Editing approaches to treat Alpha-1 Antitrypsin Deficiency (AATD).

TOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency (AATD) is a genetic disorder most commonly due to a single G to A point mutation, leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly intravenous augmentation therapy and is considered sub-optimal for these patients. Furthermore, there is currently no approved treatment for liver manifestations. The unmet medical need for AATD patients remains high and new treatment options are needed to treat the underlying disease etiology. REVIEW FINDINGS: Advances in genomic medicines may enable treatment by editing the DNA or RNA sequence to produce wild-type AAT instead of the mutated AAT caused by the E342K mutation. One approach can be achieved by directing endogenous Adenosine Deaminases that act on RNA (ADARs) to the E342K RNA site, where they catalyze adenosine to inosine conversion through a process known as RNA editing. The A-I RNA change will be read as a G during protein translation, resulting in an altered amino acid and restoration of wild-type AAT secretion and function. SUMMARY: In this review, we will discuss the pathophysiology of AATD and emerging treatment options with particular focus on RNA editing as a disnd have stock options in ease-modifying treatment for both liver and lung disease.

Interpretation of the 5th edition WHO classification of adrenal cortical tumors / 中华病理学杂志

Non-neoplastic lesions were added in the 5th edition WHO classification of adrenal cortical tumor based on the recent update, including adrenal rests, adrenal cysts, congenital adrenal hyperplasia and adrenocortical nodular disease. A range of tumor concepts were updated or refined based on tumor cell origin, histopathology, oncology and molecular biology. The most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease, which now includes sporadic nodular adrenocortical disease, bilateral micronodular adrenal cortical disease, and bilateral macronodular adrenal cortical disease. The 5th edition WHO classification endorses the nomenclature of the HISTALDO classification to help the classification of aldosterone producing adrenal cortical lesions, which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production. The 5th edition WHO classification does not change the Weiss and Lin-Weiss-Bisceglia histopathologic criteria for diagnosing adrenal cortical carcinomas, and underscores the diagnostic and prognostic impact of angioinvasion in these tumors. Reticulin algorithm and Helsinki scoring system were added to assist the differential diagnosis of adrenal cortical neoplasms in adults. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. The 5th edition WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm2) and Ki-67 labeling index which play an essential role in the dynamic risk stratification of affected patients. This review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies in the 5th edition WHO classification.

Diagnosis and Management of Pseudoguttata: A Literature Review.

Corneal pseudoguttata (PG), also known as pseudoguttae or secondary guttata, is a transient, reversible endothelial edema commonly associated with anterior segment pathology. While considered rare, PG presents on slit-lamp examination more commonly than originally thought. We have clinically observed PG after refractive surgeries, in association with infectious keratitis, and following medication use. PG presents as dark lesions on slit-lamp exam with specular illumination, similar to primary corneal guttata. PG is distinct from guttata because PG resolves over time and does not involve Descemet's membrane. Other ocular findings that may be confused with guttata include endothelial blebs (EB) and endothelial denudation (ED). EB are possibly a type of PG that present after contact lens use or hypoxia. ED is a distinct entity that is characterized by loss of endothelial cells without involvement of Descemet's membrane. Confocal microscopy may be useful in differentiating these four endothelial lesions, with differences in border definition and the presence of hyperreflective areas two main distinctions. PG presents as a hyporeflective, elevated shape without clear borders on confocal microscopy. PG, EB, and ED can resolve with time without the need for surgical intervention, unlike corneal guttata. Treatment of the underlying condition will lead to resolution of both PG and EB.

High dependency unit reduce ICU readmission rate in patients with severe liver disease: A clinical study / 中华肝脏病杂志

