Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective: To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies. Methods: Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed. Results: A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05). Conclusions The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Humans ; Neoplasms/pathology* ; Immunotherapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To investigate the self-healing of congenital auricular deformity (CAD) and the efficacy of the auricle corrector in infants.Methods:The infants with CAD who were born in the Affiliated Maternity and Child Health Care Hospital of Nantong University from January to December 2020 were collected. The patients who disagreed with the use of auricle corrector were included in the observation group. The patients were followed up on the day of one month and one year after birth by phone or WeChat, and the self-healing rate (the proportion of the number of ears found to be healed in the total number of affected ears after follow-up) of auricle was calculated. The patients treated with auricle corrector were included in the non-invasive correction group, which was treated with domestic auricle corrector. And according to the initial correction age, the patients were divided into ≤7 d, 8-28 d and >28 d three subgroups. The patients were followed up on the day of one month and one year after treatment by phone or WeChat, and the effective rate(the proportion of healed ears to the total number of affected ears after treatment) was calculated. And statistical analysis was used in the three subgroups of initial correction age ≤7 d, 8-28 d, >28 d. Variance analysis was used for general comparison between three groups, and LSD- t test for the comparison between two groups. P<0.05 was considered statistically significant. Results:A total of 43 children (71 ears, 34 left ears and 37 right ears) were included in the observation group, including 21 males and 22 females, (2.1±0.3) days after birth. In the non-invasive correction group, 24 children (41 ears, 20 left ears and 21 right ears) were included, including 8 males and 16 females, (29.1±23.8) days after birth. There were 6 cases (10 ears) in the initial correction age group ≤7 days, 6 cases (9 ears) in the 8-28 days group, and 12 cases (22 ears) in the >28 days group. In the observation group (71 ears), the rates of self-healing on the day of one month and one year after birth were 29/71 and 30/71, respectively, including 23/31 and 24/31 for lop ear, 3/6 for Stahl’s ear, 3/3 for complex deformity, and 0 for other ear deformities. The effective rates were 41/41 and 35/41 one month and one year after treatment in the 24 children (41 ears) in the non-invasive correction group, respectively. Among them, the helical rim deformity was 12/12, lop ear 3/3, cup ear 7/7 and 5/7, Stahl’s ear 4/4, contracted ear 6/6, 5/6, prominent ear 2/2 and 0, the complex deformity 6/6 and 5/6, and microtia(Ⅰ) 1/1. The auricular deformities reoccurred in a total of 4 children (6 ears) 1 year after the end of treatment. According to the initial correction age into three groups, the treatment duration of the auricle corrector was (31.8±11.2) days, (31.3±10.1) days and (41.8±13.8) days, and the difference among the three groups was statistically significant ( F=3.42, P=0.043). There was no statistical significance between the groups ≤7 days and 8-28 days ( P=0.936), but there was statistical significance in the treatment duration between the groups ≤7 days and >28 days ( P=0.043), and between the groups 8-28 days and > 28 days ( P=0.041). Conclusion:CAD can self-heal to some extent. Self-healing rate is higher in lop ear and Stahl’s ears. The domestic auricle corrector has a good effect on CAD. The older the age of initial correction is, the longer the time of correction is. The type of CAD has a certain influence on the correction effect.

Objective:To investigate the self-healing of congenital auricular deformity (CAD) and the efficacy of the auricle corrector in infants.Methods:The infants with CAD who were born in the Affiliated Maternity and Child Health Care Hospital of Nantong University from January to December 2020 were collected. The patients who disagreed with the use of auricle corrector were included in the observation group. The patients were followed up on the day of one month and one year after birth by phone or WeChat, and the self-healing rate (the proportion of the number of ears found to be healed in the total number of affected ears after follow-up) of auricle was calculated. The patients treated with auricle corrector were included in the non-invasive correction group, which was treated with domestic auricle corrector. And according to the initial correction age, the patients were divided into ≤7 d, 8-28 d and >28 d three subgroups. The patients were followed up on the day of one month and one year after treatment by phone or WeChat, and the effective rate(the proportion of healed ears to the total number of affected ears after treatment) was calculated. And statistical analysis was used in the three subgroups of initial correction age ≤7 d, 8-28 d, >28 d. Variance analysis was used for general comparison between three groups, and LSD- t test for the comparison between two groups. P<0.05 was considered statistically significant. Results:A total of 43 children (71 ears, 34 left ears and 37 right ears) were included in the observation group, including 21 males and 22 females, (2.1±0.3) days after birth. In the non-invasive correction group, 24 children (41 ears, 20 left ears and 21 right ears) were included, including 8 males and 16 females, (29.1±23.8) days after birth. There were 6 cases (10 ears) in the initial correction age group ≤7 days, 6 cases (9 ears) in the 8-28 days group, and 12 cases (22 ears) in the >28 days group. In the observation group (71 ears), the rates of self-healing on the day of one month and one year after birth were 29/71 and 30/71, respectively, including 23/31 and 24/31 for lop ear, 3/6 for Stahl’s ear, 3/3 for complex deformity, and 0 for other ear deformities. The effective rates were 41/41 and 35/41 one month and one year after treatment in the 24 children (41 ears) in the non-invasive correction group, respectively. Among them, the helical rim deformity was 12/12, lop ear 3/3, cup ear 7/7 and 5/7, Stahl’s ear 4/4, contracted ear 6/6, 5/6, prominent ear 2/2 and 0, the complex deformity 6/6 and 5/6, and microtia(Ⅰ) 1/1. The auricular deformities reoccurred in a total of 4 children (6 ears) 1 year after the end of treatment. According to the initial correction age into three groups, the treatment duration of the auricle corrector was (31.8±11.2) days, (31.3±10.1) days and (41.8±13.8) days, and the difference among the three groups was statistically significant ( F=3.42, P=0.043). There was no statistical significance between the groups ≤7 days and 8-28 days ( P=0.936), but there was statistical significance in the treatment duration between the groups ≤7 days and >28 days ( P=0.043), and between the groups 8-28 days and > 28 days ( P=0.041). Conclusion:CAD can self-heal to some extent. Self-healing rate is higher in lop ear and Stahl’s ears. The domestic auricle corrector has a good effect on CAD. The older the age of initial correction is, the longer the time of correction is. The type of CAD has a certain influence on the correction effect.

