Retracted: Low-expressed GAS5 injure myocardial cells and progression of chronic heart failure via regulation of miR-223-3P.

Chronic heart failure (CHF) is a common disease in clinical practice, and its incidence has been increasing in recent years. Understanding the pathogenesis of CHF is the key to its future clinical diagnosis and treatment. Molecular research is a hot topic in modern hospitals, and long non-coding RNA (LncRNA) has been gradually understood and applied in many diseases. The situation of LncRNA GAS5 in CHF is still unclear, so this experiment will investigate the situation of GAS5 in CHF and its effect on myocardial cells, aiming to gain a preliminary understanding of the mechanism of GAS5's effect on CHF. In this study, the expression of GAS5 and miR-223-3p in peripheral blood of CHF patients and healthy subjects was first detected, GAS5 was low in CHF while miR-223-3p was high (P < 0.05). Subsequently, ROC curve analysis showed that GAS5 and miR-223-3p had good predictive value for the occurrence and recurrence of CHF. Secondly, through in vitro experiments, we found that inhibition of GAS5 with elevated expression of miR-223-3p decreased the proliferative capacity of cardiomyocytes and increased apoptotic capacity and inflammatory factors (P < 0.050). Through dual luciferase reporter and RNA immunoprecipitation experiment, we found that miR-223-3p was regulated by GAS5 in a targeted manner.

A fusion antitumor peptide regulates proliferation and apoptosis of endothelial cells.

The present research has been carried out to elicit the mechanism of antiangiogenic activity of a fusion peptide P2. Peptide P2 was designed by the connection of a heptapeptide MMP inhibitor to ES-2, a fragment of Endostatin. In a previous study, P2 demonstrated strong antiangiogenic and antitumor effect, and the current work explains the antiangiogenic mechanism of P2 through endothelial cell proliferation and apoptosis. In our study, it was shown that P2 inhibited HUVECs proliferation at a low serum concentration and this effect might be achieved through arresting cell cycle by decreasing the expression level of Cyclin D1. In addition, P2 was found to induce apoptosis of HUVECs. Using Western blot, it was indicated that P2 induced the cleavage of Caspase-3, the hallmark protease of apoptosis. The activation and expression of the upstream regulator Caspase-9 can also be affected by P2 treatment. Furthermore, P2 reduced the protein level of antiangiogenic factors Bcl-xL and Bcl-2. These results revealed that P2 regulates endothelial cell apoptosis through intrinsic apoptotic pathway.

SENP1 regulates cell migration and invasion in neuroblastoma.

Neuroblastoma (NB) is an embryonic solid tumor derived from precursor cells of the sympathetic nervous system, and accounts for 11% of childhood cancers and around 15% of cancer deaths in children. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in diverse cancers. However, nothing is known about the role of SENPs in NBL. In the present study, we found that SENP1 expression was significantly high in metastatic NB tissues compared with primary NB tissues. Overexpression of SENP1 promoted NB cells migration and invasion. Inhibition of SENP1 could significantly suppress NB cell migration and invasion. Moreover, we found that SENP1 could regulate the expression of CDH1, MMP9, and MMP2. In summary, the data presented here indicate a significant role of SENP1 in the regulation of cell migration and invasion in NB and suppress SENP1 expression as promising candidates for novel treatment strategies of NB.

Predictive Factors for the Spontaneous Recanalization of Large and Middle Cerebral Arteries after Acute Occlusion.

OBJECTIVE: This study aims to investigate the predictive factors for the spontaneous recanalization of occluded arteries in patients with acute ischemic stroke. METHODS: A total of 139 patients with consecutive acute ischemic stroke were enrolled from June 2010 to June 2013. The clinical and biochemical parameters were measured in each participant. Occlusion and recanalization of the carotid artery, the middle cerebral artery, and the vertebral and basilar arteries were identified by using computed tomographic angiography or digital subtraction angiography. RESULTS: Among the 139 patients, 23 showed spontaneous recanalization, whereas 116 did not. In the patients with spontaneous recanalization, the proportion of atrial fibrillation was significantly lower (0% versus 29.31%, P= .01), whereas the proportion of stage 3 hypertension was significantly higher (60.87% versus 32.76%, P= .01) than that of those without recanalization. Logistic regression analysis showed that the proportion of atrial fibrillation was negatively (odds ratio [OR]: .117, 95% confidence interval [CI]: .015-.918, P= .04) associated with spontaneous recanalization, whereas the proportion of stage 3 hypertension was positively (OR: 4.316, 95% CI: 1.533-12.154, P= .01) associated with it. CONCLUSIONS: Atrial fibrillation is associated with reduced spontaneous recanalization of the large and middle cerebral arteries in patients after acute ischemic stroke-induced occlusion, whereas stage 3 hypertension may contribute to the promotion of the recanalization.

