Objective To prepare a dissolvable microneedle(MN)patch loaded with sodium houttuyfonate(SH)combined with erythromycin(ERY)(SH+ERY-MN patch),to characterize its properties,and to investigate its synergistic anti-acne effects and the mechanisms involved.Methods The SH+ERY-MN patch was prepared by two-step centrifugation.The morphology and skin puncture performance of the microneedles were evaluated using scanning electron microscopy,puncture tests,and other methods.The combined antibacterial effect was assessed using the checkerboard assay.The in vitro anti-inflammatory effect of the SH+ERY-MN patch was evaluated by quantitative PCR(qPCR)and enzyme-linked immunosorbent assay(ELISA).The therapeutic effect of the SH+ERY-MN patch on acnes in mice was investigated using an animal model.Results The microneedle patch prepared in the study had well-aligned microneedles,excellent needle shape,and good mechanical properties,which could effectively penetrate the skin to reach the superficial dermis.The minimum inhibitory concentration(MIC)of ERY against acne was 1.28 mg/mL.When ERY was combined with SH,the results showed that the fractional inhibitory concentration(FIC)was 0.375,indicating that the medication combination had a synergistic antibacterial effect.In particular,the MIC value of ERY in combination was 1/4 of that of ERY used alone.The results of in vitro qPCR showed that SH+ERY-MN could downregulate the production of interleukin(IL)-1β,IL-18,tumor necrosis factor α(TNF-α),inhibitor of κB(I-κB),Toll-like receptor 4(TLR4),NLR family pyrin domain containing 3(NLRP3),and cysteine-aspartic proteases(Caspase-1)induced by Propionibacterium acnes(PA)in cell culture supernatant(P＜0.05).According to the in vivo findings,SH+ERY-MN had a significant anti-acne effect and effectively alleviated cytokine-mediated inflammatory responses.The results of qPCR and ELISA showed that SH+ERY-MN could effectively reduce the levels of IL-1β,IL-18,NLRP3,and Caspase-1 in the serum of the mouse acne inflammation model(P＜0.01),and had good antibacterial and anti-inflammatory effects.Conclusion SH+ERY-MN patch was successfully prepared and demonstrated obvious anti-acne effects.The SH+ERY-MN patch enhances the transdermal delivery of SH combined with ERY.It provides an innovative method for acne treatment and creates new possibilities for achieving effective drug delivery and improving therapeutic efficacy.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective　To explore the parainfluenza virus (PIV) infection in children hospitalized in Hainan between March 2012 and December 2022, and to analyze its epidemiological characteristics. Methods　The samples were obtained from 62 553 kids with respiratory infections who were hospitalized in the Department of Pediatrics of multiple hospitals in various regions of Hainan from March 2012 to December 2022. Indirect immunofluorescence was employed to detect IgM antibodies in serum for nine respiratory pathogens, including PIV, adenovirus, influenza A virus, Legionella pneumophila, respiratory syncytial virus, Mycoplasma pneumoniae, influenza B virus, Coxiella burnetii, and Chlamydia pneumoniae. Epidemiological and clinical data (time, gender, age, season, etc.) of PIV-IgM antibody-positive cases were analyzed in a descriptive study. Results　The total PIV-IgM antibody positive rate of 62 553 respiratory tract infected children was 3.29% (2 015/62 553), with the highest positive rate of 11.01% (385/3 496) in 2017, and the second highest positive rate of 8.37% (351/4 196) in 2016, which were significantly higher than the positive rate of the rest of the years (P<0.001). The PIV positive rate was 3.18% (1 248/39 225) in males and 3.29% (767/23 328) in females, with no statistically significant difference (P>0.05). PIV infection occurred in all age groups, with the highest positive rate in the 6 to <12 years group at 4.50% (357/7 941), followed by the 3 to <6 years group at 4.47% (656/14 689), significantly higher than other age groups (P<0.001). The highest positive rate for PIV was in summer at 4.30% (693/16 093), followed by 3.78% (598/15 804) in spring, and the lowest rate of 2.27% (342/15 065) in winter, with statistically significant differences (P<0.001). Single PIV infection accounted for 63.08% (1 271/2 015), while mixed infections accounted for 36.92% (744/2 015), and the most common co-infection being with Mycoplasma pneumoniae infection at 23.13% (466/2 015). Conclusions　PIV is an important pathogen for children's acute respiratory infections in Hainan Province, exhibiting year-round sporadic occurrence with alternating high and low periods characteristics. PIV infection is to the gender of the child, predominantly affects preschool and school-age children, peaks in spring and summer, and commonly co-infects with Mycoplasma pneumoniae infection.

