Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective To investigate the clinical characteristics of drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with hepatitis B virus (HBV). Methods A total of 133 patients with pulmonary tuberculosis and HBV who were treated in Zhuzhou Central Hospital from January 2018 to early January 2022 were selected, and all were treated with conventional anti-tuberculosis 2HRZE/4HR regimen. According to the liver injury, the patients were divided into liver injury group and no liver injury group. Univariate analysis was used to analyze the related factors of liver injury caused by anti-tuberculosis drugs, and multivariate logistic regression analysis was used to analyze the independent risk factors of liver injury caused by anti-tuberculosis drugs. Results Among 133 cases of newly treated pulmonary tuberculosis patients with HBV, 24 cases had liver injury caused by anti-tuberculosis drugs, accounting for 18.05%; 109 patients had no liver injury caused by anti-tuberculosis drugs, accounting for 81.95%. Univariate analysis showed that there were significant differences in smoking history, drinking history, diabetes history, hypertension history, anti-tuberculosis treatment plan, malnutrition, and use of hepatoprotective drugs between the liver injury group and the no liver injury group (P<0.05). Multivariate logistic regression analysis showed that smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs were independent risk factors for liver injury caused by anti-tuberculosis drugs. Conclusion Smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs are the risk factors for drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with HBV.

OBJECTIVE To systematically evaluate the efficacy and safety of oral Janus kinase （JAK） inhibitor in the treatment of alopecia areata （AA）in order to provide evidence -based reference for clinical use . METHODS PubMed，Embase， Web of Science ，the Cochrane Library ，CNKI，Wanfang and CBM were searched from the inception to March 29，2022. Randomized controlled trials （RCTs）of oral JAK inhibitors （trial group ）versus placebo （control group ）in the treatment of AA were collected . Two researchers independently screened the literature ，extracted the data ，and evaluated the quality of the included studies. RevMan 5.4 software was used for meta -analysis and analysis of publication bias . RESULTS A total of 2 170 patients were enrolled in 5 RCTs，including 1 619 in the trial group and 551 in the control group . Meta-analysis results showed that ：compared with control group ，the ratio of the patients with the Severity Alopecia Tool （SALT）score ≤20 at 24th week [RR＝6.10，95%CI （3.86，9.63），P＜0.000 01] and 36th week [RR＝6.59，95%CI（4.16，10.43），P＜0.000 01] were both higher ；Hospital Anxiety and Depression Scale -Anxiety （HADS-A） score [RR＝0.35， 95%CI （0.07，0.64），P＝0.02] and Hospital Anxiety and 1009） Depression Scale -Depression （HADS-D） score [RR＝0.50， 95%CI（0.22，0.77），P＝0.000 4] were more decreased at 24th week . HADS-A score [RR＝0.55，95%CI（0.21，0.89）， 话：0371-66913047。 P＝0.001] and HADS -D score [RR＝0.50， 95%CI （0.16，0.84），P＝0.004] were also significantly decreased at 36th week . The incidence of acne [RR＝4.07，95%CI（1.83，9.08），P＝0.000 6] and low density lipoprotein （LDL）elevation [RR＝1.66，95%CI（1.21，2.28），P＝0.002] in trial group were incr eased significantly （P＜0.05）. There were no significant differences in the incidence of urinary tract infection，upper respiratory tract infection ， headache，nasopharyngitis and creatine phosphokinase elevation between 2 groups （P＞0.05）. There was little possibility of publication bias in this study based on the publication bias analysis . CONCLUSIONS Oral JAK inhibitor can significantly improve AA patients ’hair regrowth ，anxiety and depression . Acne and LDL elevation are the main adverse events .

