"Very early" intrahepatic cholangiocarcinoma (≤ 2.0 cm): MRI manifestation and prognostic potential.

AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.

Secondary infections of COVID-19 in schools and the effectiveness of school-based interventions: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis explored secondary infections of SARS-CoV-2 and the effectiveness of non-pharmaceutical interventions (NPIs) in school settings, with the aim of providing a reference to formulate scientific prevention and response strategies for similar major public health emergencies in specific settings. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Systematic searches were conducted in PubMed, Web of Science and the Cochrane Library through to 1 August 2022 using the following key search terms: COVID-19, SARS-CoV-2, secondary attack rate, school, transmission, etc. The IVhet model was used for the meta-analysis, and the I2 index and Cochran's Q-test were used to assess heterogeneity. Publication bias was examined using Doi plot, Galbraith plots and Luis Furuya-Kanamori index. Prevalence Critical Appraisal Tool was used to assess the quality of the included articles, while Grading of Recommendations Assessment, Development, and Evaluation was used to rate the quality of the evidence. Subgroup analyses were conducted to explore the potential source of heterogeneity. RESULTS: Thirty-four studies involving 226,727 school contacts and 2216 secondary cases were included in this study. The pooled secondary attack rates (SARs) of close contacts, staff contacts and student contacts were 0.67% (95% confidence interval [CI]: 0.11, 1.56), 0.79% (95% CI: 0.00, 6.72) and 0.50% (95% CI: 0.00, 4.48), respectively. Subgroup analysis suggested that multiple or specific combinations (e.g. the combination of contact restriction and hygiene action) of NPIs appeared to be associated with lower SARs. CONCLUSIONS: The SAR of SARS-CoV-2 was low in schools. Multiple or specific combinations of prevention strategies appear to mitigate SARS-CoV-2 transmission in school settings. These findings provide a basis for continuous improvement of response strategies to major public health emergencies in the school environment.

[Thoughts and suggestions on digital services to enhance the level of vaccination management].

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

[UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children].

Objective: To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Methods: Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Results: Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G > A accounted for 37.5% (6/16), c.1456T > G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin (t = 5.539, P < 0.05), and indirect bilirubin (t = 5.312, P < 0.05). However, there was no significant difference in direct bilirubin levels (t = 1.223, P > 0.05) and age of onset (t = 0.3611, P > 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T > G homozygous mutations had the highest serum bilirubin levels. Conclusion: The common pathogenic variants of the UGT1A1 gene sequence are c.1456T > G, c.211G > A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

[Short-term outcomes of all-inside endoscopic running locked stitch technique for acute achilles tendon ruptures].

Objective: To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures. Methods: This is a retrospective case series study. Forty-eight cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022 at Department of Orthopaedics, General Hospital of Central Theater Command. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m2 (range: 18 to 26 kg/m2); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon was performed to observe the regeneration of Achilles tendon during follow-up. Surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired sample t test. Results: The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at 12 months after operation. The median ATRS score (M(IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs. (17.4±2.6)°, t=1.92,P=0.062) and heel rise height ((14.2±1.7)cm vs. (14.4±1.5)cm, t=1.71,P=0.094). No nerve injury, infection, deep vein thrombosis and re-rupture was encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions: All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Effect of SLC7A11 gene downregulation on the gefitinib resistance of lung adenocarcinoma PC9/GR cells and its mechanism].

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 µmol/L and 64.01 µmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) µmol/mg vs. (82.18±7.77) µmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.

[Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma].

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

[CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy].

Objective: To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy. Methods: A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis. Results: A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included"original_ngtdm_Strength"(0.49 vs. -0.61,P=0.006), "wavelet-HLH_glszm_ZonePercentage"(0.67 vs. -0.22,P=0.024),"wavelet-LHL_ngtdm_Strength"(1.20 vs. -0.51,P=0.002), "wavelet-HLL_gldm_LargeDependenceEmphasis"(-0.84 vs. 0.19,P=0.002), "wavelet-HLH_glcm_Id" (-0.30 vs. 0.43,P=0.037),"wavelet- HLH_glrlm_RunPercentage"(0.45 vs. -0.01,P=0.032),"wavelet-LHH_firstorder_Skewness"(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95%CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95%CI 0.817-0.997) according to ROC curve analysis. Conclusions: Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.

