Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance, making them an invaluable asset in the era of antibiotic resistance. Numerous depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models. Additionally, some formulation approaches have been developed for improved stability and activity of depolymerases. However, depolymerase formulation is limited to liquid dosage form and remains in its infancy, posing a significant hurdle to their clinical translation, compounded by challenges in their applicability and manufacturing. Future development must address these obstacles for clinical utility. Here, after unravelling the history, diversity, and therapeutic use of depolymerases, we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases. Finally, the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

Background Some studies have found that exposure to heavy metals significantly increases the risk of nonalcoholic fatty liver disease (NAFLD), and welding operators in automobile manufacturing enterprises are exposed to heavy metals in the working environment. Objective To analyze the prevalence and related factors of NAFLD in workers of an automobile company in Guangzhou. Methods From January 1 of 2023 to December 31 of 2023, 5463 workers of an automobile company in Guangzhou who participated in the physical examination in the Occupational Health Surveillance Centre of Guangzhou Occupational Disease Prevention and Treatment Hospital were selected as research subjects. The general data, laboratory examinations, B-ultrasound examinations, and other data of the subjects were obtained through the physical examination system. The exposed occupational hazards were identified based on the workplace hazard surveillance report provided by the automotive company. Logistic regression was used to analyze potential influencing factors of NAFLD, and stratified analysis was used to adjust confounding factors according to the stepwise model to evaluate the relationship between exposure to manganese and its inorganic compounds and NAFLD. Results A total of 2129 cases (38.97%) were reported positive NAFLD. The results of logistic regression analysis showed that women had a lower risk of NAFLD (OR=0.40, 95%CI: 0.25, 0.64), while age > 25 years old (OR=1.49, 95%CI: 1.39, 1.60), body mass index (BMI) ≥24 kg·m⁻² (OR=7.54, 95%CI: 6.46, 8.79), and elevated alanine aminotransferase (ALT) (OR=4.87, 95%CI: 3.73, 6.36), γ-glutamyl transpeptidase (γ-GGT) (OR=1.54, 95%CI: 1.17, 2.02), triglyceride (TG) (OR=3.47, 95%CI: 2.92, 4.14), and fasting blood glucose (OR=1.70, 95%CI: 1.32, 2.20) associated with a higher risk of NAFLD. NAFLD was positive in 39.40% of heavy metal exposed workers (701/1779). NAFLD was positive in 45.19% of workers exposed to manganese and its inorganic compounds (169/374), and among workers over 34 years old, exposure to manganese and its inorganic compounds (OR=1.79, 95%CI: 1.07, 2.97) significantly increased the prevalence of NAFLD. Conclusion The association between heavy metal exposure and NAFLD in workers of an automobile enterprise in Guangzhou is not significant, but age and gender are related to the prevalence of NAFLD. BMI, ALT, γ-GGT, TG, and fasting blood glucose are positively correlated with the prevalence of NAFLD. Exposure to manganese and its inorganic compounds in welding workers of the automobile enterprise is associated with elevated risk of the disease, and the prevalence of NAFLD is significantly increased in workers over 34 years old.

In this study,a functionalized covalent-organic framework(COF)was first synthesized using porphyrin as the fabrication unit and showed an edge-curled,petal-like and well-ordered structure.The synthesized COF was then introduced to prepare porous organic polymer monolithic materials(POPMs).Two com-posite POPM/COF monolithic materials with rod shapes,referred to as sorbent A and sorbent B,were prepared in stainless steel tubes using different monomers.Sorbents A and B exhibited relatively uniform porous structures and enhanced specific surface areas of 153.14 m2/g and 80.01 m2/g,respectively.The prepared composite monoliths were used as in-tube solid-phase extraction(SPE)sorbents combined with HPLC for the on-line extraction and quantitative analytical systems.Indole alkaloids(from Catharanthus roseus G.Don and Uncaria rhynchophylla(Miq.)Miq.Ex Havil.)contained in mouse plasma were extracted and quantitatively analyzed using the online system.The two composite multifunctional monoliths showed excellent clean-up ability for complex biological matrices,as well as superior selec-tivity for target indole alkaloids.Method validation showed that the RSD values of the repeatability(n=6)were≤3.46％,and the accuracy expressed by the spiked recoveries was in the ranges of 99.38％-100.91％and 96.39％-103.50％for vinca alkaloids and Uncaria alkaloids,respectively.Furthermore,sorbents A and B exhibited strong reusability,with RSD values≤5.32％,which were based on the peak area of the corresponding alkaloids with more than 100 injections.These results indicate that the composite POPM/COF rod-shaped monoliths are promising media as SPE sorbents for extracting trace compounds in complex biological samples.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective: To understand the current situation and associated factors of unintentional injury among preschool children in Shunyi District, and to provide reference for the development of unintentional injury intervention measures. Methods: Three kindergartens in Shunyi district were selected through stratified cluster sampling method, and all the parents were surveyed online by self-designed questionnaire. Results: The proportion of low, medium and high risk assessment of unintentional injury in preschool children were 59.5%, 37.5% and 3.0%, respectively. Risk of unintentional injury increased significantly with age and grade(χ 2=12.35, 12.70, P<0.05). The risk of unintentional injury in inter-generational care (3.7%) was higher than that in parental care(2.4%). The higher the education level of the primary caretaker and family income, the higher level of unintentional injury risk(χ 2=11.23, 14.10, P<0.05).There were significant differences in the risk for burning, poisoning, other accidental injury, prevention of accidental injury and total score of unintentional injury among children of different ages and classes(F=8.26，5.61，4.95，6.15，7.86；9.88，8.39，4.25，6.27，7.55，P<0.05). There was statistical significance in burning risk between boys and girls(t=-4.27, P<0.05). There was statistical significance in unintentional injury prevention between children of different residence(t=9.11, P<0.05). There were significant differences in behavior supervision among risk among children of different ages and grades(P<0.05). Multiple linear regression analysis showed that education level of primary caregivers (college:B=-2.66, 95%CI=-4.69--0.63; bachelor degree or higher:B=-3.80, 95%CI=-5.90--1.70), annual family income (B=-2.82, 95%CI=-4.80--0.84) were associated with unintentional injury risk of preschool children(P<0.05). Conclusion Health education of unintentional injury prevention among preschool children should focus on the primary caretaker with low education and low family income, which is crucial for prevention of children s injury.

