Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

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.

Objective We aimed to explore the mechanism of Ziyin Mingmu Formula in improving retinitis pigmentosa.Methods Twenty SD rats were randomly divided into the blank serum group and the Ziyin Mingmu Formula containing serum group using a random number table method,with 10 rats in each group.The rats in the Ziyin Mingmu Formula containing serum group were given Ziyin Mingmu Formula(46.875 g/kg),while the rats in the blank serum group were given distilled water.The Ziyin Mingmu Formula containing serum and blank serum were prepared.Analysis of chemical components in Ziyin Mingmu Formula containing serum using liquid chromatography-mass spectrometry technology.Adult retinal pigment epithelial cell line-19(ARPE-19)cells were treated with tunicamycin to induce endoplasmic reticulum stress injury model.The optimal volume fraction of Ziyin Mingmu Formula containing serum was screened by CCK-8.ARPE-19 cells were divided into the blank group,the model group,the blank serum group,the Ziyin Mingmu Formula containing serum group and the tauroursodeoxycholic acid group,each group is intervened separately.After 24 hours of intervention,the morphological observation of cells was performed using a multi-time dynamic cell function analysis system,cell survival rate was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PI,and protein and mRNA expressions of 78 kDa glucose regulated protein(GRP78),inositol-requiring enzyme 1(IRE1)and activating transcription factor 6(ATF6)were detected by Western blotting and ddPCR.Results The main chemical components in Ziyin Mingmu Formula containing serum were obtained by liquid chromatography-mass spectrometry analysis,such as arbutin,salicylic acid,luteolin,Salvianolic acid A,erysovine,taurine,quercetin,maltol,baicalin,and danshensu.Compared with the model group,the number of cells in Ziyin Mingmu Formula containing serum group increased,the growth was more uniform,and the floating dead ARPE-19 cells and fragments decreased.The cell survival rate of Ziyin Mingmu Formula containing serum group and taursodeoxycholic acid group increased,and the cell apoptosis rate decreased(P<0.05).The protein expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group were decreased,and IRE1 and ATF6 in taursodeoxycholic acid group were decreased(P<0.05).The mRNA expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group and tauroursodeoxycholic acid group were decreased(P<0.05).Conclusion Ziyin Mingmu Formula can reduce the cell apoptosis of ARPE-19 cells induced by endoplasmic reticulum stress,and its molecular mechanism is related to down-regulating the expression of GRP78,IRE1,ATF6 and inhibiting the endoplasmic reticulum stress response.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Retinitis pigmentosa(RP)is a degenerative blinding disease characterized by the loss of the function of photoreceptor and retinal pigment epithelium. The activation of endoplasmic reticulum stress is a cellular defense regulatory mechanism, aimed at restoring the stability of endoplasmic reticulum function by self-regulation through a series of molecular signaling pathways. Rhodopsin mutation is a common cause of RP. Misfolding and retention of rhodopsin in endoplasmic reticulum and apoptosis of photoreceptor cells and retinal pigment epithelial cells induced by endoplasmic reticulum stress can lead to the occurrence and development of RP. This paper discusses endoplasmic reticulum stress and its role in the pathogenesis of RP and the role of endoplasmic reticulum stress inhibitors, traditional Chinese medicine and chemical drugs in regulating endoplasmic reticulum stress in RP treatment was summarized, in order to provide theoretical basis for endoplasmic reticulum stress in the clinical application of RP and provide new ideas for the research, prevention and treatment of RP.