Objective: To study on the difference of serum iron(Fe) levels between normal healthy people and patients with AD in order to explore the effect of serum iron level on the phenotypical division of AD patients and discuss its influence and significance in the diet nursing of AD patients. Methods: A total of 30 patients with AD in Guangzhou Huiai Hospital were selected as the "AD group" from June 2014 to August 2017, and 30 healthy people in the corresponding health center of Guangzhou Huiai Hospital were selected as "the health control group". Data of general information, serum iron and red blood cell(RBC) index were collected in these two groups. General statistical analysis and cluster analysis were made based on the data. Results: RBC in healthy control group and AD group were 4.60(4.38,5.00)×10¹²/L and (4.32±0.51)×10¹²/L. Compared with the healthy control group, RBC in the AD group was lower and the difference was statistically significant (Z=2.493, P<0.05). But, the other indexes were not significantly different (P>0.05). There was no significant difference in the in Fe level, RBC, hemoglobin and other indexes in AD patients with the different severity of dementia (P>0.05). Based on the level of Fe and RBC, the 60 cases can be divided into four types of different characteristics.The Fe of four types were (12.39±2.35) , (13.55±2.07) ,[20.70(19.55,23.15)], [19.70(17.70,22.60)] μmol/L, the RBC were (4.07±0.30), [4.83(4.62,5.12)], [4.40(4.14,4.45)], [5.00(4.80,5.34)]×10¹²/L. The HGB were (125.30±8.74), (138.08±11.1), [136.00(127.00,139.00)], (151.91±13.49)g/L.The incidence of four types of AD, Fe level, RBC and hemoglobin content were different (t/Z/χ²=0.019-6.942, P<0.05). Conclusions Based on Fe and RBC, the population can be divided into 4 types. "Low Fe and low RBC"Type, "High Fe and high RBC"Type, "Low Fe and high RBC"Type and"High Fe and low RBC"."Low Fe and low RBC"Type contains most AD patients while "High Fe and high RBC"Type contains the least. There are close in the distribution of objects between"Low Fe and high RBC" and "High Fe and low RBC". According to the characteristics of these four types, different dietary care programs may be required

Objective To study the effects of different sources of dendritic cells (DCs) on root resorption and healing after allo-geneic tooth transplantation in rats .Methods The BN rats and Lewis rats were respectively used as the donor and recipient teeth for establishing the animal experimental transplantation models and randomly divided into 4 groups ,20 cases in each group :the syn-geneic transplantation group(A) and the allogeneic transplantation groups(B ,C ,D) .The group A and B were infused with PBS buffer solution 0 .5 mL on 7 d before operation .The group C and D were infused with 1 × 106 donor or recipient tolerogenic DCs on 7 d before operation .5 rats randomly selected from each group were sacrificed for performing the pathological examinations of transplanted teeth at the end of 1 ,2 ,4 and 8 weeks .Results The inflammatory cellular infiltration was most severe in the group B , slightest in the group A and moderate in the group C and D .The root resorption was minimal in the group A ,maximal in the group B and moderate in the group C and D (P<0 .05);the root resorption at 2 ,4 weeks had no statistical difference between the group C and D(P>0 .05) ,but which at 8 weeks in the group D was lower than that in the group C .The periodontal membrane healing points at 8 weeks in the group C and D was less than that in the group A ,but more than that in the group B (P<0 .05);the inflam-matory absorption was highest in the group B(P<0 .05);the alternative absorption was lowest in the group A (P<0 .05) .Conclu-sion The two different sources of tolerogenic DCs all could reduce the rejection reaction of allogeneic tooth transplantation ,reduce the root resorption and promote the healing of periodontal membrane .Recipient tolerogenic DCs could reduce the root resorption in late stage even more .

Objective To investigate the effect of intracerebroventricular injection of morphine and orphanin FQ (OFQ) on somatosensory evoked potential (SEP) and Na+-K+ATPase activity in cerebral cortex of rat. MethodsTo study the SEP with the BL-420 biological signal collecting system. The cerebral cortex tissues were extracted, homogenized and centrifuged. Na+-K+ATPase activity was measured with ATPase analytical kit. Results After intracerebroventricular injection with OFQ 0.9 ?g, the amplitude of P1-N1 and N1-P2 increased significantly(P

Atlas fracture is a rare lesion occurred in cervical vertebrae.This review summarize the new approach about the classification,etiological factors,clinical manifestations,diagnosis methods and treatments of the disease.