[Abstract] Objective: To investigate the efficacy and safety of apatinib monotherapy in the treatment for patients with advanced colorectal cancer (CRC) who failed standard regimen. Methods: The required sample size in this prospective study was calculated with the PASS 15 software. A total of 52 patients with advanced colorectal cancer who failed standard regimen from July 2017 to August 2018 were included in this study. The patients were given apatinib monotherapy with an initial dosage of 750 mg or 500 mg. The objective remission rate (ORR) and disease control rate (DCR) were evaluated; the patients were followed up and progression-free survival (PFS) and overall survival (OS) were evaluated, and adverse events during treatment were recorded. The primary endpoint of this study was PFS, and secondary endpoints were ORR, DCR, OS and safety. Result: Of the 52 patients included, 45 patients, all of whom were late stage CRC patients with at least two systematic chemotherapeutic treatments, were available for efficacy evaluation. Treatment efficacy evaluation showed complete response of 0 case, partial response of 5 cases, stable disease of 30 cases and progression disease of 10 cases; the ORR was 11.11%, and the DCR was 77.78%. The prognosis data indicated that the median PFS of the 45 CRC patients was 3.95 months (95% CI=3.16-4.74), and the median OS was 10.3 months (95% CI=5.70-14.90). In terms of adverse events evaluation, the adverse reactions with grade 3 or above were hand-foot syndrome (6 cases, 13.33%), hypertension (5 cases, 11.11%), proteinuria (3 cases, 6.67%), diarrhea (3 cases, 6.67%), fatigue (2 cases, 4.44%) and bleeding (1 case, 2.22%). Conclusion: Apatinib monotherapy for patients with advanced colorectal cancer, who failed the standard regimens, has potential clinical benefits, and the overall toxicity profile is manageable.

[Abstract] Objective: To investigate the influence of glutathione S-transferase P-1 (GSTP1) genetic variation on the recurrence risk and prognosis of colorectal cancer (CRC) patients received postoperative adjuvant chemotherapy. Methods: The clinical data of 195 CRC patients, who received postoperative adjuvant chemotherapy in the Department of Gastroenterology of the FirstAffiliated Hospital of Zhengzhou University from January 2010 to December 2018, were collected for this study. 5-fluorouracil (5-FU) based adjuvant chemotherapy was given after surgical resection. The recurrence status of the patients was assessed during hospitalization period, and the long-term survival data of patients were obtained by telephone follow-up after finishing the scheduled adjuvant chemotherapy. GSTP1 genotyping was performed with the DNA extracted from peripheral blood specimens, and its correlation with patients’clinical characteristics wasanalyzed.Additionally, RNAwasextractedfrom peripheral blood mononuclear cell (PBMC) specimens of some CRC patients that prior to chemotherapy for GSTP1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and adjusted by multivariate Cox regression model. Results: The median disease-free survival (DFS) of the 195 CRC patients was 4.8 years, and the median overall survival (OS) was 6.2 years. Polymorphism analysis indicated that the I105VlocusofGSTP-1coding region was correlated with prognosis. The prevalence of I105V in the study population: AA genotype of 135 cases (69.23%), AG genotype of 56 cases (28.72%) and GG genotype of 4 cases (2.05%), the minor allele frequency of I105V was 0.16. The genotype distribution was in accordance with Hardy-Weinberg equilibrium (P>0.05). The analysis of recurrence risk and prognosis found that the median DFS of patients with AA genotype and AG/GG genotype was 5.7 and 3.9 years respectively (P<0.01), while the median OS of two groups of patients was 7.0 and 4.5 years respectively (P<0.01). The multivariate Cox regression results indicated that AG/GG genotype was an independent factor for OS (OR=1.54, P<0.05). The mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes were significantly higher than those patients with AA genotype (P<0.01). Conclusion: GSTP1 I105V genetic variation influences the recurrence risk and prognosis of CRC patients received postoperative adjuvant chemotherapy possibly via mediating the mRNAexpression of GSTP1.

