Currently, the global malaria epidemic is still severe. China was certified malaria-free by WHO in 2021; however, there is a risk of cross-border importation and secondary transmission of malaria via aircrafts and through land bordering countries in China because of the complex environments in border areas between China and neighboring malaria-endemic countries, notably the explosive growth in the malaria epidemic in Myanmar in China-Myanmar border areas. This article summarizes typical cases of secondary transmission caused by imported malaria across the world, and proposes responses to cross-border importation and secondary transmission of malaria in non-border and border areas of China, in order to effectively reduce the risk of malaria importation and secondary transmission and consolidate the hard earned malaria elimination achievements.

Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

ObjectiveTo investigate the prognostic differences between primary biliary cholangitis （PBC） patients positive for different autoantibodies and the risk factors for poor prognosis， and to facilitate early and effective intervention for PBC patients. MethodsA total of 141 patients who were diagnosed with PBC for the first time in Fenyang Hospital of Shanxi Province from January 2018 to December 2023 were enrolled and divided into group A （80 patients positive for anti-mitochondrial antibody M2 ［AMA-M2］ alone）， group B （36 patients positive for AMA-M2 and anti-gp210 antibody）， and group C （25 patients positive for AMA-M2 and anti-sp100 antibody）， and the three groups were compared in terms of general information， laboratory markers， and prognosis. The Globe score was used for prognostic evaluation， and a Globe score of<0.3 and the absence of liver cirrhosis at the time of confirmed diagnosis were defined as good prognosis， while a Globe score of ≥0.3 or the presence of liver cirrhosis at the time of confirmed diagnosis were defined as poor prognosis. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the prognosis of PBC patients； the receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC） was calculated. ResultsCompared with group A， groups B and C had a significantly higher proportion of male patients， a significantly higher detection rate of liver cirrhosis， significantly higher levels of ALT， TBil， and ALP， and significantly lower levels of PLT and Alb （all P<0.05）. The Globe score was calculated based on related indicators after treatment with ursodeoxycholic acid （UDCA） for 1 year， and the results showed that there was a significant difference in prognosis between the three groups （P<0.001）， and compared with group A， groups B and C had a significantly higher proportion of patients with a Globe score of ≥0.3 （P<0.05） and a significantly higher rate of suboptimal response to UDCA （P<0.05）. The univariate Logistic regression analysis showed that anti-gp210 antibody， anti-sp100 antibody， UDCA response， PLT， Alb， ALT， TBil， and ALP were associated with the prognosis of PBC patients （all P<0.05）. The variables meeting related conditions were included in the multivariate Logistic regression analysis， and the results showed that anti-gp210 antibody （odds ratio ［OR］=4.959， 95% confidence interval ［CI］： 1.112 — 22.122， P=0.036）， anti-sp100 antibody （OR=21.666， 95%CI： 1.542 — 304.449， P=0.023）， Alb （OR=0.899， 95%CI： 0.814 — 0.994， P=0.038）， PLT （OR=0.974， 95%CI： 0.963 — 0.985， P<0.001）， and UDCA response （OR=10.275， 95%CI： 1.047 — 100.831， P=0.046） were independent influencing factors for the prognosis of PBC patients. The ROC curve analysis showed that PLT had the best performance in predicting the prognosis of PBC patients， with an AUC of 0.824， a sensitivity of 85.7%， and a specificity of 71.7%. ConclusionPatients with dual positivity for AMA-M2 and anti-gp210 antibody， as well as those with dual positivity for AMA-M2 and anti-sp100 antibody， tend to have a poorer prognosis and a higher rate of suboptimal response to UDCA. Furthermore， positivity for anti-gp210 antibody， positivity for anti-sp100 antibody， thrombocytopenia， hypoalbuminemia， and suboptimal response to UDCA all indicate poor clinical prognosis.