Objective To evaluate the accuracy and reproducibility of AlignRT-guided positioning by comparing two positioning workflows for pelvic tumor radiotherapy,and to further explore the feasibility of using it to replace skin marker alignment.Methods Forty cases of pelvic tumor treated with radiotherapy using Infinity accelerator in Sun Yat-sen University Cancer Center between March 2022 and March 2023 were included in the study,with 20 cases using the skin marker alignment workflow and the other 20 adopting AlignRT-guided positioning workflow.The translational errors(LAT,LNG,VRT)and rotational errors(Yaw,Pitch,Roll)were determined by the registration of pre-treatment cone-beam CT(CBCT)with planned CT.Both CBCT shifts and error offset distributions were analyzed;planning target volume(PTV)margins were calculated;and correlation analyses were conducted among six-dimensional errors,and between body mass index and setup errors.Results The median translational and rotational setup errors of skin marker alignment workflow vs AlignRT-guided positioning workflow were 0.19-0.34 cm vs 0.10-0.15 cm and 0.50°-1.30°vs 0.50°-0.70°,with the maximum offset ranges of 1.20-1.70 cm vs 0.42-0.47 cm and 2.00°-5.50° vs 1.80°-2.00°,respectively.Additionally,for skin marker alignment workflow,inter-fractional errors>0.5 cm and>3° were observed in 23.3%and 9.8%of fractions.The PTV margins of AlignRT-guided positioning workflow were 0.37,0.38 and 0.34 cm in the left-right,superior-inferior and anterior-posterior directions,respectively,which were much smaller than those of skin marker alignment workflow(0.67,1.22 and 0.95 cm).No correlation was found between six-dimensional errors in two positioning workflows.When using AlignRT-guided positioning workflow,the setup errors in LAT,LNG and Pitch directions had low correlations with body mass index.Conclusion In pelvic tumor radiotherapy,AlignRT-guided positioning can reduce translational and rotational errors,achieve precise setup and excellent inter-fractional reproducibility and stability,and replace traditional skin marker alignment while being used in conjunction with CBCT.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective To analyze the status and risk factors of Helicobacter pylori (Hp) infection in permanent residents in a certain area. Methods The clinical data of 6 792 permanent residents surveyed from January 2021 to December 2023 were retrospectively analyzed. All subjects underwent 13C-urea breath test，and relevant general information was collected to analyze Hp infection status. According to whether Hp infection occurred, they were divided into positive group (n=4 283) and negative group (n=2 509). The differences in general information, living habits, and dietary habits between the two groups of subjects were analyzed, and multivariate logistic regression analysis was conducted. Results Among the 6 792 permanent residents surveyed from January 2021 to December 2023, 4283 were positive for 13C-urea breath test, accounting for 63.05% of the total. There were statistically significant differences in age distribution, gender, BMI, tableware cleaning, personal hygiene products use, chopsticks use, and raw food and vegetable cleaning between the positive group and the negative group (P<0.05). The single factors of Hp infection were substituted into multivariate logistic regression analysis equation, and it was found that age ≥45 years old, male, BMI≥24, no use of detergents to clean utensils, sharing personal hygiene products, not using public chopsticks, having a habit of eating raw food, and not cleaning vegetables before eating were independent risk factors for Hp infection. Conclusion The positive rate of Hp infection in this area is relatively high, and the infection factors are related to age, gender, and some lifestyle and dietary habits.