Weight-Dropping method and ethyl pyruvate (EP) or glycyrrhizin (GL) was used to inhibit the effect of HMGB1, the rats were divided into a sham group, an SCI group, an SCI+EP (50 mg/kg) group, and an SCI+GL (100 mg/kg) group. The expression levels of glial fibrillary acid protein (GFAP) and MMP-9 in spinal cord AS were observed. After the spinal cord AS in SD rats was cultured and incubated by the oxygen-glucose deprivation/reoxygenation (OGD/R) procedure, the expression of MMP-9 protein was detected at 6 h/R 6 h, 12 h, 24 h, and 48 h after OGD. The time point with the highest expression was chosen in the subsequent experiments as an OGD/R group. HMGB1 was inhibited by HMGB1 shRNA or EP to observe the effect of HMGB1 on the expression of MMP-9 protein in AS treated with OGD/R. Then, toll-like receptor 4 (TLR4) inhibitor, TIR-domain-containing adaptor inducing interferon- β (TRIF) inhibitor, and nuclear factor-kappa B (NF- κB) inhibitor were used to investigate the effects of TLR4/TRIF/NF- κB signaling pathway during the regulation of HMGB1 on MMP-9 in vitro. Results:Western blot showed that the expression of MMP-9 protein in the spinal cord was significantly increased in rats at 1 d after SCI, and the expression of MMP-9 protein in the SCI+EP group and the SCI+GL group was significantly lower than that in the SCI group ( P<0.001). Immunofluorescence showed that GFAP and MMP-9 proteins were co-localized in the spinal cord after SCI, and the expression of GFAP and MMP-9 proteins in the SCI+EP and SCI+GL groups was significantly lower than that in the SCI group ( P<0.05). Since the expression of MMP-9 protein in the spinal cord AS cultured in vitro was significantly higher in the OGD 6h/R 12h group than that in the normal group and the OGD 6h/R 6h, 24, and 48 h groups, the OGD 6h/R 12h was taken as the OGD/R group. The MMP-9 protein expression in AS in the OGD/R+HMGB1 shRNA group and the OGD/R+EP group was significantly lower than that in the OGD/R group ( P<0.001). In the cultured AS, moreover, inhibiting TLR4, TRIF, and NF- κB reduced MMP-9 protein expression after OGD 6 h/R 12 h when compared with that in the OGD/R group ( P<0.001). Conclusions:HMGB1 inhibition may result in a reduction in MMP-9 expression both in the spinal cord AS in SCI rats and in AS after OGD/R treatment in vitro. HMGB1 may regulate MMP-9 protein expression in AS after OGD/R treatment via the TLR4/TRIF/NF- κB signal pathway.

Research progress of vitamin D, monocyte chemoattractant protein-1 and Hashimoto's thyroiditis / 中国医师杂志

Hashimoto thyroiditis (HT) is one of the most common autoimmune thyroid disease, and its pathogenesis has not been fully clarified at present. Most people believe that it is induced by mental stress, overwork, infection, stress, environmental pollution, unreasonable diet structure (such as high iodine diet) and other factors on the basis of genetic defects and genetic susceptibility. Vitamin D is a steroid hormone that maintains the balance of calcium and phosphorus metabolism in the body, regulating bone and mineral salt metabolism. Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine CC family. It binds to chemokine receptor (CCR) and participates in immune inflammatory response. In recent years, more and more studies have found that vitamin D and MCP-1 are involved in the occurrence and development of many immune diseases, including Hashimoto thyroiditis. This article reviews the new research progress of the role of vitamin D and MCP-1 in Hashimoto thyroiditis.