[Analysis of factors associated with proximal junctional kyphosis after surgery for Lenke type 5 adolescent idiopathic scoliosis].

Objective: To investigate the risk factors associated with the development of proximal junctional kyphosis (PJK) after posterior spinal fusion for in children with Lenke type 5 adolescent idiopathic scoliosis (AIS). Methods: It was a retrospective case-control study that included medical records of 98 children with Lenke type 5 AIS who underwent posterior orthopedic surgery under general anesthesia at the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2013 to December 2018. There were 23 males and 75 females with a mean age of (14.5±2.2) years (10-18 years). Patients were divided into PJK and non-PJK groups according to whether the posterior junctional angle (PJA) was greater than 10° and increased for more than 10° from the preoperative period at the the last follow-up. Univariate analysis was used to analyze the correlation of general data of the children with occurrence of PJK after the operation. Multivariate logistic regression analysis was used to analyze the risk factors of postoperative PJK. Results: There were 35 cases in the PJK group and 63 cases in the non-PJK group. The PJK and non-PJK groups were followed up for (35.6±7.3) months and (36.4±7.5) months, respectively, and the difference was not statistically significant (P=0.637). There was no statistically significant difference between the two groups in general data such as gender, age, and body mass index (all P>0.05), while there were statistically significant differences between the two groups in upper instrumented vertebrea (UIV) location and junctional area posterior ligamentous complex (PLC) injury (all P<0.05). The results of univariate analysis showed that UIV location at T10-T12, junctional area PLC injury, preoperative coronal thoracic curve (TC), preoperative and final follow-up PJA, and preoperative and final follow-up pelvic incidence-lumbarlordosis (PI-LL) were correlated with postoperative PJK (OR=2.50, 5.37, 0.92, 1.12, 1.32, 1.06, 3.35, all P<0.05). Multifactorial logistic regression analysis showed that UIV located at T10-T12 (OR=2.346, 95%CI: 1.582-3.481, P=0.001), junctional area PLC injury (OR=5.112, 95%CI: 1.283-20.418, P=0.023) and last follow-up PI-LL (OR=1.826, 95%CI: 1.558-24.745, P=0.012) were risk factors for the occurrence of postoperative PJK in children with Lenke type 5 AIS. Conclusions: Postoperative UIV fixation to the thoracolumbar segment, PLC injury in the junctional area and excessive postoperative PI-LL in children with Lenke type 5 AIS may be the risk factors for the occurrence of PJK after the operation. It is suggested that avoidance of UIV selection to the thoracolumbar segment, intraoperative protection of the PLC located near the UIV and restoration of a good PI-LL relationship may reduce the incidence of PJK.

[Value of direct immunohistochemical staining in assisting intraoperative frozen diagnosis of bronchiolar adenoma].

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

[Splicing abnormalities caused by a novel mutation in the PHKA2 gene in children with glycogen storage disease type IX].

Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.

[A preliminary report of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis to prevent parastomal hernia].