Objective:To analyze the articles and literature indicators of Cancer Research and Clinic, in order to provide reference for the development of the journal. Methods:All articles published in Cancer Research and Clinic from January 2017 to December 2021 were searched on the official website of the journal (www.zlyjylc.com.cn), and the core literature indicators of Cancer Research and Clinic published in the Citation Report of Chinese Science and Technology Journals (Core Edition) from 2018 to 2022 were searched, and the statistical analysis of the articles and literature indicators was performed using bibliometric method and Excel software. Results:From 2017 to 2021, a total of 60 issues of Cancer Research and Clinic were published, containing a total of 1 065 articles, with an average of 17.8 articles per issue; a total of 4 416 pages of articles were published, with an average of 4.1 pages per article. There were 609 original articles (57.2%), 193 brief communications (18.1%) and 224 reviews (21.0%) in the main sections. The degree of authorship cooperation was 3.84 (4 086/1 065). The first author affiliation of the article was located in 31 regions, of which the top 10 regions in terms of the number of articles published were Shanxi, Jiangsu, Beijing, Shandong, Hubei, Shaanxi, Liaoning, Guangdong, Henan, and Hebei, with a total of 822 articles (77.2%). A total of 487 articles (45.7%) were funded by the foundation, including 134 articles (12.6%) funded by the national foundations. The average number of citations per article was 19.3 (20 557/1 065); the total number of marked keywords was 4 412, with an average of 4.1 per article. The impact factor and total citation frequency in 2018 were the highest (0.680 and 775), and the rate cited, open factor and overall evaluation total score in 2021 were the highest (0.94, 42 and 29.8). Conclusions:Cancer Research and Clinic has adhered to its own purpose and formed its own characteristics, and its academic quality and influence have steadily improved in the field of oncology in China in recent years. It should continue to improve the quality and strive to be a first-class oncology journal in the future.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To analyze the situation of articles published in Journal of Leukemia & Lymphoma and provide reference for the development of the journal and better service to readers and authors. Methods:All articles published in Journal of Leukemia & Lymphoma from January 2019 to December 2021 were searched on the official website of the journal (www.bxblbl.com.cn) and the full-text database of Chinese medical journals (www.yiigle.com), and the statistical analysis of the articles published in the journal was performed using bibliometric methods and Excel software. Website readings and downloads were recorded based on data from the Chinese medical journal network publishing platform (https://app.yiigle.com/cmaapp/). Results:From January 2019 to December 2021, 36 issues of Journal of Leukemia & Lymphoma were published, containing a total of 578 articles, with an average of about 16 articles per issue. There were 222 (38.4%) original articles, 173 (29.9%) brief communications, 11 (1.9%) guidelines and consensus articles, 58 (10.0%) topic reviews, and 94 (16.3%) reviews; the degree of authorship cooperation was 5.10 (2 946/578). The first author's affiliation included 28 provinces, cities and autonomous regions. The top 10 regions were Jiangsu, Henan, Beijing, Fujian, Shanxi, Guangdong, Tianjin, Shanghai, Hebei, and Shandong, with a total of 425 (73.5%) articles. There were 257 (44.5%) funded articles, including 105 (18.2%) articles funded by national funds. The average number of citations per article was 18.6 (10 751/578). The average annual number of reads was 104 630, and the top 20 most-read articles in 2021 were mostly in the category of guidelines and consensus and topical reviews. Conclusions:Journal of Leukemia & Lymphoma has developed well in recent years, and its influence in the field of hematology-oncology has steadily increased. In the future, according to the purpose of the journal, the special columns should be further created, and the academic quality should be improved to better serve the readers and authors.

Human microbiota is composed of bacteria, viruses, fungi and other microorganisms, which are distributed in the oral cavity, nasal cavity, intestine, vagina and skin, etc. Human microbiota plays a pivotal role in the metabolism, immunity, hormones and homeostasis of the host. It can protect the host and maintain the homeostasis, and provoke the incidence of inflammation and tumors. Microbiota has been found to modulate the efficacy and toxicity of chemotherapy and immunotherapy for certain types of tumors. Nevertheless, large-scale studies in the context of radiation therapy have not been performed. In this article, the relationship between the microbiota and the radiotherapy response and toxicity changes of cancer patients was summarized, aiming to develop the optimal treatment plan for patients, and provide evidence for the prevention and treatment of radiotherapy-induced injury.

