[Epidemiological characteristics of typhoid fever in Fujian Province, 2011-2022].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8. Results: A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members. Conclusions: Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

[Application of temporalis muscle flap in repair and reconstruction after the resection of tumor or necrotic foci following radiotherapy of nasopharyngeal carcinoma].

Objective: To summarize and popularize the application of temporalis muscle flap in repair and reconstruction after the resection of tumor or necrotic foci following radiotherapy of nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was made on the patients treated in the Department of Otorhinolaryngology Head and Neck Surgery of Xiangya Hospital between January 2019 and March 2021 who underwent surgical resection of tumor or necrosis of NPC after radiotherapy and temporalis muscle flap repair. The effect of the repair and the patients' postoperative conditions were analyzed. Results: A total 29 patients, 19 males and 10 females, aged from 33 to 65 years old, were included in the study, and were followed up for 6-35 months. Except for 2 patients who were not followed due to bleeding or special bacterial infection, the others' temporalis muscle flap healed well and no cerebrospinal fluid rhinorrhea or massive hemorrhage occurred. After the operation, all patients had no nasopharyngeal reflux or new open rhinolalia, and in some patients, the open rhinolalia even got relieved. Except for one case of depressed temporal fossa caused by infection and followed debridement and another one case of shallowed forehead wrinkles, the appearances of the other patients were basically symmetrical. Some patients had temporary mouth opening limitation after operation, and all of them recovered after rehabilitation exercises. Conclusions: The temporalis muscle flap can protect the skull base and internal carotid artery, and improve the quality of life of patients after the resection of NPC or necrotic foci. It is a reliable pedicled flap for repairing skull base defect with simple operation procedures and relatively few complications.

[Analysis on repetitive reporting of hepatitis B in Fujian province, 2016-2020].

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ2=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.

[Clinical study on endoscopic surgery for soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma].

Objective: To investigate the diagnosis and surgical treatment of patients with soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The clinical data of 7 NPC patients with soft tissue necrosis but not bone necrosis after radiotherapy were retrospectively analyzed.They were treated in Xiangya Hospital from 2015 to 2019. The clinical manifestations, diagnosis, treatment and prognosis were analyzed. The major clinical symptoms of the 7 patients were headache in 7 cases, hearing loss in 7 cases, long-term nasal malodor in 5 cases and epistaxis in 2 cases. All patients underwent high-resolution CT, MR and magnetic resonance angiography (MRA) before operation. All cases were treated with extended transnasal endoscopic approach under general anesthesia for resection of necrotic tissue. Five cases had their affected cartilaginous segments of the eustachian tubes partially or completely resected, 7 cases were treated with myringotomy and tube insertion, and 1 case was treated with pansinusectomy. Anti-inflammatory treatment were carried out during the perioperative period. The recovery of patients was observed and recorded through regular follow-up (from 6 months to 3 years) after the operation. Results: Nasopharynx soft tissue lesions can be seen in seven patients with bone cortex integrity by CT, and small bubble shadow can be seen at junction area between skull base soft tissue lesions and skull base bone surface.MR and MRA examination showed extensive inflammatory changes of nasopharynx. Parapharyngeal irregular necrotic cavity was found in 6 cases without central enhancement, demonstrating edema of surrounding soft tissue. The necrotic tissue of all 7 patients was surgically removed. Postoperative pathological examinations confirmed that all of them were necrotic soft and cartilaginous tissue, without tumor recurrence. The symptoms of all patients were significantly alleviated after operation. Headache was cured in 5 cases and relieved in 2 cases. Nasal malodor was cured in 4 cases and alleviated in 1 case. During the follow-up period, 5 patients survived, and 2 patients who had their eustachian tube reserved died. One of them died of nasopharyngeal hemorrhage caused by recurrent nasopharyngeal necrosis 3 months after the operation. Another case died of severe intracranial infection 6 months after operation. Conclusions: The diagnosis of skull base soft tissue necrosis after radiotherapy for nasopharyngeal carcinoma needs comprehensive analysis of radiotherapy history, clinical manifestations and imaging examination. High resolution CT, MR and MRA of skull base are very important for diagnosis. Early active removal of large-scale necrotic lesions under endoscope and partial or total resection of eustachian tube cartilage according to the involvement of eustachian tube cartilage is effective means of controling skull base soft tissue necrosis after radiotherapy. The effective means of necrosis can improve the quality of life of patients.