Objective: To examine the preliminary effect of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis for the prevention of parastomal hernia after abdominoperineal resection for rectal cancer. Methods: This study is a prospective case series study. From June 2021 to June 2022, patients with low rectal cancer underwent laparoscopic abdominoperineal resection combined with extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis at the First Department of General Surgery, Shaanxi Provincial People's Hospital were enrolled. The clinical data and postoperative CT images of patients were collected to analyze the incidence of surgical complication and parastomal hernia. Results: Totally 6 cases of patient were enrolled, including 3 males and 3 females, aging 72.5 (19.5) years (M(IQR)) (range: 55 to 79 years). The operation time was 250 (48) minutes (range: 190 to 275 minutes), the stoma operation time was 27.5 (10.7) minutes (range: 21 to 37 minutes), the bleeding volume was 30 (35) ml (range: 15 to 80 ml). All patients were cured and discharged without surgery-related complications. The follow-up time was 136 (105) days (range: 98 to 279 days). After physical examination and abdominal CT follow-up, no parastomal hernia occurred in the 6 patients up to this article. Conclusions: A method of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis is established. Permanent stoma can be completed with this method safely. It may have a preventive effect on the occurrence of parastomal hernia, which is worthy of further study.

[Analysis on the scrap situation of COVID-19 vaccine in Suzhou city].

To analyze the usage and loss of the COVID-19 vaccine in ten districts of Suzhou city from December 18, 2020 to April 30, 2021.The results showed the loss rate was 0.222‰ in Suzhou city. The loss rate of pre-filled packaging COVID-19 vaccine was higher than that of vial packaging. The loss rate of 40 packaging was the lowest in vial packaging. The loss rate of all kinds of COVID-19 vaccine in stable inoculation unit was the lowest. It is recommended to distribute 40 vial packaging COVID-19 vaccine for centralized vaccination to reduce the loss of COVID-19 vaccine.

Three-Dimensional Dirac Phonons with Inversion Symmetry.

Dirac semimetals associated with bulk Dirac fermions are well known in topological electronic systems. In sharp contrast, three-dimensional (3D) Dirac phonons in crystalline solids are still unavailable. Here we perform symmetry arguments and first-principles calculations to systematically investigate 3D Dirac phonons in all space groups with inversion symmetry. The results show that there are two categories of 3D Dirac phonons depending on their protection mechanisms and positions in momentum space. The first category originates from the four-dimensional irreducible representations at the high symmetry points. The second category arises from the phonon branch inversion, and the symmetry guarantees Dirac points to be located along the high symmetry lines. Furthermore, we reveal that nonsymmorphic symmetries and the combination of inversion and time-reversal symmetries play essential roles in the emergence of 3D Dirac phonons. Our work not only offers a comprehensive understanding of 3D Dirac phonons but also provides significant guidance for exploring Dirac bosons in both phononic and photonic systems.

[Characteristics of PD-L1 expression in tumor cells and tumor microenvironment of DLBCL with MYD88 L265P mutation].

Objective: To study the effect of MYD88 L265P mutation on the expression of PD-L1 in tumor cells and tumor microenvironment in diffuse large B-cell lymphoma (DLBCL), and to provide theoretical basis for immunotherapy for patients. Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to detect the frequency of MYD88 L265P mutation in 72 cases of DLBCL diagnosed by pathologists in Cancer Hospital of Chinese Academy of Medical Sciences from August 2008 to May 2010. Expression of PD-L1 in tumor cells and tumor microenvironment in all samples was evaluated using PD-L1 (22C3) and PD-L1 (SP142) with Ventana automatic immunohistochemical (IHC) platform. The relationship between MYD88 L265P mutation and the expression of PD-L1 in DLBCL tumor cells and tumor microenvironment was assessed. Results: Of the 72 cases of DLBCL, MYD88 L265P mutation was detected in 15 (20.8%) cases. Nine cases with JAK2 amplification were excluded, and the remaining 63 cases of DLBCL were divided into MYD88 L265P mutant group (n=14) and MYD88 L265P wild-type group (n=49). IHC results showed that among the 14 cases of MYD88 L265P mutant groups, PD-L1 (22C3) was positive in 7 cases (7/14) of tumor cells and PD-L1 (SP142) was positive in 4 cases (4/14) of tumor microenvironment. Among the 49 cases of MYD88 L265P wild-type group, 9 cases (18.4%) were positive for PD-L1 (22C3) in tumor cells, and 38 cases (77.6%) were positive for PD-L1(SP142) in tumor microenvironment. In addition, among the 16 cases with PD-L1(22C3) expression in tumor cells, only 2 of the 7 cases with MYD88 L265P mutation were positive for PD-L1 (SP142) in tumor microenvironment. All 9 cases with wild-type MYD88 L265P were positive for PD-L1 (SP142) in tumor microenvironment. Statistical analysis showed that the expression level of PD-L1 (22C3) in tumor cells in the MYD88 L265P mutant group was significantly higher than that in the MYD88 L265P wild-type group (P=0.017). The expression level of PD-L1 (SP142) in tumor microenvironment in the MYD88 L265P mutant group was significantly lower than that in the MYD88 L265P wild-type group (P=0.001). Conclusions: MYD88 L265P mutation may play an important role in the regulation of PD-L1 expression in DLBCL tumor cells and tumor microenvironment. Further studies will provide a theoretical basis for immunotherapy of DLBCL patients with MYD88 L265P mutation.