Objective:To investigate the distribution of pathogen species isolated from cerebrospinal fluid culture (CSF) in children and analyze the antibiotic-resistance of the main isolates in vitro, which provides reference for interpreting the pathogens and choosing antibiotics in empiric therapy for pediatric patients. Methods:The results of cerebrospinal fluid culture were collected by checking laboratory information system of the Children′s Hospital of Zhejiang University and the clinical characteristics of these children were analyzed retrospectively by checking electronic medical record system.Results:A total of 1 312 isolates were detected, including 1 294 isolates of bacteria and 18 isolates of fungi. A total of 497 (37.9%) isolates were pathogenic microorganisms, of which 288 (57.9%) isolates were gram-positive, 200 (40.3%) isolates were gram-negative, and 9 (1.8%) isolates were fungi. The top 5 pathogens were Escherichia coli (102 isolates, 20.5%), Streptococcus pneumoniae (64 isolates, 12.9%), Streptococcus agalactiae (52 isolates, 10.5%), Enterococcus faecium (33 isolates, 6.6%) and Staphylococcus aureus (28 isolates, 5.6%). Most of the Streptococcus pneumoniae strains were isolated from children more than 1 year old (76.6%, 49/64), while the other top 4 bacteria were mainly isolated from infants less than 1 year old, with the rate of 95.1%(97/102) for Escherichia coli, 98.1%(51/52) for Streptococcus agalactiae, 81.8%(27/33) for Enterococcus faecium and 71.4% (20/28) for Staphylococcus aureus. A total of 815 (62.1%) isolates were considered to be contaminated pathogens according to the analysis on clinical manifestations and other laboratory findings in CSF, and coagulase-negative Staphylococcus (680 isolates), Micrococcus (50 isolates), Corynebacterium (28 isolates) and Enterococcus faecium (23 isolates), which accounted for 41.1% (23/56) of the total detected Enterococcus faecium, were the top 4 contaminated bacteria. During the study period, the isolation rate of the pathogenic microorganisms increased year by year (χ2=34.84, P<0.001), while the isolation rate of the contaminated pathogens, which detected mainly in summer and autumn, decreased year by year (χ2=13.26, P<0.001). Conclusions:The predominant bacteria causing pediatric purulent meningitis were Escherichia coli, Streptococcus pneumoniae, Streptococcus agalactiae, Enterococcus faecium and Staphylococcus aureus. Coagulase-negative Staphylococcus, Micrococcus, Corynebacterium and Enterococcus faecium were common contaminated bacteria in CSF culture, therefore clinicians should interpret the results of CSF culture cautiously according to the bacterial species and clinical manifestations.

Objective:By comparing the clinical effect of minimally invasive hollow screw internal fixation Assisted by orthopedic robot (TiRobot) and O-arm navigation in the treatment of pelvic fractures, and practicability and security of both treatments were evaluated.Methods:Retrospective analysis of data of 42 cases of Tile C type pelvic fractures was employed during June 2017 to June 2020. Among them, 32 cases, twenty-four men, eight women, aged 34±6.2 years (range 24-68 years), were treated with percutaneous screw fixation guided by O-arm X wire instrument. According to Tile classification, there were 3 cases of C1.1 type, 8 cases of C1.2 type and 21case of C1.3 type. According to the Denis classification of sacral fractures, 17 cases were in zone I, and 8 cases in zone II. Ten patients, eight males and two females, aged 36±5.2 years (range 19-62 years) were treated by percutaneous screw fixation assisted by orthopedic robot. According to Tile classification, there were 1 case of C1.1 type, 2 cases of C1.2 type and 7 cases of C1.3 type. According to the Denis classification of sacral fractures, there were 5cases in zone I, 2 cases in zone II. For those who got obviously displaced pelvic fractures, Starr frames were used and then internal fixation was used to fix pelvic anterior ring and posterior ring injury respectively. Based on the times of needle adjustments, intraoperative fluoroscopy time, good screw position and incidence of complications two groups were statistically analysed. Matta score was employed to evaluate the quality of fracture reduction, while the Majeed score was employed to evaluate the clinical efficacy. Through the two groups of cases guide needle adjustment times, intraoperative fluoroscopy time, screw position excellent and good rate and the incidence of complications, which were statistically analyzed.Results:All screw positions were confirmed by CT scan after operation. The average time required for each screw placement of the O-arm group was 7.36±2.63 s, of the robot group was 6.80±3.20 s, so difference was not statistically