Objective To explore the epidemiological characteristics and treatment outcomes of venomous snake bites in Yunnan Province from 2023 to 2024.Methods A retrospective analysis was performed on 1,727 snakebite cases collected from 16 administrative regions in Yunnan Province between January 2023 and December 2024,focusing on the following indicators:(1)demographic characteristics(age and gender distribution);(2)characteristics of injury events(location,time distribution,and affected body parts);(3)composition of venomous snake species;(4)clinical features and treatment protocols;(5)efficacy evaluation indicators(time for local symptom relief,duration of hospital stay,and follow-up results).Results High-incidence areas for snake bites in Yunnan Province included Wenshan(308/1727),Kunming(285/1727),Qujing(270/1727),Lincang(139/1727),Baoshan(120/1727),and Dali(105/1727),with incidents primarily occurring from June to September.The most frequently encountered venomous snake species were Ovophis and Trimeresurus,known for their hemotoxic venom.Bite victims were mainly young adults.Clinical manifestations primarily included pain and swelling,with bites mainly occurring on limbs and in mountainous or forested areas.Anti-venom treatment concentrated on anti-ancistrodon acutus serum.Swelling generally subsided within 2(2,3)days,with an average hospital stay of 4(3,5)days.96.46%of patients receiving standardized treatment fully recovered,with a follow-up disability rate of 0.35%.Conclusion The incidents of venomous snake bites in Yunnan Province have significant regional and seasonal concentration,with Wenshan,Kunming,Qujing and other areas being high-risk areas.The peak period of incidents is from June to September in summer,and the main types of snakes causing injuries are those containing blood toxins;The victim group is mainly young people,and bites often occur in the limbs,with typical symptoms of pain and swelling;The main treatment is anti snake serum;Snake bite patients who receive formal diagnosis and treatment have a higher recovery rate and a lower follow-up disability rate,but there is still a need to raise public awareness of standardized diagnosis and treatment for snake bites.

Objective: To investigate the regulatory role of Porphyromonas gingivalis(Pg) infection on the EGFR/GSK3β signaling axis, and its impact on epithelial-mesenchymal transition(EMT) and cetuximab(Ctx) resistance in esophageal squamous cell carcinoma(ESCC). Methods: Single cell RNA sequencing was employed to perform differential analysis of cellular subpopulations, identifying differentially expressed genes in ESCC tissues infected and non-infected with Pg. IHC was conducted to assess the expression of Pg and epidermal growth factor receptor(EGFR) in ESCC tissues. Western blot, RT-PCR, and IF staining were performed to evaluate EGFR expression in Pg infected ESCC cell lines KYSE70 and TE1. ESCC cells were treated with Pg and EGFR inhibitor Ctx, and divided into four groups: control(NC) group, Pg group, Ctx group, Pg+Ctx group. Cell proliferation, migration and invasion abilities were evaluated using CCK-8, plate cloning, wound healing and Transwell assay. Western blot analysis was performed to detect the expression of EMT and EGFR/GSK3β signaling pathway-associated proteins and their phosphorylation levels. Transforming growth factor-β1(TGF-β1) was used to induce EMT in ESCC cells, promoting a transition from the epithelial phenotype to mesenchymal-like phenotype. The differential effects of Ctx on these two phenotypic states were subsequently compared. Results: Epithelial cells were predominantly enriched in Pg-positive tissues, and Pg infection promoted the upregulation of EGFR expression in ESCC cells. Compared to the NC group, Pg treatment significantly enhanced the proliferation, invasion and migration capabili-ties of ESCC cells, and also increased chemoresistance to Ctx and reduced its antitumor efficacy. Pg induced EMT in ESCC cellsviathe EGFR/GSK3β signaling pathway. Notably, Ctx exhibited markedly weaker inhibitory effects on mesenchymal-like cells compared to epithelial ESCC cells. Conclusion Pg promotes ESCC cells proliferation, invasion and migration by regulating EMT through the EGFR/GSK3β signaling pathway, and enhances chemoresistance to Ctx.

Objective To observe MRI features of H3K27M mutant type and wild type astrocyte differentiated diffuse midline glioma(DMG)in spinal cord.Methods Totally 91 patients with astrocyte differentiation diffuse midline glioma(DMG)in spinal cord confirmed by pathology were retrospectively enrolled and divided into mutant group(n=44)and wild group(n=47)according to H3K27M status.Clinical and MRI manifestations were compared between groups,and logistic regression analysis was used to screen the impact factors of H3K27M mutation.Results The incidence of peritumoral edema and spinal cord cavity in mutant group were lower than those in wild group(both P＜0.05),while no significant difference of other parameters was found between groups(all P＞0.05).All clinical and MRI parameters were included in logistic regression analysis,and the result showed that they were not influencing factors of H3K27M mutation(all P＞0.05).Conclusion The incidence of peritumoral edema and spinal cord cavity in spinal cord H3K27M mutant type astrocyte differentiated DMG were lower than those of wild type,yet not sufficient to be regarded as impact factors for predicting H3K27M mutation of DMG.