Matrix Stiffness Affects Mitochondrial Heterogeneity of Tibial Plateau Chondrocytes in Knee Osteoarthritis / 医用生物力学

Objective To investigate the difference of matrix stiffness in different regions of tibial plateau in osteoarthritis (OA) and its effects on morphology of the cartilage and mitochondria. Methods The tibial plateau cartilage specimens of OA were obtained for nanoindentation test, transmission electron microscopy and histological analysis. The stiffness of cartilage matrix in different regions of OA tibial plateau was detected by nano-indentation. The morphology of cartilage mitochondria in different regions was observed by transmission electron microscopy, and the changes of mitochondrial plane area, shape and ridge volume density were quantitatively analyzed. Cartilage injury in different regions of OA tibial plateau was observed by histological staining. Results The cartilage of OA tibial plateau showed regional heterogeneity, and the cartilage and mitochondria on medial side of varus knee OA were more severe, and the matrix stiffness was higher. The OA scores were positively correlated with matrix stiffness. There was also a significant correlation between OA scores and mitochondrial morphology: the higher OA scores, the larger and rounder mitochondrial plane area, and the lower cristae volume density. Conclusions The differences of tibial plateau revealed the correlation between cartilage matrix stiffness, OA scores and mitochondrial morphological parameters. The increased cartilage matrix stiffness may be the main cause of chondrocyte mitochondrial injury, and further aggravate the progression of OA.

Clinical features of fundus lesions of 74 patients with acquired immunodeficiency syndrome in Shenyang / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and factors of fundus lesions in patients with acquired immunodeficiency syndrome(AIDS)in Shenyang and the relationship between fundus lesions and CD4+T cell count.METHODS: Retrospective case study. A total of 74 cases with AIDS who were treated in the Central Hospital of Liaoning Electric Power Supply Co., Ltd., from January 2021 to December 2021 were selected. The fundus manifestation and CD4+T cell count of the patients were analyzed.RESULTS: The total detection rate of fundus lesions in AIDS patients was 58%. CD4+T cell count in the patients with fundus lesions was significantly lower than that in the patients with normal fundus [29(6, 55)/μL vs. 76(35, 103)/μL, P<0.01]. The rate of fundus lesions was the highest in the patients with CD4+T cell count ≤ 50/μL(74%). Logistic regression analysis showed that as the CD4+T cell count increased, the incidence of fundus lesions decreased(OR=0.977, 95%CI 0.964～0.991, P<0.01).CONCLUSION: Fundus lesions in AIDS patients related to CD4+T cell count. Decreasing CD4+T cell count was a risk factor of fundus lesions for AIDS patients. Routine fundus examination is important for the early diagnosis of fundus lesions in AIDS patients.

Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy.@*METHODS@#Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation.@*RESULTS@#There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024).@*CONCLUSION@#The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Clinical and genetic characteristics of 12 cases of Loeys-Dietz syndrome / 中华医学遗传学杂志

OBJECTIVE@#To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes.@*METHODS@#Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed.@*RESULTS@#The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously.@*CONCLUSION@#Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.

Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism / 中华医学杂志(英文版)

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.

Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism / 中国针灸

OBJECTIVE@#To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment.@*METHODS@#The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.

Microcatheter-guided compartment packing of acutely ruptured complex intracerebral aneurysms (ARCIAs): Preliminary experience and technical note.

Objective: We present our initial experience using the microcatheter-guided compartment packing (MCP) technique for endovascular embolization of acutely ruptured complex intracerebral aneurysms (ARCIAs) and evaluate the safety, feasibility, and efficiency of this technique. Methods: This retrospective, single-center study included 28 patients who underwent coil embolization using the MCP technique for ARCIAs at our institution between January 2021 and January 2022. The MCP technique was the placement of microcatheters in different compartments within the aneurysm to deploy the coils simultaneously or sequentially. Patient demographics, aneurysm characteristics, procedural parameters, grade of occlusion, complications, and clinical results were analyzed. The clinical outcomes were evaluated with modified Rankin Scale (mRS) scores. Results: Of the 28 patients successfully treated with the MCP technique, 24 (85.7%) aneurysms were considered as complete occlusions (Raymond I) based on the immediate postembolization angiogram results. Complications occurred in 2/28 treatments, including guidewire perforation with subarachnoid hemorrhage and cerebral vasospasm-related cerebral infarction. An angiography follow-up demonstrated complete occlusion in 25/28 aneurysms. Twenty-six (92.9%) patients had favorable 90-day outcomes (mRS 0-2) after the endovascular coil embolization. Conclusion: The MCP technique is simple, safe, and effective, achieving good packing density and initial occlusion rate when used to treat ARCIAs.

Mechanical Thrombectomy with Tandem Double Stent Retriever in Combination with Intermediate Catheter Aspiration for Refractory Severe Hemorrhagic Cerebral Venous Sinus Thrombosis.