Objective: To explore the difference in intensive care unit (ICU) readmission rate between high dependency unit (HDU) and general ward for the patients with severe liver disease (SLD), and reflect the effect of HDU on SLD patientse. Methods: A clinical cohort of patients transferred out of ICU was established, and patients with severe liver disease who were transferred to HDU& general ward from July 2017 to December 2021 in the intensive care Unit of the Fifth Medical Center of PLA General Hospital were continuously enrolled. The main liver function indexes and MELD scores between the two groups were compared. Analyze the differences in severity and ICU readmission rate of SLD patients transferred to different wards, and clarify the role of HDU in the management of SLD patient. Area under the receiver operating characteristic (AUROC) was used to investigate the value of MELD score in predicting the occurrence of return to ICU. Results: The level of INR, TB, ALT and MELD scores of SLD patients transferred to HDU were significantly higher than those of patients transferred to general ward (all P < 0.05). MELD > 17 was found in 70.7% of SLD patients transferred to HDU group, while MELD ≤ 17 was found in 61.9% of SLD patients in general ward group. The ICU readmission rate of all patients in this cohort was 11.4%. By MELD quartile stratification, patients with SLD whose MELD > 23 had a significantly higher ICU readmission rate (20.0%) than those with SLD whose MELD ≤ 23 (8.6%) (P = 0.020). The ICU readmission rate was 8.2% when MELD ≤ 23 in the HDU group and 9.1% when MELD > 23, showing no significant difference (P = 1.000). The ICU readmission rate was 8.8% when MELD ≤ 23 in the general ward group. ICU reentry rate increased significantly to 36.4% when MELD > 23 (P = 0.001). MELD Score predicts that the optimal cut-off value of SLD patients in general ward readmitted to ICU was 23.5. Conclusion: The high dependency unit could better admit patients with SLD who were transferred out of ICU and required step-down treatment, and significantly reduced the ICU readmission rate of patients with SLD who were transferred out of ICU with MELD > 23. The patients with SLD and MELD score > 23 are suitable to be transferred from ICU to HDU.

Molecular detection and phylogenetic analysis of Wolbachia infection in common mosquito species in Henan Province / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the infection and genotypes of Wolbachia in common mosquito species in Henan Province, so as to provide insights into management of mosquito-borne diseases.@*METHODS@#Aedes, Culex and Anopheles samples were collected from cowsheds, sheepfolds and human houses in Puyang, Nanyang City and Xuchang cities of Henan Province from July to September, 2022, and the infection of Wolbachia was detected. The 16S rDNA and wsp genes of Wolbachia were amplified and sequenced. Sequence alignment was performed using the BLAST software, and the obtained 16S rDNA gene sequence was compared with the sequence of the 16S rDNA gene in GenBank database. In addition, the phylogenetic trees were created based on 16S rDNA and wsp gene sequences using the software MEGA 11.0.@*RESULTS@#A total 506 female adult mosquitoes were collected from three sampling sites in Nanyang, Xuchang City and Puyang cities from July to September, 2022. The overall detection of Wolbachia was 45.1% (228/506) in mosquitoes, with a higher detection rate in A. albopictus than in Cx. pipiens pallens [97.9% (143/146) vs. 50.6% (85/168); χ2 = 88.064, P < 0.01]. The detection of Wolbachia in Cx. pipiens pallens was higher in Xuchang City (96.8%, 62/64) than in Nanyang (15.6%, 7/45) and Puyang cities (27.1%, 16/59) (χ2 = 89.950, P < 0.01). The homologies of obtained Wolbachia 16S rDNA and wsp gene sequences were 95.3% to 100.0% and 81.7% to 99.8%. Phylogenetic analysis based on wsp gene sequences showed Wolbachia supergroups A and B in mosquito samples, with wAlbA and wMors strains in supergroup A and wPip and wAlbB strains in supergroup B. Wolbachia strain wAlbB infection was detected in A. albopictus in Puyang and Nanyang Cities, while Wolbachia strain wPip infection was identified in A. albopictus in Xuchang City. Wolbachia strain wAlbA infection was detected in Cx. pipiens pallens sampled from three cities, and one Cx. pipiens pallens was found to be infected with Wolbachia strain wMors in Nanyang City.@*CONCLUSIONS@#Wolbachia infection is commonly prevalent in Ae. albopictus and Cx. pipiens pallens from Henan Province, and Wolbachia strains wAlbB and wAlbA are predominant in Ae. albopictus, while wPip strain is predominant in Cx. pipiens pallens. This is the first report to present Wolbachia wMors strain infection in Cx. pipiens pallens in Henan Province.