Objective: To understand the epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in recent 5 years, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures. Methods: The two stage sampling method was used to survey 3 junior middle school schools randomly selected from Shunyi District, Beijing, in November 2013, December 2015 and November 2017. The number of students surveyed each year was 1 520, 1 404 and 1 467 respectively. Results: A total of 4 500 questionnaires were distributed and 4 391 questionnaires were valid, with an effective rate of 97.6%. The current smoking rate and the attempting smoking rate in Shunyi District junior high school students increased substantially, the difference was statistically significant(χ2=9.15, 11.54, P<0.01). The exposure rate of second-hand smoke among junior high school students in Shunyi District is increasing year by year. The current smoking rate and the attempting smoking rate of second-hand smoke at home and in public places were higher than those of non-exposed ones. The differences in the current smoking rates of junior high school students (χ2=25.86, 37.61, P<0.01) and the attempting smoking rate (χ2=49.51, 63-86, P<0.01) were statistically significant. The influence of Shunyi District junior high school students through different tobacco information access channels on the current smoking rate of junior high school students increased year by year. Different tobacco information access channels have significant difference in the influence of the junior middle school students’ attempting smoking rate(P<0.05). Conclusion The overall tobacco use of junior high school students in Shunyi District of Beijing is increasing by year. The exposure of second-hand smoke is not optimistic, and the supervision of tobacco information acquisition channels is urgent to be strengthened.

Objective To systemically review andquantify the incidence of oral feeding intolerance in acute pancreatitis. Methods Randomized controlled trials that reported the oral feeding intolerance rates of acute pancreatitis were searchedfrom PubMed, EMBASE, Medline, Cochrane Library, WanFang, CNKI, CMCC and VIP dal,abase wilh the" Acute pancreatitis " " Feeding intolerance" " Incidence" " Meta- analysis "from January 2002 to May 2017. Date were analyzed by using R 3. 4. 0 software. The heterogeneity of data were analyzed using 12test. Results Eleven randomized controlled trials including 658 cases were enrolled in Meta-analysis. The incidence of oral feeding of intolerance was 12. 2% . The result of subgroup analysis showed that there were no significant difference in the incidence of oral feeding intolerance when region, sample size and published year were taken into analysis (P > 0. 05). The oral feeding intolerance rate of mild acute pancreatitis was lower than that when moderately severe acute pancreatitis and severe acute pancreatitis were, included (8. 2% and 19. 9% , respectively; P = 0. 002 7). Conclusion Oral feeding intolerance affects approximately l in 8 patients with acute pancreatitis. The incidence of oral feeding intolerance of patients with severe acute pancreatitis is higher than that of patients with mild acute pancreatitis

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53(rAdp53) injection combined with radiotherapy and hyperthermia in the treatment of unresectable advanced soft tissue sarcoma.Methods In this retrospective study, we evaluated 76 patients with unresectable advanced primary or recurrent soft tissue sarcoma treated in our hospital from November 2005 to November 2012.These patients received radiotherapy and hyperthermia with rAdp53(p53 group, n=41) or without rAdp53(control group, n=35).rAdp53((1-2)×1012viral particles each time, once a week, 8 times on average) was injected into the tumor or infused into the pelvic cavity.Radiotherapy (2 Gy each time, 5 times a week) was performed for the planning target volume at 56.3±5.3 Gy in the p53 group and 58.1±4.2 Gy in the control group, with no significant difference between the two groups (P>0.05).Superficial or deep thermotherapy was employed 8 times on average (twice a week).Clinical features, response rate, time to progression (TTP), overall survival (OS), and adverse events were compared between the two groups (P>0.05).The Kaplan-Meier method was used to calculate OS;the log-rank test was used for survival difference analysis and univariate prognostic analysis;the chi-square test was used for comparison of categorical data.Results At 2 months after treatment, the p53 group had significantly increased response rate (partial response+ complete response+ stable disease)(85% vs.54%, P=0.003) and local control rate (49% vs.23%, P=0.020) as well as prolonged TTP (12 months vs.5 months, P=0.010) and OS (48 months vs.31 months, P=0.049), as compared with the control group.No adverse events caused by radiotherapy and hyperthermia except transient fever were seen in the two groups.Conclusions Concurrent radiotherapy and hyperthermia combined with rAdp53 injection is effective and safe for patients with advanced soft tissue sarcoma.