OBJECTIVE: We aimed to describe the initial experience of mechanical thrombectomy using tandem double stent retrievers combined with intermediate catheter aspiration to treat refractory severe hemorrhagic (SH)-cerebral venous sinus thrombosis (CVST). METHODS: All refractory SH-CVST patients treated with mechanical thrombectomy using tandem double stent retriever (SR) combined with intermediate catheter aspiration (MT-TDSA) in our institution were retrospectively reviewed. MT-TDSA is a technique that fully engages the clot with double SRs and retrieves the clot using a double SR in combination with aspiration from an intermediate catheter. Demographics, clinical manifestation, medical history, the location of the occluded venous sinus, intraoperative details, procedure-related complications, and modified Rankin Scale (1, 6, 12 months postoperatively) were collected and analyzed. RESULTS: Fourteen patients (median age, 43 years) with refractory SH-CVST were treated with MT-TDSA between January 2016 and January 2020. Ten of 14 (71.4%) had a successful intraoperative recanalization rate (>90%) using MT-TDSA. No procedure-related complications occurred. Eleven patients had good clinical outcomes (modified Rankin Scale score 0-2 at 12 months postoperatively). CONCLUSIONS: MT-TDSA for refractory SH-CVST might improve clot-capturing ability and remove blood clots from cerebral venous sinuses effectively and safely, achieving good clinical outcomes.

Sex Differences in Obesity and Cognitive Function in Chinese Elderly Patients With Chronic Schizophrenia.

Background: It is well known that schizophrenia is associated with sex differences. However, no study has explored the sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia. Objective: This study aimed to compare sex differences in obesity and cognitive function in elderly Chinese individuals with schizophrenia. Methods: A total of 304 elderly patients with schizophrenia and 130 sex- and age-matched healthy controls from the community were recruited. Demographic, clinical, and lipid parameters were collected for all subjects. The Montreal Cognitive Assessment (MoCA) was used to assess the global cognitive functions of the participants, while the Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathological symptoms in patients with schizophrenia. Results: Of the patients with schizophrenia, the prevalence of obesity in men and women was 11.7% (19/163) and 21.3% (30/141), respectively. The score (14.51 ± 6.504) of MOCA in elderly male patients with schizophrenia was significantly higher than that (11.40 ± 6.822) in female patients. There was a positive correlation between the MOCA scores and body mass index (BMI) (r=0.206, p=0.018) in male elderly patients with schizophrenia. Conversely, the MOCA scores of female elderly patients with schizophrenia did not correlate with BMI (p>0.05). However, we found no sex differences in obesity and cognition among control older adults. Conclusions: Our findings suggest that there are significant sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia.

An Asia-specific variant of human IgG1 represses colorectal tumorigenesis by shaping the tumor microenvironment.

Emerging studies have focused on ways to treat cancers by modulating T cell activation. However, whether B cell receptor signaling in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here, we report that an Asia-specific variant of human IgG1 containing a Gly396 to Arg396 substitution (hIgG1-G396R) conferred improved survival of patients with colorectal cancer (CRC). Mice with knockin of the murine functional homolog mIgG2c-G400R recapitulated the alleviated tumorigenesis and progression in murine colon carcinoma models. Immune profiling of the TME revealed broad mobilizations of IgG1+ plasma cells, CD8+ T cells, CD103+ DCs, and active tertiary lymphoid structure formation, suggesting an effective antitumor microenvironment in hIgG1-G396R CRC patients. Mechanistically, this variant potentiated tumor-associated antigen-specific (TAA-specific) plasma cell differentiation and thus antibody production. These elevated TAA-specific IgG2c antibodies in turn efficiently boosted the antibody-dependent tumor cell phagocytosis and TAA presentation to effector CD8+ T cells. Notably, adoptive transfer of TAA-specific class-switched memory B cells harboring this variant exhibited therapeutic efficacy in murine tumor models, indicating their clinical potential. All these results prompted a prospective investigation of hIgG1-G396R in patients with CRC as a biomarker for clinical prognosis and demonstrated that manipulating the functionality of IgG1+ memory B cells in tumors could improve immunotherapy outcomes.