[Exploration of the treatment model for patients with advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease based on real-world data].

Objective: To explore whether combining treatment of chronic obstructive pulmonary disease (COPD) with anti-tumor therapy is better than that of tumor treatment alone in advanced non-small cell lung cancer (NSCLC) patients with COPD in the real world. Methods: The clinical data of 101 patients with advanced NSCLC complicated with COPD from January 1, 2015, to December 31, 2017, in the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively, including 99 males and two females, aged from 52 to 84 years[average (67±8) years]. Among the patients, 90 (89.1%) were smokers, with an average pack-year smoking index of (47±4) . The patients were divided into observation and control groups, depending on whether they received standardized anti-COPD supportive treatment. In the observation group, there were 36 patients, including 35 males and one female, aged from 54 to 84 years[ average (67±8) years], with an average pack-year of smoking (47±4). There were 65 patients in the control group, including 64 males and one female, aged from 52 to 83 years [average (67±8) years], with an average pack-year of smoking 47±4. There was no significant difference in the baseline data between the two groups. The primary outcome measures included the Objective response rate (ORR), disease control rate (DCR), disease-free survival (PFS), and overall survival (OS) of the two groups. An unpaired t-test was used to compare continuous variables between the observation and control groups. The Pearson chi-square test was used to compare categorical variables between the two groups. Kaplan-Meier survival curves were used to evaluate the median PFS and median OS of patients, and the log-rank test was used to assess differences between groups. Result: The ORR of the observation group and the control group was 22.6% (7 cases) and 22.2% (11 cases), respectively, with no significant difference (χ(2)=0.01, P=0.971). The DCR between the observation group and the control group was 58.1% (19 cases) and 57.8% (27 cases), with no significant difference (χ(2)=0.02, P=0.889). Median PFS in the observation group was 6.0 months, which was better than the 3.5 months in the control group (χ(2)=3.947, P<0.05). The median OS of the observation group was 18.0 months, which was better than the 15.0 months of the control group (χ(2)=4.083, P<0.05). Conclusions: Compared with the treatment of tumors alone, combination of anti-tumor therapy with anti-COPD therapy showed longer PFS and OS in patients with advanced NSCLC complicated with COPD.

[Recent progress in molecular targeted therapies for intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver cancer. The incidence of ICC has been significantly increased globally in recent years. The concealed onset of ICC usually results in late disease diagnosis. Liver resection is currently the only well-established treatment for ICC that may cure the disease, however, long-term survival rate is still unsatisfied due to the low resection rate and high recurrence rate. Local therapy combined with systemic chemotherapy is the main treatment for advanced or unresectable ICC, but the outcomes are still poor. With the in-depth understanding of the molecular mechanism of ICC and development of next-generation sequencing technology, multiple abnormal signaling pathways (RAS/MAPK, MET, EGFR) and gene mutations (FGFR2, IDH1/2) have been identified as potential therapeutic targets. Although there is still no approved targeted drugs for ICC, more than 100 clinical trials testing targeted therapy alone or in combination with chemotherapy are ongoing, among which some have shown promising application prospects. Molecular typing and personalized targeted therapy are important ways to improve the overall outcomes of ICC. This review summarized the recent advances in the targeted therapies for patients with ICC.

The clinical significance of MIA gene in tumorigenesis of lung cancer.