ObjectiveTo study the effect of Ziyin Mingmu Formula （滋阴明目方） on retinitis pigmentosa mice and its possible mechanism. MethodsSixty rd10 mice were randomly divided into model group， vitamin A group， and Ziyin Mingmu Formula low-， medium-， and high-dose groups， 12 mice in each group； twelve C57BL/6 mice as the blank group. The mice in Ziyin Mingmu Formula low-， medium-， and high-dose groups were given 13.5， 27.0 and 54.0 g/（kg·d） of Ziyin Mingmu Formula by gavage， respectively； mice in the Vitamin A group were given 750 IU/（kg·d） of vitamin A soft capsule by gavage； mice in the blank group and model group were given 13.5 ml/（kg·d） of physiological saline by gavage. Each group was gavaged once a day for 28 days. Fundus photography and optical coherence tomography were used to detect the morphology of the fundus and retina， TUNEL method was used to detect apoptosis， microtitre digital PCR and immunofluorescence double staining were used to detect glucose-regulated protein 78 （GRP78）， inositol-requiring enzyme 1 （IRE1）， activated transcription factor 6 （ATF6）， and C/EBP homologous protein （CHOP） mRNA and protein expression levels. ResultsIn the model group， optic discs were yellowish， fundus was atrophic with large pigmentation. The retinal blood vessels were thinned， a large number of vascular white sheaths were seen， the retinal cell nuclei disorganised， and a large number of apoptotic cells were seen； the fundus conditions of the mice in all dosages of Ziyin Mingmu Formula and the vitamin A group were improved to varying degrees compared with those of the model group， the apoptotic cells reduced， with Ziyin Mingmu Formula middle- and high-dose groups showing more significant improvement. Compared with the blank group， the retinal thickness of mice in the model group reduced， and the expression of GRP78， IRE1， ATF6， CHOP mRNA and protein elevated （P＜0.01）. Compared with the model group， retinal thickness increased and GRP78， IRE1， ATF6 mRNA and protein expression decreased in the vitamin A group and Ziyin Mingmu Formula medium- and high-dose groups； CHOP mRNA and protein expression decreased in low-， medium-， and high-dose groups of Ziyin Mingmu Formula （P＜0.05 or P＜0.01）. Compared with vitamin A group and the low-dose group of Ziyin Mingmu Formula， retinal thickness increased in the high-dose group of Ziyin Mingmu Formula （P＜0.01）. Compared with vitamin A group， GRP78， ATF6， IRE1， and CHOP mRNA expression decreased in the medium- and high-dose groups of Ziyin Mingmu Formula， and GRP78 and CHOP protein expression decreased （P＜0.05 or P＜0.01）. Compared with the low-dose group of Ziyin Mingmu Formula， CHOP protein expression reduced in the medium- and high-dose groups of Ziyin Mingmu Formula （P＜0.01）. ConclusionZiyin Mingmu Formula can reduce apoptosis of retinal tissues by inhibiting the endoplasmic reticulum stress response， thus slowing down the progression of retinopathy and protecting visual function in a dose-dependent manner.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective To investigate the protective effects of 2-methoxyestradiol(2ME)against hypoxic pulmonary hypertension(HPH)in neonatal rats.Methods Ninety-six Wistar neonatal rats were randomly divided into a normoxia group,a hypoxia group,and a hypoxia+2ME group,with each group further subdivided into 3-day,7-day,14-day,and 21-day subgroups,containing eight rats each.The hypoxia and hypoxia+2ME groups received daily subcutaneous injections of saline and 2ME(240 μg/kg),respectively,while the normoxia group was raised in a normoxic environment with daily saline injections.Right ventricular systolic pressure(RVSP)was measured using the direct pressure method.Pulmonary vascular morphology was assessed using hematoxylin and eosin staining,with metrics including the percentage of medial thickness of small pulmonary arteries relative to the external diameter(MT%)and the cross-sectional area of the media of small pulmonary arteries relative to the total cross-sectional area(MA%).Immunohistochemistry was used to detect the expression levels of hypoxia-inducible factor-1α(HIF-1α)and proliferating cell nuclear antigen(PCNA)proteins,while real-time quantitative PCR was used to to assess HIF-1α and PCNA mRNA levels.Results Compared to the normoxia group,the hypoxia and hypoxia+2ME groups showed increased RVSP and upregulated HIF-1α and PCNA protein and mRNA expression levels at 3,7,14,and 21 days after hypoxia(P<0.05).Furthermore,at 7,14,and 21 days after hypoxia,the hypoxia group showed increased MT%and MA%(P<0.05).In comparison to the hypoxia group,the hypoxia+2ME group exhibited reduced RVSP and downregulated HIF-1α and PCNA protein and mRNA expression levels,along with decreased MT%and MA%at 7,14,and 21 days after hypoxia(P<0.05).Conclusions 2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1α and PCNA and reducing pulmonary vascular remodeling.

Objective:To observe the clinical phenotype of patients with CACNA1F gene variant. Methods:A retrospective clinical study. From January 1, 2022 to October 1, 2023, 36 patients with CACNA1F gene mutation-related eye diseases diagnosed by clinical examination and genetic testing in Changsha Aier Eye Hospital and Jinan Purui Eye Hospital were included in the study. All patients underwent best-corrected visual acuity (BCVA), medical optometry, fundus color photography, optical coherence tomography, full-field electroretinography (ERG), nystagmus examination, and genetic whole-exon sequencing. BCVA was performed using log visual acuity charts and converted to (logMAR). The nystagmus examination was performed using a helmet-mounted multifunctional video eye movement recording system. The clinical phenotypic characteristics were observed. Results:At total of 36 patients were male, aged was (6.69±5.26) years. There were 36 cases of myopia (38.89%, 14/36), and the spherical equivalent was (?3.01±4.84) D. There were 14 different genetic variants including 7 cases of pathogenic variants, 20 cases of suspected pathogenic variants and 9 cases of unknown pathogenic variants, respectively. logMAR BCVA was 0.67±0.27; 26 patients had optic nerve atrophy (72.22%, 26/36); 6 had optical nerve hypoplasia (16.67%, 6/36). Fundus pigment dysplasia with mild iris transillumination was found in 4 cases (11.11%, 4/36). There were 5 cases of foveal dysplasia (Thomas grade) 1 (13.89%, 5/36). In full-field ERG examination, the B-wave reduction of the maximum mixed reaction of dark adaptation showed a negative waveform, and the amplitude of the shock potential was seriously reduced. The main phenotypes were residual type (residual dark adaptation 0.01 reaction wave and bright adaptation 3.0 reaction wave, and the response decreased at 30 Hz to a double-peak wide wave), dominant type of bright adaptation decreased (all light adaptation extinguished, all dark adaptation extinguished), and total extinction type (all light adaptation extinguished). Among them, 10 cases presented with residual ERG (27.78%, 10/36), 8 cases with photopic reduced ERG (22.22%, 8/36) and 18 with extinguished ERG (50.00%, 18/36). Low amplitude and high frequency pendulum (PLAHF) nystagmus waverforms were found in 32 cases (88.89%, 32/36), head oscillation in 27 cases (75.00%, 27/36) and chin up abnormal head posture in 26 cases (72.22%, 26/36), respectively.Conclusions:CACNA1F Gene variant eye diseases had diverse clinical phenotype. Clinical phenotype of PLAHF nystagmus is closely related with CACNA1F gene variant eye disease.