Construction of a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin / 中国血吸虫病防治杂志

OBJECTIVE@#To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to provide insights into creation of a sensitive and highly efficient surveillance and early warning system for schistosomiasis.@*METHODS@#National and international publications, documents, laws and regulations pertaining to schistosomiasis control were retrieved with keywords including schistosomiasis, surveillance, early warning and control interventions from 2008 to 2022, and a thematic panel discussion was held to preliminarily construct surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin. The index system was then comprehensively scored and screened using the Delphi method, and the weight of each index was determined using analytic hierarchy process and the modified proportional allocation method. In addition, the credibility of the Delphi method was evaluated using positive coefficient, authority coefficient, degree of concentration and degree of coordination of experts.@*RESULTS@#Following two rounds of expert consultation, a surveillance and early warning index system for schistosomiasis transmission risk in endemic areas along the middle and lower reaches of the Yangtze River basin was preliminarily constructed, including 3 primary indicators, 9 secondary indicators and 41 tertiary indicators. The normalized weights of primary indicators epidemics, natural and social factors and comprehensive control were 0.639 8, 0.145 6 and 0.214 6, respectively, and among all secondary indicators, snail status (0.321 3) and schistosomiasis prevalence (0.318 5) had the highest combined weights, while social factors had the lowest combined weight (0.030 4). Of all tertiary indicators, human egg-positive rate (0.041 9), number of acute schistosomiasis cases (0.041 5), number of stool-positive bovine and sheep (0.041 1), and prevalence of Schistosoma japonicum in free-ranging livestock (0.041 1) had the highest combined weights. During two rounds of consultation, the positive coefficient of experts was both 100%, and the authority coefficient was both 0.9 and greater, while the coordination coefficients were 0.338 to 0.441 and 0.426 to 0.565 (χ2 = 22.875 to 216.524, both P values < 0.05).@*CONCLUSIONS@#The established surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin is of great scientific values and authority, which may provide insights into construction of the sensitive and highly efficient surveillance and early warning system for schistosomiasis in the context of low prevalence and low intensity of infection in China.

Impact of COVID-19 pandemic on the management of imported malaria in China / 中国血吸虫病防治杂志

OBJECTIVE@#To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance.@*METHODS@#All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021).@*RESULTS@#A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ2 = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ2 = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ2 = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ2= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ2 = 3.95, P < 0.05).@*CONCLUSIONS@#The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.

Prevalence of Echinococcus infections in wild carnivores based on copro - DNA tests in Serthar County of Sichuan Province / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the prevalence of Echinococcus infections in wild carnivores in Serthar County, Sichuan Province, so as to provide insights into echinococcosis control in local areas.@*METHODS@#Stool samples were collected from wild carnivores in Serthar County, Sichuan Province in May 2021, and the host sources of stool samples and Echinococcus infections were identified using PCR assays. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was estimated in different hosts.@*RESULTS@#A total of 583 stool samples were collected from wild carnivores, including 147 stool samples from fox, 154 from wolf, 227 from wild dogs and 11 from lynx. The overall prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.68%, 0.19% and 14.20% in canine stool samples, and no E. granulosus infection was detected in fox stool samples, while the prevalence of E. multilocularis and E. shiquicus infections was 0.68% and 47.62% in fox stool samples (χ2 = 88.41, P < 0.001). No E. granulosus or E. shiquicus infection was detected in wolf stool samples, and the prevalence of E. multilocularis infection was 10.39% in wolf stool samples. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.73%, 0.44% and 2.20% in canine stool samples (χ2 = 12.13, P < 0.01). In addition, the prevalence of E. multilocularis infections was significantly higher in wolf stool samples than in canine and fox stool samples (χ2 = 13.23, P < 0.01), and the prevalence of E. shiquicus infections was significantly higher in fox stool samples than in canine and wolf stool samples (χ2 = 187.01, P < 0.001). No Echinococcus infection was identified in 11 lynx stool samples.@*CONCLUSIONS@#The prevalence of Echinococcus infections is high in wild canines in Serthar County, Sichuan Province. Wolf, wild dog and fox all participate in the wild life cycle of E. multilocularis in Serthar County, and wolf and wild dogs may play a more important role.

Malignant peripheral nerve sheath tumor: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

Glomuvenous malformation: a clinicopathological analysis of 31 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.

Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance / 中华病理学杂志

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

Factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery / 中华胃肠外科杂志

Objective: To obtain experience and generate suggestions for reducing average hospital stays, optimizing perioperative management of patients with gastric cancer and improving utilization of medical resources by analyzing the factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery (ERAS). Methods: This was a case-control study. Inclusion criteria: (1) pathologically diagnosed gastric adenocarcinoma; (2) radical surgery for gastric cancer; and (3) complete clinicopathologic data. Exclusion criteria: (1) history of upper abdominal surgery; (2) presence of distant metastasis of gastric cancer or other ongoing neoplastic diseases; (3) concurrent chemoradiotherapy; and (4) preoperative gastric cancer-related complications such as obstruction or perforation. The study cohort comprised 285 eligible patients with hospital stays of ≥30 days (super-long hospital stay group). Using propensity score matching in a 1:1 ratio, age, sex, medical insurance, pTNM stage, and extent of surgical resection as matching factors, 285 patients with hospital stays of < 30 days during the same period were selected as the control group (non-long hospital stay group). The primary endpoint was relationship between pre-, intra-, and post-operative characteristics and super-long hospital stays. Clavien-Dindo grade was used to classify complications. Results: Univariate analysis showed that number of comorbidities, number of preoperative consultations, preoperative consultation, inter-departmental transference, operation time, open surgery, blood loss, intensive care unit time, presence of surgical or non-surgical complications, Clavien-Dindo grade of postoperative complications, and reoperation were associated with super-long hospital stays (all P<0.05). Inter-departmental transference (OR=4.876, 95% CI: 1.500-16.731, P<0.001), preoperative consultation time ≥ 3 d (OR=1.758, 95%CI: 1.036-2.733, P=0.034), postoperative surgery-related complications (OR = 6.618, 95%CI: 2.141-20.459, P=0.01), and higher grade of complications (Clavien-Dindo Grade I: OR = 7.176, 95%CI: 1.785-28.884, P<0.001; Clavien-Dindo Grade II: OR = 18.984, 95%CI: 6.286-57.312, P<0.001; Clavien-Dindo Grade III-IV: OR=7.546, 95%CI:1.495-37.952, P=0.014) were independent risk factors for super-long hospital stays. Conclusion: Optimizing preoperative management, enhancing perioperative management, and surgical quality control can reduce the risk of prolonging average hospital stay.

Application of spatial statistics in studying the distribution of food contamination / 中华流行病学杂志

Objective: Based on data related to arsenic contents in paddy rice, as part of the food safety monitoring programs in 2017, to discuss and explore the application of spatial analysis used for food safety risk assessment. Methods: One province was chosen to study the spatial visualization, spatial point model estimation, and kernel density estimation. Moran's I statistic of spatial autocorrelation methods was used to analyze the spatial distribution at the county level. Results: Data concerning the spatial point model estimation showed that the spatial distribution of pollution appeared relatively dispersive. From the kernel density estimation, we found that the hot spots of pollution were mainly located in the central and eastern regions. The global Moran's I values appeared as 0.11 which presented low spatial aggregation to the rice arsenic contamination and with statistically significant differences. One "high-high" and two typical "low-low" clustering were seen in this study. Conclusion: Results from our study provided good visual demonstration, identification of pollution distribution rules, hot spots and aggregation areas for research on the distribution of food pollutants. Spatial statistics can provide technical support for the implementation of issue-based monitoring programs.

Trend on mortality/incidence ratio of acute myocardial infarction in Tianjin from 2007 to 2015 / 中华流行病学杂志

Objective: To explore the variation for mortality/incidence (MI) ratio on acute myocardial infarction (AMI) in Tianjin from 2007 to 2015. Methods: Data from both disease and death surveillance systems on AMI in Tianjin from 2007 to 2015, were collected. Incidence and mortality for AMI of people over 35 years old were calculated and fitted by using the exponential model. Annual MI ratios by gender and different age groups were calculated. Join-point regression was used for sensitivity analysis of the ratio. Results: Other than 2007, 2010, 2014 and 2015, the ratios in rest of the years were all bigger than one. From 2007 to 2015, the ratios were ranging from 0.80 to 1.60, with 0.90 to 1.80 for females, and 0.80 to 1.40 for males, respectively. Conclusion: The MI ratio on AMI changed relatively stable in Tianjin from 2007 to 2015, but the AMI incidence data in Tianjin seemed underreported, especially for people over 75 years old, indicating that some elderly AMI cases were not reported to the disease surveillance system.