Severe anemia and melena caused by pyeloduodenal fistula due to renal stone-associated squamous cell carcinoma.

Pyeloduodenal fistula is a rare condition and its association with malignancy is even rarer. Herein we report the case of a 66-year-old man who was admitted to the hospital with a three-month history of intermittent melena and a more than 20-year history of right-side renal stones. Computed tomography showed a heterogeneous right renal mass with a staghorn stone that had invaded the duodenum and caused an internal fistula. An upper gastrointestinal series showed pyeloduodenal fistula. The patient underwent an exploratory operation and a biopsy was taken at the peripelvic region. Pathological examination verified the existence of squamous cell carcinoma. To our knowledge, this is the first case of pyeloduodenal fistula associated with renal stones, squamous cell carcinoma and upper urinary tract calculus presenting on melena. We report on the features of this rare entity but also review and summarize the etiology, diagnosis and treatment options that can be extrapolated from the existing literature.

Generation, functional analysis and utility of Citrus grandis EST from a flower-derived cDNA library.

Pummelo (Citrus grandis) is one of the most important species found in the genus Citrus and one of the ancestors of sweet oranges. We used flower buds at different developmental stages to construct the first cDNA library for this species. A total of 3,758 EST sequences were generated from the cDNA library and clustered into 2,228 unigenes, comprising 451 contigs and 1,777 singletons. Among these unigene sequences, 1,266 have significant homology to the non-redundant protein database, from which 891 were assigned to one or more gene ontology categories. Functional categorization of the annotated unigenes showed that 760 genes were involved in molecular function, 1,189 in biological processes and 1,154 in cellular component categorization. Homologs of genes regulating many aspects of flower development were also identified, including those for organ development, cell-cycle control and cell and tissue differentiation. The majority of these genes (e.g., embryo relatives, YABBY-like, MAD Box, SKP-like and SRNAs) are the first representatives in Citrus, providing an opportunity to explore the cause of self incompatibility and embryo development in Citrus. Patterns of transcript accumulation were characterized by real-time qPCR for 13 of these genes. Many potential molecular markers were also identified in this EST data set; 212 Simple Sequences Repeats (SSRs), 717 transposon elements and 115 candidate single nucleotide polymorphisms (SNPs) were found. An assessment of a set of 212 SSR primer pairs on 16 citrus genotypes showed polymorphism with 122 (57.82%) markers. Similarly, a set of eight contigs were used to confirm in silico predicated SNPs in a set of five genotypes using wet lab experiments, three contigs were generated as scorable and sequenceable amplicons and no PCR amplicons were obtained from five contigs. The outcome of this study could aid in the discovery of genes involved in reproductive developments. Identified candidate genes can be experimentally tested for their functions in various important processes. SSR, SNP and transposon element-containing data sets may facilitate marker development and can be used for citrus molecular breeding, linkage map construction, evolutionary, phylogenetic and population genetic studies.

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation.Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1ß Interleukin-1ß, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4',6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen.

Evaluation of different multidimensional LC-MS/MS pipelines for isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of potato tubers in response to cold storage.

Cold-induced sweetening in potato tubers is a costly problem for the food industry. To systematically identify the proteins associated with this process, we employed a comparative proteomics approach using isobaric, stable isotope coded labels to compare the proteomes of potato tubers after 0 and 5 months of storage at 5 °C. We evaluated both high pH reverse phase (hpRP) liquid chromatography (LC) and off-gel electrophoresis (OGE) as first dimension fractionation methods followed by nanoLC-MS/MS, using two high performance mass spectrometry platforms (Q-TOF and Orbitrap). We found that hpRP-LC consistently offered better resolution, reduced expression ratio compression, and a more MS-compatible workflow than OGE and consistently yielded more unique peptide/protein identifications and higher sequence coverage with better quantification. In this study, a total of 4463 potato proteins were identified, of which 46 showed differential expressions during potato tuber cold storage. Several key proteins important in controlling starch-sugar conversion, which leads to cold-induced sweetening, as well as other proteins that are potentially involved in this process, were identified. Our results suggest that the hpRP-RP shotgun approach is a feasible and practical workflow for discovering potential protein candidates in plant proteomic analysis.

A PD-1 peptide antagonist exhibits potent anti-tumor and immune regulatory activity.