[A retrospective investigation of new cases of pneumoconiosis from 1958 to 2018 in Guangzhou City].

Objective: To describe the characteristics and the survival status of pneumoconiosis cases reported in Guangzhou City from 1958 to 2018, and to investigate the epidemiological trends of pneumoconiosis. This study is aiming to provide basic data for formulating the guidelines and policies for control of pneumoconiosis, and for evaluating the control effects of pneumoconiosis. Methods: From July 2019 to January 2020, based on the data collected in the pneumoconiosis case cards and database as well as the retrospective follow-up investigate of pneumoconiosis cases, we conducted a descriptive analysis for all the new cases of pneumoconiosis reported from 1958 to 2018 in Guangzhou City. The statistical indices included the number of new pneumoconiosis cases in each decade, types of pneumoconiosis, regional and industrial distributions, survival status, and the change tendency of the diagnosis age and the dust exposure time of pneumoconiosis cases. Results: From 1958 to 2018, a total of 1194 new cases of pneumoconiosis were reported in Guangzhou City, including 1147 males (96.1%) and 47 females (3.9%) . Silicosis (60.1%, 718/1194) and welder's pneumoconiosis (21.5%, 257/1194) were the main types of pneumoconiosis. The top three districts for reporting new cases were Huangpu District (29.0%, 346/1194) , Nansha District (12.6%, 151/1194) and Baiyun District (11.1%, 132/1194) , respectively. The top three industries for reporting new cases were civil engineering construction industry (25.0%, 298/1194) , railway ship aerospace and other transportation equipment manufacturing industry (16.1%, 192/1194) and non-metal mining industry (15.7%, 187/1194) . The diagnosis age for new cases was 47.8 (23.6-79.1) years old, and the dust exposure time was 12.3 (0.4-49.1) years. Both of these two statistical indicators rose first and fell later from 1958 to 2018. As of December 31, 2019, a total of 963 new cases of pneumoconiosis were followed up, of which 467 (48.5%) survived, mainly silicosis (41.3%, 193/467) and welder's pneumoconiosis (43.3%, 203/467) . 496 cases (51.5%) died, and the age of death was 69.9 (32.4-96.9) years old. Conclusion: According to the epidemiological characteristics of pneumoconiosis in Guangzhou, we should focus on key districts and industries in the prevention and control of pneumoconiosis. Besides, the staffs in the occupational disease diagnosis institutions should try the best to collect the complete dust exposure data of new cases of pneumoconiosis. Moreover, the health administrative departments should pay more attention to the management of pneumoconiosis death case reports.

[Analysis of influencing factors of pneumoconiosis complicated with pulmonary tuberculosis].