This article introduced Professor Wang Xingkuan's academic thoughts and clinical experience in diagnosing and treating burning mouth syndrome(BMS)in perimenopausal women based on the theory of"yin injury and internal dryness".Professor Wang advocates the principle of"treating the root cause of the disease and harmonizing multiple organs".Starting from the unique physiological characteristics of perimenopausal women,he believes that the BMS in perimenopausal women should be attributed to the kidneys,liver,heart,and small intestine.The fundamental cause of the disease is the deficiency of kidney essence and the gradual decline of liver blood,and the key to the onset is the dryness of the kidney,liver,heart,and small intestine.In treatment,the overall strategy is to take"yin injury and internal dryness"as the main guideline,focusing on the liver and kidney,with nourishing and replenishing the liver and kidney as the main approach and clearing heat and moistening as auxiliary methods.The basic formula for treating BMS is a combination of Erdong Decoction and Baihe Dihuang Decoction,which has shown significant clinical efficacy.

AIM:To investigate the efficacy and anti-hepatic fibrosis of alfacalcidol combined with ursodeoxycholic acid(UDCA)in primary biliary chol-angitis(PBC).METHODS:Seventy cases of PBC pa-tients with 25 hydroxyvitamin D(25(OH)D3)＜50 nmol/L,admitted to Fenyang Hospital in Shanxi Province from June 2022 to June 2023,who met the inclusion criteria,were randomly divided into 35 cases in the treatment group and 35 cases in the control group.and the treatment group was treat-ed with alfacalcidol combined with UDCA;the con-trol group was treated with UDCA alone;after 6 months of treatment,the patients were examined for 25(OH)D3,platelets,liver function,immunoglob-ulin,liver stiffness(LSM),and adverse drug reac-tions,and the FIB-4 index,APRI score,GLOBE score,and UK-PBC score were calculated.Measurements that satisfied the normal distribution were ex-pressed as(x)±s,and comparisons between the two groups were made with the t-test;those that did not satisfy the normal distribution were expressed as M(P25,P75)was used to express the information,and the Mann-Whitney U test was used to compare the two groups.Response rates were compared with the chi-square test.RESULTS:The response rates in the control and experimental groups after treatment were 42.85％and 71.42％;y-glutamyl transpeptidase(GGT)was 160(128,194)and 85(72,102)U/L;alkaline phosphatase(ALP)was 156(123,264)and 110(56,141)U/L;respectively;im-munoglobulin M(IgM)were 3.51±0.84 and 2.71±0.81 g/L;25(OH)D3 was 40.21±3.25 and 57.06±14.76 nmol/L;respectively,liver hardness was 10.8(8.3,15.1)and 8.9(6.7,12.2)KPa;respectively,and FIB-4 index was 2.28(0.99,3.66)and 1.46(0.97,2.55);respectively,APRI scores were 0.65(0.33,1.09)and 0.30(0.17,0.53);respectively,GLOBE scores were 0.85±0.73 and 0.13±0.51,and UK-PBC scores were 0.024(0.018,0.060)and 0.021(0.012,0.033),and the differences were statistically signifi-cant(all P＜0.05).CONCLUSION:Alfacalcidol com-bined with UDCA significantly increased the treat-ment response rate of PBC patients compared with UDCA alone,and alfacalcidol improved hepatic fi-brosis to a certain extent,contributing to the im-provement of PBC without adverse effects.

