【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the molecular epidemiological characteristics of coxsackievirus A16 (CVA16) in Fujian province from 2020 to 2023.Methods:The epidemiological characteristics of CVA16 associated hand, food and mouth disease (HFMD) in Fujian province from 2020 to 2023 was analyzed. The complete VP1 gene of CVA16 was amplified by RT-PCR and then sequenced, and genetic evolution was analyzed by MEGA X and other softwares.Results:From 2020 to 2023, there were 13 120 cases of HFMD in Fujian province, and the proportion of HFMD which caused by CVA16 was 16.5% (2 160/13 120). From 2020 to 2023, the proportion of accounted cases was 4.7% (94/2 019), 14.1% (457/3 243), 47.6% (1 521/3 199) and 1.9% (88/4 659) respectively. HFMD caused by CVA16 was mainly concentrated in children aged 1 to 5 years, and most of them were 3 years old. The genetic evolution and genotype analysis of 92 complete VP1 gene sequences obtained from 2020 to 2023 showed that the genetic distance between CVA16 strains in Fujian province and the prototype strain was far away. The CVA16 genotype in Fujian province from 2020 to 2023 has three clusters of B1a, B1b and B1c, among which the composition ratio of B1a and B1b in Fujian province in 2020 was 40% and 60% respectively. In 2021, B1a and B1b accounted for 81.8% and 18.2% respectively. Only B1a in 2022; in 2023, there were B1a, B1b and B1c, which respectively accounted for 44.4%, 7.4% and 48.2%. During the period from January to September, B1a was the main cluster. After October we observed an emergence of B1c cluster, which had never been found in Fujian province and was rare in China, was detected and became the dominant cluster.Conclusions:The evolutionary cluster of CVA16 dominant changed from B1b in 2020 to B1a in 2021-2023. After October 2023, the newly discovered B1c became the dominant cluster in Fujian province.

With the increasing maturity of laparoscopic surgery, laparoscopic radical resec-tion of colorectal cancer has been widely used in colorectal surgery. Accurate localization of colorectal tumors and surgical margins in the absence of tactile sensation during surgery, ensuring sufficient blood flow perfusion at the anastomotic site and effectively reducing the incidence of anastomotic leakage have become barriers to the development of laparoscopic radical resection of colorectal cancer. The application of indocyanine green fluorescence imaging (ICG-FI) technology is expected to provide feasible solutions to the above-mentioned problems. Through this technology, accurate localization of colorectal tumors, evaluation of blood supply to the anastomotic site, lymphatic system imaging, detection of colorectal liver metastases, and protection of pelvic autonomous nerves and ureters can be achieved during laparoscopic surgery, thereby further improving the surgical quality of laparoscopic radical resection of colorectal cancer. However, the clinical application of ICG-FI technology in colorectal surgery is relatively short, which is still in the stage of exploration and experience accumulation, and there are few guideline or consensus available for reference. Therefore, the authors aim to provide a reference for the clinical application of this technology by reviewing and summarizing relevant literature based on different application types of ICG in colo-rectal cancer surgery.

Osteoarthritis(OA)is the most common degenerative disease in clinical practice.Joint pain is the main manifestation of OA,and in severe cases,it can lead to joint deformity.The main pathological changes include destruction of articular cartilage,synovitis,thickening of subchondral bone,bone redundancy,degeneration of articular ligaments,and enlargement of articular periosteum.Clinicopathological changes and pain degrees in OA patients vary from person to person,and treatment options vary from person to person.Clinically,non-steroidal anti-inflammatory drugs are used to treat the pain of OA patients now,but the effect is not ideal,and long-term use of these drugs will bring obvious toxic and side effects.Traditional Chinese medicine obtains good results in relieving the pain of OA patients.Therefore,this paper reviews the research on traditional Chinese medicine treatment and pain mechanisms of OA,with a view to providing ideas and references for clinical relief of pain in OA patients.