significant ( P<0.05). An average of screw adjustments per one screw was 1.56±0.02 times by O-arm, and by the robot group was 0.34±0.06 times, so differences between the two groups were statistically significant ( P>0.05). The average operating time of O-arm group was 53.86±15.06 min, while the robot group was 52.52±15.14 min, so differences between the two groups were not statistically significant ( P>0.05). Position distribution of screw placement in two groups, all screws in O-arm group of position evaluations were excellent, excellent rate was 100%, all screw position evaluations by robot were excellent, excellent rate was 100%, so difference in screw distribution between the two groups was not statistically significant ( P>0.05). All cases were followed up for 6-12 months. Fracture healing time: 34.6±8.6 weeks for O-arm group, 33.4±9.4 weeks for robot group. Comparison between the two groups was not statistically significant ( P>0.05). Majeed score of O-arm group was 55-87, including Excellence of 17 cases, goodness of 9, fairness of 6. The rate of excellence and goodness was 81.2%, while robot group was 76-95, and that were excellent 7 cases,1 good, and the excellent and good rate was 80%, there was no significant difference between Matta and Majeed score between the two groups ( P>0.05). The incidence of complications between the two groups were no statistically significant ( P>0.05). Conclusion:Orthopedic robot system and O-arm navigation system assisted by percutaneous hollow screw fixation treatment of pelvic anterior and posterior ring injury, which are accurate, safe, minimally invasive, can reduce radiation damage to patients and surgeons. The efficacy were satisfactory. Both treatments are ideal for minimally invasive treatment of pelvic fractures, and the orthopedic robot have advantages of being programmed, standardized, stable and it’s learning curve is shorter.

Objective:To investigate the feasibility and clinical efficacy of percutaneous screw fixation for acetabular anterior column fracture with laser-assisted axial fluoroscopy.Methods:Data of 20 patients (22 sided) with acetabular anterior column fracture treated by percutaneous screw fixation with laser-assisted axial fluoroscopy from January 2017 to December 2018 were retrospectively analyzed. There were 11 males and 9 females with an average of 42.1±3.2 years (range, 24-68 years). There were 7 cases of unilateral acetabular anterior column fracture, 2 cases of bilateral acetabular anterior column fracture (4 sides), 7 cases of anterior column with ipsilateral sacral fracture, and 4 cases of anterior column with sacroiliac joint injury. There were 3 hips of Area I, 6 Area II, 13 Area III of acetabular anterior column fractures according to Nakatani partition. The time from injury to surgery was 5 days (range, 3-11 days). All patients with acetabular anterior column fractures were fixed by percutaneous screw fixation with laser-assisted axial fluoroscopy, and patients with sacral fracture or sacroiliac joint injury were fixed by percutaneous sacroiliac screws with Starr frame-assisted reduction. The time of operation, the number of intraoperative fluoroscopy and the amount of intraoperative bleeding were recorded. Matta scoring criteria were used to assess fracture reduction quality, and hip function was assessed at the last follow-up according to the modified Merle D' Aubigné and Postel scoring system.Results:The average operative time was 22±10 min (range, 20-40 min) with an average times of intraoperative fluoroscopy of 30±8 times (range, 21-45 times), and the amount of intraoperative blood loss was 20±5 ml (range, 10-40 ml). 20 patients were followed up after operation for a period of 14±3.1 months (range, 12-18 months). The quality of postoperative fracture reduction was assessed according to the Matta acetabular fracture reduction criteria: anatomical reduction in 18 hips, satisfactory reduction in 2 hips, unsatisfactory reduction in 2 hips, with an excellent and good rate of 91% (20/22). The fracture healing time was 13±2.2 weeks (range, 11-16 weeks). At the lastest follow-up, hip function was assessed according to the modified Merle D' Aubigné and Postel scoring system: excellent 18, good 3, fair 1, and the satisfactory rate was 95%(21/22). No major neurological, vascular injury, wound infection and ectopic ossification were found during follow-up.Conclusion:Using laser-assisted axial fluoroscopy percutaneous screw to treat acetabular anterior column fracture, the operation is simple. And there is low risk to damage important blood vessels and nerves. This method can shorten the operation time of acetabular anterior column fracture, reduce the amount of blood loss during the operation, and the outcome is satisfactory.