Lung cancer is a common malignant disease in humans. Both the incidence rate and death rate keep growing in recent years and the prognosis of lung cancer patients is disappointing. Melanoma inhibitory activity (MIA) is a secreted protein and a serum marker for metastasis of melanoma. MIA was reported as an oncogene in several cancers. But its role in lung cancer was unknown. In this study, MIA level was shown to be increased in peripheral blood of 216 patients with lung cancer. And it was expressed much higher in tumor tissues than the normal control. Moreover, MIA expression was associated with the clinical stage of lung cancer. When MIA was knocked down, the viability, migration and invasion of A549 cells were remarkably suppressed. But the cell apoptosis rate was enhanced reversely. In contrast, overexpression of MIA promoted cell proliferation, migration and invasion while cell apoptosis was inhibited. Mechanically, the anti-apoptosis marker Bcl-2 was increased and pro-apoptosis marker Bax was decreased after MIA was overexpressed in A549 cells, and vice versa. The level of PCNA and PI3K/mTOR signaling molecules was also increased when MIA was upregulated but declined after knockdown of MIA. In conclusion, MIA plays an oncogenic role in lung cancer and might be a potential marker for the diagnosis of lung cancer.

[Clinical analysis of Langerhans cell histiocytosis originating in the base of nasal skull].

Objective:To summarize the clinical features, diagnosis and treatment of Langerhans histiocytosis（LCH） which first appeared in the nasal skull base. Method:Ten cases of LCH with nasal and skull base symptoms were analyzed retrospectively. The clinical characteristics of LCH with nasal and skull base symptoms were summarized. The correlation of other systems involved in LCH was analyzed. Result:Among the 10 patients, the youngest was 1 year and 5 months, and the oldest was 8 years, the average age was 3 years. The main imaging manifestations were osteolytic changes and soft tissue invasion. Seven patients were monofocal and three patients were multifocal. For localized lesions, radical resection and follow-up chemotherapy were performed, and conservative treatment was performed for patients with multiple system involvement and obvious systemic symptoms. Eight patients survived, 2 died. Conclusion:LCH occurs frequently in children and has certain clinical characteristics. Single system and single lesion surgery have a better therapeutic effect, and can achieve a greater survival rate with follow-up chemotherapy.

[Analysis on association between incidence of hand foot and mouth disease and meteorological factors in Xiamen, 2013-2017].

Objective: To study the influence of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Xiamen, Fujian province, and provide scientific evidence for the early warning, prediction, prevention and control of HFMD. Methods: Correlation analysis and distribution lag nonlinear models (DLNM) analysis of meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours and the incidence of HFMD in Xiamen during 2013 to 2017 were conducted by using R3.4.3 software. Results: A total of 36 464 cases of HFMD were reported in Xiamen during 2013-2017, and the incidence showed an upward trend (F=40.359, P=0.008). The daily average relative humidity, daily average temperature and sunshine hours were positively correlated with the incidence of HFMD (r>0), and the daily average site pressure was negatively correlated with the incidence of HFMD (r<0). In the case of a lag of 0-5 days, when the daily average pressure of the station was higher than 1 005 hPa, the risk of HFMD gradually increased with the increase of air pressure, and the risk of disease decreased with the increase of lag days. The risk was highest when air pressure was 1 017 hPa and at the lag of 0 day (RR=1.14, 95%CI: 0.67-1.94). When the relative humidity was higher than 95%, the risk of HFMD gradually increased with the increase of relative humidity, and the lag time ranged from 0 day to 10 days, which was most obvious on the 4(th) and 5(th) days. The risk was highest when relative humidity was 100% and at the lag of 5 days (RR=1.32, 95%CI: 1.02-1.71). When the air temperature was >28 ℃ and <8 ℃, the risk of HFMD existed, but the lag time was inconsistent. The relative risk was highest during 15-20 days at low air temperature, and the lag time at high air temperature was mainly during 5-15 days. The risk was highest when air temperature was 28 ℃ and at the lag of 4 days (RR=1.10, 95%CI: 0.94-1.29). The sunshine time was >12 h and lag of 0-3 days was a risk factor for the incidence of HFMD. The risk was highest when sunshine time was 13 h and the lag of 0 day (RR=1.20, 95%CI: 1.05-1.36). Conclusion: Meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours were associated with the incidence of HFMD with certain lag in Xiamen. So, it is suggested to use these data in the early warning system of HFMD.