Progress of research on toll-like receptors family gene polymorphism and susceptibility to tuberculosis / 中华流行病学杂志

Tuberculosis is a chronic infectious disease caused by Mycobacterium (M.) tuberculosis. Innate immunity plays an important role in the response to M. tuberculosis. Toll-like receptors (TLRs) are important pattern recognition receptors in innate immunity. TLRs serve as switches that play decisive roles in identifying pathogens-related components. Previous studies found that TLR1, TLR2, TLR4, TLR9 were essential to promote the development of innate immune responses. The SNPs of rs4833095, rs5743618, rs3923647 of TLR1, rs57473708, rs3804099 of TLR2 and rs352139, rs5743836 of TLR9 were closely related to the susceptibility of tuberculosis in some populations. And there appeared certain relationship between the polymorphisms of TLR3, TLR6, TLR7, TLR8, TLR10 and the susceptibility of tuberculosis. The normal function of TLRs ensures the body's normal immune response to M. tuberculosis. The diversity of TLRs genes allows different individuals to respond differently to the same pathogen. Studies targeting on the relationship between single nucleotide polymorphism in TLRs and susceptibility to tuberculosis can predict the susceptibility to tuberculosis in some populations, as well as discover new drugs targets.

Series study on the relationship between air quality index and tuberculosis incidence in Beijing / 中华流行病学杂志

Objective: To analyze the effect of air quality index (AQI) on the incidence of tuberculosis (TB) in Beijing, and to provide evidence for setting up a better program regarding prevention and control of tuberculosis. Methods: Generalized additive model (GAM) was used to analyze the association between AQI and the incidence of tuberculosis in Beijing, from January 1, 2014 to November 9, 2016. Confounding factors as meteorological conditions and time trends were under control. Results: In Beijing, a total of 14 533 TB cases with definite dates of onset were collected during the study period, with 36 children excluded from the study. Finally, 14 497 cases were included in the study, including 9 513 men and 4 984 women, with 11 290 adults (15-59 years old) and 3 207 elderly (≥60 years old). Data from the optimal single-day lag effect of GAM showed that,with every 10 increase of AQI, the percent of increase on the onsets of overall, male, female and adult; tuberculosis cases were 0.85% (95%CI: 0.26%-1.44%), 0.83% (95%CI: 0.24%-1.42%), 0.93% (95%CI: 0.24%-1.62%) and 0.88% (95%CI: 0.29%-1.46%), respectively. The optimal lag time of the single-day effects were 15 days (lag15), but 16 days (lag16) for male. The optimal cumulative lag effect showed that with every 10 AQI increase, the percent of increase on the onsets of overall, male, female and adult tuberculosis cases were 1.92% (95%CI: 0.23%-3.16%), 1.94% (95%CI:0.15%-3.72%), 2.04% (95%CI: 0.10%-3.97%) and 2.00% (95%CI: 0.30%-3.69%), respectively, with the optimal lag time of cumulative delayed effects as 17 days (lag0_17), 18 days (lag0_18), 16 days (lag0_16) and 17 days (lag0_17), respectively. However, there were no statistical significances noticed in the elderly cases. Conclusion: There was a positive correlation between AQI and the number of TB cases in Beijing, and the effects of AQI on the number of TB cases in different genders and age groups were different.

A cross-sectional study on the status of tobacco use among junior middle school students in Shaanxi province / 中华流行病学杂志

Objective: To understand the rate on tobacco use and associated factors in junior middle school students in Shaanxi province. Methods: We used a multi-stage stratified random sampling method to select students from 30 junior middle schools in 10 areas of Shaanxi province in 2013. All the participants completed a self-administered questionnaire. Results: A total of 4 633 questionnaires were dispatched and 4 298 were qualified for further analysis. The current smoking rate of junior middle school students in Shaanxi was 6.5%, with rate in male (11.1%) higher than that of female students (1.7%). The current smoking rate of students in grade three (9.3%) was higher than those of students in grade one (3.5%) or in grade two (7.0%). The smoking rate of students with pocket money more than 31 Yuan per week was (10.0%) higher than those of students with pocket money less than 10 Yuan (4.6%) or 10-30 Yuan (6.3%) per week. Results from the logistic regression analysis showed that factors as: male, school located in the city, older age, with more pocket money, having smokers in the family and exposure to second hand smoking were high risk factors for current smoking. Conclusion: Rate on current smoking was high in junior middle schools students in Shaanxi, suggesting that comprehensive intervention programs be developed to reduce the rate of tobacco use in junior middle school students.