Objective:To analyze the cause of varicocele (VC) recurrence and investigate the efficacy of sub-inguinal microsurgical varicocelectomy (MV) for recurrent VC.Methods:All of 16 inpatients diagnosed as recurrent VC, in the Department of Andrology of the Affiliated Hospital of Qingdao University from 2015 April to 2019 April, were performed sub-inguinal MV. The age of the inpatients was 18-36 years old, median 27 years old.5 cases were originally performed retroperitoneal high ligation of spermatic vein and other 11 cases were originally performed laparoscopic varicocelectomy. During the review one to three years after the previous operation, all of 16 patients were diagnosed as VC recurrence. The complains of these patients during the review included male subfertility (10 cases) and scrotal pain (12 cases), in which 6 cases’ complains were male subfertility with scrotal pain. After admission, 13 patients were classified as Grade Ⅲ (left in 8 cases, bilateral in 5 cases) and 3 patients as Grade Ⅱ (all left). The median of their visual analogue scale (VAS) was 2.5. Color doppler flow imaging (CDFI) grading showed: Grade Ⅲ in 12 cases (left in 7 cases, bilateral in 5 cases), Grade Ⅱ in 4 cases (all left). Particularly, 12 of them were Graded as Ⅲ simultaneously accompanying with Nut-cracker Phenomenon (NCP). Preoperative tests showed that the average serum testosterone was (16.2±4.9)nmol/ml, the average sperm concentration was (11.8±3.9)×10 6/ml and the progressive motility rate (PR) was (24.4±4.2)%. All of the patients were performed sub-inguinal MV using general anesthesia and supine position. The spermatic cords were clearly exposed and padded up by inserting gauze strips under them. During the operation, the field was magnified 4-6 times with the microscope. Then all of the dilated external and internal spermatic veins were ligated, at the same time the internal spermatic artery and lymph vessels were well preserved. During these operations, 11 patients underwent left-side MV, while other 5 did bilateral MVs. During these MVs, we found twisted and dilated external and internal spermatic veins in all cases and well preserved the internal spermatic arteries and lymph vessels. The number of ligated left and right external spermatic veins were(2.1±0.6) and (1.4±0.5)respectively and the number of ligated left and right internal spermatic veins were (10.1±1.1) and (6.6±0.5) respectively. We also found out(1.3±0.5) internal spermatic arteries and (3.0±1.0)lymph-vessels on left side. On right side, there were (1.4±0.5) internal spermatic arteries and (2.6±0.5) lymph-vessels respectively. At last, we summarily analyzed the pre-operative and post-operative VAS, serum testosterone, CDFI and semen analysis data. Results:All of the 16 sub-inguinal MVs were successfully performed. All patients were reviewed comprehensively 6 months after MV. The reviewed results showed that the post-operative VAS was significantly reduced ( Z=-2.994, P<0.05), palpable scrotal vessels disappeared and Valsalva tests were negative. No obvious reflux of internal spermatic veins were detected by CDFI. Interestingly, the sperm concentration and motility were both significantly improved 6 months after MV ( P<0.05), while there was not remarkable increase of the serum testosterone after MV ( P>0.05). During the follow up, no testicular atrophy, hydrocele and other complications were found. Up to submission, five of the ten patients who presented for male subfertility have impregnated their wives. Conclusions:The most possible cause of VC recurrence could be the omission of the external and internal spermatic veins, particularly in the grade Ⅲ VC patients or VC accompanied with NCP. The sub-inguinal MV, which can discover more twisted spermatic veins and at the same time preserve the spermatic artery and lymph-vessels, shows better clinical efficacy than other procedures.

Objective To study the protective effect of human urinary kallidinogenase (HUK) on focal cerebral ischemia-reperfusion injury in rats via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Methods Eighty adult male SD rats were randomly divided into sham-operated group,model group,HUK group and LY294002 group (n=20).The rat focal cerebral ischemia-reperfusion models in the latter three groups were established by suture-occluded method;model group and HUK group were,respectively,injected with sterile saline or HUK 1.0 mL/kg via tail vein 3 h after reperfusion;rats in the LY294002 group accepted intraventricular injection of 10 nmol LY294002 before cerebral ischemia and caudal vein injection of 1.0 mL/kg HUK three h after reperfusion.Twenty-four h after reperfusion,Neurological Deficit Scale was performed,cerebral infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and protein expressions of Akt,phosphorylated (p)-Akt and Caspase-3 were assessed by Western blotting.Results As compared with those in the model group,the Neurological Deficit Scale scores were significantly lower,cerebral infarct volumes were significantly smaller,p-Akt expression was significantly increased,and Caspase-3 expression was significantly decreased in the HUK group (P＜0.05).As compared with those in the HUK group,Neurological Deficit Scale scores were significantly higher,infarction volumes were significantly increased,p-Akt expression was significantly decreased,and Caspase-3 expression was significantly increased in the LY294002 group (P＜0.05).Conclusion HUK has neuro-protective effect through up-regulating p-Akt expression in the PI3K/Akt signaling pathway and down-regulating Caspase-3 expression.