Protective effects of melatonin on mitochondrial biogenesis and mitochondrial structure and function in the HEK293-APPswe cell model of Alzheimer's disease.

OBJECTIVE: The effects and mechanisms of melatonin on Alzheimer's disease (AD) are still not researched thoroughly. 20E2 cells (HEK293-APPswe cells) are a cellular model of AD. The modulation effects of melatonin on the structure and function of mitochondria in 20E2 cells need to be studied. MATERIALS AND METHODS: The Alzheimer's disease (AD) cell model was assessed for cell viability, expression levels of mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory factor 1 [NRF1], nuclear respiratory factor 2 [NRF2], mitochondrial transcription factor A [TFAM]), mitochondrial membrane potential, Na+-K+-adenosine triphosphatase (ATPase) and cytochrome C oxidase activity, adenosine triphosphate (ATP) level, mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio, and mitochondrial structure with and without melatonin. RESULTS: Melatonin improved 20E2 cell viability, expression of mitochondrial biogenesis factors (PGC-1α, NRF1, NRF2, TFAM), mitochondrial membrane potential, Na+-K+-ATPase, and cytochrome C oxidase activity, ATP level, mtDNA/nDNA ratio, mitochondrial structure, and decreased amyloidogenic amyloid precursor protein processing. CONCLUSIONS: Mitochondrial biogenesis disorder is associated with the pathogenesis of AD through PGC-1α-NRF-TFAM pathway, and melatonin improves the mitochondrial structure and function by enhancing mitochondrial biogenesis and decreasing amyloidogenic APP processing in Alzheimer's disease.

Scale-Dependent Waylaying Effect of Pollinators and Pollination of Mass-Flowering Plants.

Pollinators foraging for food resources can be waylaid by mass-flowering plants located in their foraging pathway in landscapes. The waylaying effect of pollinators is often studied at a single spatial scale; to date, little is known about the best spatial extent at which waylaying effect of pollinators can be measured. In this study, we selected a landscape with mass-flowering tufted vetches to determine the spatial scale of waylaying effect of honey bees as well as the consequence of waylaying effect on vetch pollination service. The spatial scale of waylaying effect was determined by the strongest association between honey bee density and distance, selected from a gradient of nested circular buffers centering on apiaries in three different locations. Linear models were used to predict the influence of flower visitor densities on pollination service. For our landscape, honey bee densities were best associated with distances at spatial scales of 500 m, 1150 m, and 1400 m respectively for the three locations of apiaries. Honey bee was the only pollinator whose density displayed a positive relationship with pollination service. At the scales of effect, honey bee density and pollination service declined along the distance. Our findings suggest that the waylaying effect of pollinators needs to be examined at a specific spatial scale and farmers who use honey bees to pollinate their mass-flowering crops need to consider the spatial scale of waylaying effect of pollinators in order to maximize pollination service within agricultural ecosystems.

[Progress on surgical treatment of intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma(ICC)is a primary liver cancer with its incidence only after hepatocellular carcinoma.Liver resection is currently the only established effective treatment for patients with ICC.However,the resectability of ICC is low and the long-term survival after surgery is far from satisfactory. With the advances in the understanding of the biological characteristics and prognostic characteristics of ICC, surgical strategy and techniques have improved in recent years, and the long-term survival has also been increased. The accurate clinical diagnosis of ICC, R0 resection, routine lymphadenectomy, effective adjuvant therapy after R0 resection, and multidisciplinary treatment including re-hepatectomy for recurrent ICC are important for achieving an optimal outcome.Down-staging management for patients with unresectable ICC may provide a chance of R0 resection in some patients. Further research on the biological heterogeneity of ICC,and the improvement of surgical treatment or the establishment of new treatment methods are the main research directions in the future.