OBJECTIVE To optimize the processing technology of honey bran-fried Atractylodis Rhizoma， and to compare the anti-gastric ulcer effect before and after processing. METHODS Combing with entropy-weight and technique for order preference by similarity to ideal solution model， L（9 34） orthogonal experiment design was adopted to optimize the processing technology of honey bran-fried Atractylodis Rhizoma using the comprehensive score of the contents of atractylone， β-cineole， atractylenolide Ⅲ and atractylodine as evaluation index， using the ratio of excipients to medicine， frying temperature and frying time as factors. The validation tests were conducted. The gastric ulcer model of mice was induced by intragastrical administration of anhydrous ethanol； using Compound aluminum hydroxide tablet as positive control， anti-gastric ulcer effect of Atractylodis Rhizoma was compared with that of honey bran-fried Atractylodis Rhizoma using the contents of serum inflammatory factors [interleukin-2 （IL-2）， IL-6， tumor necrosis factor-α （TNF-α）]， ulcer index and inhibitory rate of gastric ulcer as evaluation indexes. RESULTS The optimal processing technology of honey bran-fried Atractylodis Rhizoma was as follows：ratio of adjuvant and medicinal materials of 3∶10 （g/g）， frying temperature at 140 ℃ and frying time of 4 min. Results of 3 validation tests showed that the contents of 4 components （including atractylone）， in honey bran-fried Atractylodis Rhizoma processed by the optimal technology kept stable （RSDs were 3.47%-5.80%， n＝3）； the comprehensive scores were 95.53%-95.89% （RSD＝0.21%， n＝3）. Atractylodis Rhizoma and honey bran-fried Atractylodis Rhizoma could increase the serum content of IL-2 in mice， but reduce serum contents of IL-6 and TNF-α to varying degrees； honey bran-fried Atractylodis Rhizoma could significantly decrease its ulcer indexes （P＜0.05 or P＜ 0.01）； the improvement effect of honey bran-fried Atractylodis Rhizoma on the above indicators was generally better than that of the same dosage of Atractylodis Rhizoma （P＜0.05 or P＜ 0.01）. The inhibitory rates of low-dose， medium-dose and high-dose Atractylodis Rhizoma and honey bran-fried Atractylodis Rhizoma to gastric ulcer in mice were 9.18%， 19.30%， 30.70%， and 50.32%， 61.39%， 53.16%， respectively. CONCLUSIONS The optimal processing technology of honey bran-fried Atractylodis Rhizoma is stable and feasible， and the anti-gastric ulcer effect of Atractylodis Rhizoma has been enhanced after being fried with honey bran.

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4⁺ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4⁺ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4⁺ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/10⁶ CD4⁺ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Purpose: This study was performed to investigate the association of Glasgow prognostic score (GPS), combined positive score (CPS), and clinicopathological characteristics of locally advanced rectal cancer. Methods: Between February 2012 and February 2018, 103 patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy and total mesorectal excision (TME) were retrospectively evaluated. Results: According to the classification of the GPS, 85 (82.5%), 13 (12.6%), and 5 patients (4.9%) were classified as a score of 0, 1, and 2, respectively. Patients were classified into the GPS-low group (GPS of 0, n = 85) and GPS-high group (GPS of 1 or 2, n = 18) with an area under the curve of 0.582 for overall survival (OS). The mean programmed death-ligand 1 (PD-L1) CPS of the whole group was 2.24 (range, 0–70). The PD-L1 CPS of the GPS-high group was higher than the GPS-low group (P < 0.001). Multivariate analysis by Cox proportional hazards model indicated that GPS was associated with OS and diseasefree survival (DFS). Furthermore, PD-L1 CPS was associated with DFS (hazard ratio, 1.050; 95% confidence interval, 1.017– 1.083; P = 0.003). Conclusion Elevated GPS was related to the PD-L1 CPS. GPS and PD-L1 CPS were associated with the prognosis of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by TME.

Objective:To investigate abnormal urination and penile appearance satisfaction of preschool children (3-6 years old) after hypospadias repair.Methods:From January 2016 to December 2020, children with primary hypospadias, who had no postoperative complications for more than 1 year and were at pre-school age at the time of investigation (January 2022), were selected. The abnormal urination manifestations and satisfaction with penile appearance of the children after operation were investigated by questionnaires to their parents.The questionnaire was designed based on the reported abnormal urination after hypospadias surgery, including 4 items (urination spraying, urination dripping, deflection of urine line, small urine line). Another questionnaire was used to evaluate the penis appearance satisfaction according to the existing pediatric penile perception score (including 4 items: the position and shape of the external urethral orifice, the shape of glans, the appearance of the prepuce, and the overall appearance; items were scored according to the subjective satisfaction of the subjects: very satisfied 3 points, satisfied 2 points, dissatisfied 1 point, very dissatisfied 0 point). The patients were divided into two groups according to whether the penile curvature after degloving was more than 30°. In group Ⅰ (penile curvature≤30°), 28 patients without severe penile curvature underwent tubularized incised plate (TIP) surgery, with a median age of 3.2 years (ranged 1.1-5.4 years). In group Ⅱ (penile curvature>30°), there were 27 patients with severe penile curvature and they underwent staged flap operation. Their median age was 2.8 years (ranged 1.5-4.7 years). There was no significant difference in age at operation between the two groups ( P=0.82). The questionnaire content was analyzed and the differences between the two groups were compared. Results:Among the 55 children, 21(38%, 21/55) had abnormal urination, and there was a significant difference between group Ⅰ (25%, 7/28) and group Ⅱ (52%, 14/27)( P=0.04). All the items of penis appearance satisfaction were satisfactory (scores ≥2), and the total scores of group Ⅰ and group Ⅱ were respectively 10.3±2.2 and 9.0±2.9, with no significant difference between the two groups (P=0.63). Conclusions:In the postoperative follow-up of preschool children with hypospadias, parents were satisfied with the appearance of the penis.The abnormal urination was common. Compared with children without severe penile curvature treated by TIP surgery, abnormal urination was more common in children with severe penile curvature treated by staged flap operation.