Application of ARIMA model in prediction of mortality rate of suicide in Hainan province / 中华流行病学杂志

Objective: To analyze the trend of suicide mortality in residents of Hainan province, and explore the application of time sequence model in the prediction of the mortality of suicide. Methods: The mortality data of suicide in residents of Hainan province between January, 2014 and December, 2016 were collected and analyzed with time sequence model and the mortality rate of suicide during January-June, 2017 in Hainan was predicted with the model. Results: During January, 2014 to June 2017, a total of 576 suicide cases were reported in Hainan, the mortality rate was 1.5/100 000. The established ARIMA model had good fitting for the suicide mortality in previous times and the prediction result was quite similar to the actual mortality, the predicted mortality rate was within the 95% confidence interval of the actual rate. Conclusion: The time sequence model for the prediction of suicide mortality in Hainan was "ARIMA (0, 1, 0) (0, 0, 0) (12)" , and the prediction effect of the model was better, which can be used to predict the suicide mortality in Hainan.

Influence of diurnal temperature range on influenza incidence in the elderly / 中华流行病学杂志

Objective: To understand the influence of diurnal temperature range (DTR) on influenza incidence in the elderly in Beijing and to conduct a subgroup analysis. Methods: The incidence data of daily influenza cases in the elderly and daily meteorological data from 2014 to 2016 in Beijing were collected for this study. A generalized additive model (GAM) was used to explore whether the relationship between daily influenza cases and DTR is a linear one. A distributed lag non-linear model (DLNM) was established to quantify the lagged effect of DTR on daily influenza incidence in the elderly. The model was also used to estimate the effects of DTR on daily influenza incidence among various subgroups. Results: A total of 4 097 influenza cases in the elderly were notified during study period. The mean DTR was 10.153 ℃. A linear relationship between daily influenza incidence and DTR was detected by using GAM. DTR was significantly associated with daily influenza incidence between lag0 and lag5 with a maximal effect at lag0. An 1 ℃ increase of DTR was associated with a 2.0% increase in daily influenza incidence in the elderly (95%CI: 0.9%-3.0%). The RR values of males, females, people aged 60-69 years, people aged ≥70 years were 1.018 (95%CI: 1.005-1.032), 1.021(95%CI: 1.007-1.035), 1.012 (95%CI: 1.002-1.022), 1.025 (95%CI: 1.012-1.039), respectively. The influencing time of DTR on females (lag6) was longer than males (lag2). Conclusions: DTR was associated with increased risk of influenza in the elderly in Beijing. It is necessary to take targeted measures in the elderly to control the incidence of influenza when DTR becomes greater.

Relations between pregestational body mass index, gestational weight gain and birth weight of neonates among women in the Southwest areas of China: A prospective cohort study / 中华流行病学杂志

Objective: To explore the effects of both pre-gestational BMI and gestational weight gain (GWG) on the birth weight of neonates. Methods: A total of 5 395 pregnant women were selected from the Southwest areas of China (Sichuan/Yunnan/Guizhou) and were divided into groups as pre-gestational underweight, normal weight, overweight and obesity, according to the WHO Recommendation on BMI Classification. Guidelines on Pregnancy weight were adopted from the Institute of Medicine to confirm the accuracy of GWG. Multinomial logistic regression model was used to assess the associations between pregestational BMI and GWG, on the birth weight of the neonates. Results: After adjusting for related confounders, low pre-gestational BMI appeared as a risk factor for SGA (OR=1.91, 95%CI: 1.47-2.50), and was also associated with the decreased risk of LGA (OR=0.55, 95%CI: 0.47-0.66). Inadequate GWG was both associated with the increased risk of delivering SGA (OR=1.57, 95%CI: 1.21-2.03) and the decreased risk of LGA (OR=0.48, 95%CI: 0.41-0.57). Pre-gestational overweight/obesity (OR=1.85, 95%CI: 1.58-2.17) and excessive GWG (OR=1.87, 95%CI: 1.67- 2.11) were both positively associated with the risks on LGA. Data from the stratified analysis indicated that inadequate GWG was positively associated with the risk of SGA among underweight or normal weight women (all P<0.05), but not with those overweight/obese women. Conclusions: Pre-gestational BMI and GWG were important influencing factors on the birth weight of neonates. Health education programs for pregnant women should be intensified and gestational weight gain should also be reasonably under control.