Antibodies blocking the PD-1/PD-L1 pathway have achieved great success. However, some disadvantages of antibodies have been found, which limit their clinical applications. Peptide antagonists are alternatives to antibodies in PD-1/PD-L1 blockage, but successful studies in this area are limited. A PD-1 targeting peptide, P-F4, was identified using phage display. P-F4 bound PD-1 with an affinity of 0.119 µM, inhibited PD-1/PD-L1 interaction at the cellular level and modulated T cell activity in vitro. We have overcome the poor solubility and rapid degradation problems of this peptide by packaging P-F4 in nanoparticles. In vivo experiments demonstrated that P-F4 nanoparticles could strongly inhibit tumor growth in a CT26 mouse model. Further research revealed that treatment of P-F4 nanoparticles increased CD8+T cells and reduced Tregs in the tumor microenvironment and tumor-draining lymph nodes. It was shown that treatment of P-F4 nanoparticles also increased lymphocytic activities, including proliferation, cytokine secretion and cytolytic activity. Moreover, computer modeling suggested that the P-F4 binding site to PD-1 overlaps with the PD-L1 binding surface. In this study, a peptide candidate for cancer immunotherapy was provided, and its working mechanisms were studied.

Clinical analysis of intestinal fistula associated with invasive intervention for acute pancreatitis / 中华胰腺病杂志

Objective:To analyze the clinical characteristics of invasive intervention-related intestinal fistula in patients with acute pancreatitis (AP).Methods:We retrospectively analyzed the clinical data of 177 moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) patients who received invasive intervention in Peking Union Medical College Hospital from January 2003 to December 2022. Patients were divided into fistula group and non-fistula group based on the presence or absence of fistula after or during receiving invasive interventions. The age, gender, etiology, systemic inflammatory response syndrome(SIRS), impairment of organ function, revised Atlanta classification, bedside index of severity of acute pancreatitis(BISAP), Balthazar CT classification, extra-pancreatic involvement and secondary infection of local complications, indications, timing and modalities of invasive interventions, length of hospitalization, length of intensive care and outcomes were recorded. The differences on clinical characteristics were compared between the two groups.Results:Intestinal fistulae were found in 21(11.9%) cases during or after invasive intervention, including 8 during or after percutaneous drainage and 13 during or after surgeries. 51 cases received endoscopic drainage or debridement and no intestinal fistula occurred after endoscopic management. Compared to patients without fistula, the median age was younger in the fistula group (36 vs 45 years, P=0.014), and the occurrence of SIRS (95.2% vs 59.6%, P=0.001), extra-pancreatic invasion (100.0% vs 67.3%, P=0.002), and secondary infection (71.4% vs 36.5%, P=0.002) were higher. Patients with fistula had a longer median length of hospitalization (71 vs 40 days, P=0.016) and intensive care (8 vs 0 days, P=0.002). All patients in the fistula group had peri-pancreatic, abdominal and retroperitoneal involvement seen on imaging or intraoperatively. The intestinal fistulae mainly occurred in the colon ( n=13, 61.9%) and the duodenum ( n=6, 28.6%). The confirmed diagnosis of fistulae was based on transfistula imaging ( n=11) or digestive tract imaging ( n=5). Among 13 cases with colonic fistulae, nonsurgical treatment was preferred in 9 cases, and surgeries of fistula repairmen or proximal ostomy were preferred in 4 cases. Among 8 cases with non-colonic fistulae, nonsurgical treatment was preferred in 7 cases, and only 1 case repaired the fistula immediately during the intraoperative detection. Conclusions:Intestinal fistula is an important complication of severe AP, and it is closely associated with invasive interventions. Improved invasive intervention strategies may help prevent intestinal fistula formation; timely and effective management of intestinal fistula may help avoid complications and shorten hospitalization.

Analysis of the incidence and mortality of thyroid cancer in Shandong Province from 2012 to 2022 based on the age-period-cohort model / 中华预防医学杂志

Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.

Analysis of the incidence and mortality of thyroid cancer in Shandong Province from 2012 to 2022 based on the age-period-cohort model / 中华预防医学杂志

Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.

