Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6％vs 35.7％,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1％vs 86.9％,P=0.001)and having cardiovascular disease(20.1％vs 32.1％,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95％CI:1.89-6.27,P＜0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95％CI:0.626-0.709,P＜0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22％and 27.78％of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.

Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6％vs 35.7％,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1％vs 86.9％,P=0.001)and having cardiovascular disease(20.1％vs 32.1％,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95％CI:1.89-6.27,P＜0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95％CI:0.626-0.709,P＜0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22％and 27.78％of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm² and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm² and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 µg/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0 ± 3.0%, and 48.0 ± 2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0–28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

Objective: To investigate the effect of skin soft tissue expansion on repair of large area of scars on extremities. Methods: Twenty-five patients with large area of scars on extremities were admitted to our department from June 2007 to October 2014. There were 14 males and 11 females, aged 4 to 36 years. Operations were performed under local infiltration anesthesia or general anesthesia. In the first stage, 1 to 5 cylindrical expanders with capacities of 250 to 600 mL were placed at left or right sides or at upper or lower parts of the scars. In the second stage, scars of 21 patients were repaired with expanded transverse propulsive and lateral flaps, and scars of 4 patients were repaired with expanded perforator flaps whose pedicles were perforators of brachial artery, superior ulnar collateral artery, or posterior interosseous artery according to areas and shapes of the scars. The secondary wound areas ranged from 13 cm×7 cm to 34 cm×18 cm after dissolution or excision of scars. The areas of flaps ranged from 13 cm×7 cm to 20 cm×12 cm. The donor sites were sutured directly. The flaps after operation and follow-up of patients were observed and recorded. Results: All expanded flaps survived after operation. And the superficial distal part of flap whose pedicle was perforator of posterior interosseous artery in one patient was with necrosis, and other flaps survived well. During follow-up of 3 to 15 months after operation of the second stage, color and texture of flaps were similar to surrounding skin, while extremities of donor sites were thinner and auxiliary incisional scars formed after expansion. Conclusions Expanded flap is a good way to repair large area of scar on extremities. Bilateral skin of scar is the first choice of donor site of expanded flap. If there isn′t enough skin for expanding on bilateral sides, expanded perforator flap designed at upper or lower part of the scar is another choice to repair the scar.

Objective: To sum up the clinical manifestations and the method for repairing of secondary deformities of postoperation of hypospadias. Methods: Applying balanus tissue flaps and urethral meatus plastic could correct the flat balanus and prevent urethral meatus from falling back. Resecting scar completely in penis and rebuilding urethral tissues could treat secondary curved penis. Applying modified penile augmentation which involved girth enhancement by a free dermal-fat graft and penile elongation (suprapubic skin advancement-ligamentolysis) could correct shorter and much smaller penis. Results: Among January 1st 2007 to December 31st 2016, 62 cases were treated.All of them were male. Their ages were from 14 to 34 years old.55 cases were followed up from 6 months to 9 years after operations, but 7 cases could not be followed up because of the change of addresses and phone numbers.All patients achieved excellent cosmetic result. None of them had complications like urethral fistula. Conclusions After operations of hypospadias, the secondary deformities may happen when the children grow up.And these deformities always need to be corrected with operations. Balanoplasty, correction of penis and the penile augmentation are good methods for secondary deformities.Consequently, a good penis appearance and function can be acquired.

Objective: To investigate the therapeuctic effect of one-stage reconstruction of distal urethra with free graft of tublar oral mucosa. Methods: Two strips of oral mucosa graft( 0.4—0.6 cm in width), were harvested and sutured around an oiled silk roll to form mucosa tube. The mucosa tube was used to reconstruct distal urethra. Postoperative pressure dressing and earlier urination were recommended. Results: From May 2007 to October 2015, 16 cases with distal urethra defect or stenosis were treated with this method. The urethra defect was 2—4 cm in length. Urethral fistula happened in 3 patients. All the other 13 cases healed primarily. 10 cases were followed up for 1—5 years by telephone with normal function. Conclusions One-stage reconstruction with free graft of bulbar oral mucosa is suitable and reliable for distal urethra defect less than 4 cm in length.

OBJECTIVETo discuss the methods for urethral external meatus and glanuloplasty after correction of hypospadias.

METHODSThe V shape flap on the dorsal side of glan, combined with the bilateral glan flaps were moved to the ventral side. The flap at the ventral side of urethral external meatus was turned over. Then the urethral external meatus was repositioned to the top end of glan with the ventral defects covered by the dorsal flaps. Then the coniform glan was reconstructed.

RESULTSFrom January 2008 to December 2013, 28 cases were treated, including glandular hypospadias, postoperative retraction of external urethral meatus and meatal stenosis. 21 patients were followed up for 1 -12 months (average, 1 month) with marked improvement of glan appearance and retraction of external meatus. No meatal stenosis happened.

CONCLUSIONSPostoperative retraction of urethral external meatus and meatal stenosis can be corrected by V shape flap on the dorsal side of glan combined with the bilateral glan flaps. The flat appearance of glan can be improved. It is an ideal method for glandular hypospadias.

Humans ; Hypospadias ; surgery ; Male ; Penis ; surgery ; Postoperative Complications ; surgery ; Postoperative Period ; Surgical Flaps ; Urethra ; surgery ; Urethral Stricture ; etiology ; surgery