Objective: To investigate the influencing factors of pneumoconiosis complicated with tuberculosis in order to provide the scientific evidence for formulating the preventive strategies. Methods: From July 2019 to January 2020, all occupational pneumoconiosis patients reported in Guangzhou from 1958 to 2018 were investigated retrospectively (n=1155) . The basic data (including gender, diagnosis time, diagnosis age, dust exposure duration, period, pneumoconiosis disease type, work type and industry) were obtained from pneumoconiosis case card and network report database. The data of pulmonary tuberculosis were collected from the occupational disease diagnosis files of Guangzhou Occupational Disease Prevention and Control Hospital, and were supplemented by telephone follow-up. The distribution of pneumoconiosis and tuberculosis in Guangzhou was analyzed. Binary logistic regression analysis model was used to analyze the influencing factors of pneumoconiosis complicated with pulmonary tuberculosis. Results: Among the 1155 new cases of pneumoconiosis, 357 cases were pneumoconiosis tuberculosis, and the complication rate of tuberculosis was 30.9%. Year of diagnosis, age of diagnosis, dust exposure duration, pneumoconiosis caused by mineral dust and construction industry were influencing factors for pneumoconiosis complicated with pulmonary tuberculosis (OR=0.948, 1.048, 0.972, 3.112, 2.815, P<0.05) . After the adjustment of gender, diagnosis year, diagnosis age, dust exposure duration and diagnosis period, the risk of pulmonary tuberculosis in rock drilling workers was 1.462 times higher than that in other types of work (P<0.05) . Conclusion: The complication rate of tuberculosis in patients with pneumoconiosis is relatively high. The main influencing factors are the year of diagnosis, age of diagnosis, dust exposure duration, the type of pneumoconiosis and the industry. The importance of occupational health examination and health education on prevention and treatment of tuberculosis should be emphasized among dust-exposed workers and pneumoconiosis patients. People with susceptibility factors are the top priority.

Two-Dimensional Dirac Semimetals without Inversion Symmetry.

Realizing stable two-dimensional (2D) Dirac points against spin-orbit coupling (SOC) has attracted much attention because it provides a platform to study the unique transport properties. In previous work, Young and Kane [Phys. Rev. Lett. 115, 126803 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.126803 proposed stable 2D Dirac points with SOC, in which the Berry curvature and edge states vanish due to the coexistence of inversion and time-reversal symmetries. Herein, using the tight-binding model and k·p effective Hamiltonian, we present that 2D Dirac points can survive in the presence of SOC without inversion symmetry. Such 2D Dirac semimetals possess nonzero Berry curvature near the crossing nodes, and two edge states are terminated at one pair of Dirac points. In addition, according to symmetry arguments and high-throughput first-principles calculations, we identify a family of ideal 2D Dirac semimetals, which has nonzero Berry curvature in the vicinity of Dirac points and visible edge states, thus facilitating the experimental observations. Our work shows that 2D Dirac points can emerge without inversion symmetry, which not only enriches the classification of 2D topological semimetals but also provides a promising avenue to observe exotic transport phenomena beyond graphene, e.g., nonlinear Hall effect.

Symmetry-Protected Topological Triangular Weyl Complex.

Weyl points are often believed to appear in pairs with opposite chirality. In this work, we show by first-principles calculations and symmetry analysis that single Weyl phonons with linear dispersion and double Weyl phonons with quadratic dispersion are simultaneously present between two specific phonon branches in realistic materials with trigonal or hexagonal lattices. These phonon Weyl points are guaranteed to locate at high-symmetry points due to the screw rotational symmetry, forming a unique triangular Weyl complex. In sharp contrast to conventional Weyl systems with surface arcs terminated at the projections of a pair of Weyl points with opposite chirality, the phonon surface arcs of the unconventional triangular Weyl complex connect the projections of one double Weyl point and two single Weyl points. Importantly, the phonon surface arcs originating from the triangular Weyl complex are extremely long and span the entire surface Brillouin zone. Furthermore, there are only nontrivial phonon surface states across the isofrequency surface, which facilitates their detection in experiments and further applications. Our work not only offers the promising triangular phonon Weyl complex but also provides guidance for exploring triangular Weyl bosons in both phononic and photonic systems.