Epidemiological characteristics and clinical features of pertussis in Shandong Province from 2007 to 2022 / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and clinical features of pertussis cases reported in Shandong Province of China. Methods: Data on pertussis cases in Shandong Province from 2007 to 2022 were collected from China Information System for Disease Control and Prevention. At the same time, some case information was collected from the database of notifiable pertussis in Shandong Province from 2007 to 2022. The distribution characteristics and clinical features of pertussis were analyzed. A spatial distribution map of pertussis cases in Shandong Province was drawn. Results: A total of 26 122 pertussis cases were reported in Shandong Province during 2007-2022, with an annual incidence rate ranging from 0.11 to 5.77 cases per 100 000 people. Cases occurred throughout the whole year, with a seasonal peak occurring in spring and summer, especially in July and August. In recent years, reported cases were mainly distributed in the central and western regions of Shandong Province, with fewer cases in the eastern region. The hot spots of the disease shifted from Heze and Dezhou City in 2007-2013 to Jinan and Tai'an city in 2014-2022. The age range of onset was from 1 day to 93 years old. The proportion of cases with age≤1 year was the largest (41.81%, 10 922/26 122), and the proportion of cases aged 0-6 months decreased from 32.21% (67/208)-55.67% (157/282) within the period of 2007 to 2013 to 16.78% (883/5 263)-41.97% (444/1 058) within the period of 2014 to 2022, with a statistically significant trend (χ² trend=670.01, P<0.001). There were 13 682 male cases and 12 440 female cases, with a male-female ratio of 1.10∶1. The male-female ratio was 1.45∶1 (806∶556) from 2007 to 2013 and 1.08∶1 (12 876∶11 884) from 2014 to 2022. The proportion of women increased from 42.31% (88/208) in 2007 to 47.84% (2 518/5 263) in 2022, and with a significant trend (χ² trend=22.25, P<0.001). In pertussis cases, the proportions of scattered children, kindergarten children and students were 71.38% (18 645/26 122), 15.13% (3 951/26 122), and 11.60% (3 031/26 122), respectively. The top five clinical symptoms of pertussis cases were paroxysmal spasmodic cough (86.33%, 21 411 cases), flushing (39.61%, 9 824 cases), restless sleep (34.51%, 8 558 cases), fever (30.80%, 7 638 cases), and crowing (27.53%, 6 829 cases). Among 24 802 cases, there were 15 542 cases (62.66%) with a history of immunization against pertussis vaccine. Conclusion: From 2007 to 2022, the incidence rate of pertussis cases in Shandong Province shows an upward trend, with the majority being young children, and the clinical symptoms are relatively typical.

Analysis of the complete genome characterization of 11 human astrovirus strains in Shandong Province / 中华预防医学杂志

Objective: To study the complete genome characterization of Human Astrovirus (HAstV) in Shandong Province. Methods: Stool samples from acute flaccid paralysis (AFP) surveillance in Shandong Province from 2020 to 2022 were collected, and HAstV nucleic acid was examined by real-time quantitative PCR (qPCR). Next-generation sequencing (NGS) was conducted for the positive samples to obtain complete genome sequences and identify the genotype. Homology comparison and phylogenetic analysis were performed by using BioEdit and Mega software. Results: A total of 667 samples were examined by qPCR, of which 14 were HAstV-positive (2.1%), including HAstV-1 (n=6), MLB1 (n=6), MLB2 (n=1), and VA2 (n=1). The complete genome sequences were obtained from 11 samples. The six HAstV-1 sequences of this study had 98.2% to 99.9% nt similarities with each other and 87.6% to 98.6% with those from other regions. The four MLB1 sequences of this study had 99.1% to 99.9% nt similarities with each other and 92.2% to 99.4% with those from other regions. The VA2 sequence of this study had 96.0% to 96.3% nt similarities with those from other regions. Phylogenetic analysis based on ORF2 region showed that the local HAstV-1 sequences were most closely related to Japanese strains, and had distinct topology with phylogenies based on ORF1a and ORF1b regions. Conclusion: The complete genome sequences of 11 HAstV strains are obtained, and the VA2 complete genome is found.

Clinical characteristics analysis of primary pancreatic lymphoma / 中华胰腺病杂志

Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

Epidemiological characteristics and clinical features of pertussis in Shandong Province from 2007 to 2022 / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and clinical features of pertussis cases reported in Shandong Province of China. Methods: Data on pertussis cases in Shandong Province from 2007 to 2022 were collected from China Information System for Disease Control and Prevention. At the same time, some case information was collected from the database of notifiable pertussis in Shandong Province from 2007 to 2022. The distribution characteristics and clinical features of pertussis were analyzed. A spatial distribution map of pertussis cases in Shandong Province was drawn. Results: A total of 26 122 pertussis cases were reported in Shandong Province during 2007-2022, with an annual incidence rate ranging from 0.11 to 5.77 cases per 100 000 people. Cases occurred throughout the whole year, with a seasonal peak occurring in spring and summer, especially in July and August. In recent years, reported cases were mainly distributed in the central and western regions of Shandong Province, with fewer cases in the eastern region. The hot spots of the disease shifted from Heze and Dezhou City in 2007-2013 to Jinan and Tai'an city in 2014-2022. The age range of onset was from 1 day to 93 years old. The proportion of cases with age≤1 year was the largest (41.81%, 10 922/26 122), and the proportion of cases aged 0-6 months decreased from 32.21% (67/208)-55.67% (157/282) within the period of 2007 to 2013 to 16.78% (883/5 263)-41.97% (444/1 058) within the period of 2014 to 2022, with a statistically significant trend (χ² trend=670.01, P<0.001). There were 13 682 male cases and 12 440 female cases, with a male-female ratio of 1.10∶1. The male-female ratio was 1.45∶1 (806∶556) from 2007 to 2013 and 1.08∶1 (12 876∶11 884) from 2014 to 2022. The proportion of women increased from 42.31% (88/208) in 2007 to 47.84% (2 518/5 263) in 2022, and with a significant trend (χ² trend=22.25, P<0.001). In pertussis cases, the proportions of scattered children, kindergarten children and students were 71.38% (18 645/26 122), 15.13% (3 951/26 122), and 11.60% (3 031/26 122), respectively. The top five clinical symptoms of pertussis cases were paroxysmal spasmodic cough (86.33%, 21 411 cases), flushing (39.61%, 9 824 cases), restless sleep (34.51%, 8 558 cases), fever (30.80%, 7 638 cases), and crowing (27.53%, 6 829 cases). Among 24 802 cases, there were 15 542 cases (62.66%) with a history of immunization against pertussis vaccine. Conclusion: From 2007 to 2022, the incidence rate of pertussis cases in Shandong Province shows an upward trend, with the majority being young children, and the clinical symptoms are relatively typical.

Analysis of the complete genome characterization of 11 human astrovirus strains in Shandong Province / 中华预防医学杂志

Objective: To study the complete genome characterization of Human Astrovirus (HAstV) in Shandong Province. Methods: Stool samples from acute flaccid paralysis (AFP) surveillance in Shandong Province from 2020 to 2022 were collected, and HAstV nucleic acid was examined by real-time quantitative PCR (qPCR). Next-generation sequencing (NGS) was conducted for the positive samples to obtain complete genome sequences and identify the genotype. Homology comparison and phylogenetic analysis were performed by using BioEdit and Mega software. Results: A total of 667 samples were examined by qPCR, of which 14 were HAstV-positive (2.1%), including HAstV-1 (n=6), MLB1 (n=6), MLB2 (n=1), and VA2 (n=1). The complete genome sequences were obtained from 11 samples. The six HAstV-1 sequences of this study had 98.2% to 99.9% nt similarities with each other and 87.6% to 98.6% with those from other regions. The four MLB1 sequences of this study had 99.1% to 99.9% nt similarities with each other and 92.2% to 99.4% with those from other regions. The VA2 sequence of this study had 96.0% to 96.3% nt similarities with those from other regions. Phylogenetic analysis based on ORF2 region showed that the local HAstV-1 sequences were most closely related to Japanese strains, and had distinct topology with phylogenies based on ORF1a and ORF1b regions. Conclusion: The complete genome sequences of 11 HAstV strains are obtained, and the VA2 complete genome is found.

COVID-19-mediated pulmonary fibrosis: from mechanisms to medicines / 中国药理学通报

Coronavirus disease-19 (COVID-19), a global epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to lung injury in millions of people. SARS-CoV-2 can not only cause cytokine storm, acute respiratory distress syndrome and respiratory failure in the phase of acute infection, but also have potential long-term effects on the lungs. Survivors of severe COVID-19 may develop pulmonary fibrosis, resulting in permanent lung injury. In this review we expound the occurrence and development of COVID-19-related pulmonary fibrosis, summarize the key roles of TGF-p/Smad, TGF-fV MAPK, JAK/STAT, Wnt/(3-catenin, YAP/TAZ, NF-KB and PI3K/Akt signal pathways in this process, and analyze the advantages and disadvantages of antiviral drugs, anti-fibrosis drugs, cytokine-targeted drugs, corticosteroids, spironolactone, traditional Chinese medicine prescriptions and lung transplantation in its treatment. This review may provide a reference for the study of pathological mechanism and clinical treatment of COVID-19-re-lated pulmonary fibrosis.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.