Background Polycyclic aromatic hydrocarbons represented by benzo[a]pyrene are among the most significant occupational and environmental pollutants. Exposure to benzo[a]pyrene during pregnancy can cause delayed intellectual development in offspring, and the mechanism may be related to the expression of protocadherin (Pcdh), a key molecule for learning and memory. Objective To explore the possible role of Pcdh in impaired learning and memory function of pups caused by benzo[a]pyrene exposure during pregnancy by establishing an animal model of cognitive impairment in pups caused by benzo[a]pyrene exposure during pregnancy, and detecting the expression of Pcdh and its transcription-related factors in the hippocampal tissues of pups at different developmental stages. Methods Sixty female and male SPF-grade rats were caged in a 1:1 ratio overnight, and the successfully mated female mice were randomly divided into blank control, 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups, with 6 mice in each group. They were intraperitoneally injected with benzo[a]pyrene from the 17th to the 19th day of pregnancy to establish an exposure model. Learning and memory functions of the offspring were tested through Morris water maze on the 45th day after the birth (PND) of the pups. On the PND45 and PND75 of the pups, hippocampal tissues of 6 pups (per group) were collected respectively. The expression levels of PcdhαC1 and wings apart-like homolog (WAPL) genes and proteins were detected by fluorescence quantitative polymerase chain reaction (PCR) and Western blotting. Results The results of Morris water maze showed that there was no interaction between the escape latency time of the pups and the dose groups of 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ (F _{time × group}=0.515, P>0.05). The escape latency of pups decreased with increase of training time (F _time=24.678, P<0.001, F _group=12.803, P<0.001). The PCR results showed that at PND45, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). At PND75, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 20 mg·kg⁻¹ and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). The Western blotting results showed that at PND45, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). At PND75, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). Conclusion Exposure to benzo[a]pyrene during pregnancy can cause impairment in the learning and memory abilities of PND45 offspring and may alter the expression of PcdhαC1 and WAPL genes and proteins.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.

Objective To analyze ancient prescriptions for knee osteoarthritis(KOA),and explore their application patterns,for providing clinical reference value.Methods Prescriptions were collected from ancient documents,and a database was created by using Excel 2016 for frequency analysis.Association rules and hidden structures were analyzed by using SPSS Modeler 18.0 and Lantern 5.0.Results A total of 373 prescriptions and 421 herbs were collected,with 3894 times of frequency of medication.Danggui was the most frequently used herb.Herbs primarily tonified deficiencies,relieved exterior symptoms,and expelled wind-dampness,with warm properties and pungent,sweet,or bitter tastes,mainly targeting the spleen and kidney meridians.Thirteen strong association rules were identified,including Chuanxiong+Niuxi-Danggui,and Bixie-Niuxi.Hidden structure analysis revealed 10 variables,leading to 4 clusters and 4 core prescriptions.Common syndromes included wind-damp,wind-cold-damp,wind-damp-heat,and qi-blood deficiency.Conclusion The treatment of KOA in ancient literature focuses on dispelling wind and removing dampness,taking into account both positive deficiency and evil excess,flexible use of tonifying spleen and kidney,clearing dampness-heat,tonifying Qi and blood and other drugs.

Objective To analyze ancient prescriptions for knee osteoarthritis(KOA),and explore their application patterns,for providing clinical reference value.Methods Prescriptions were collected from ancient documents,and a database was created by using Excel 2016 for frequency analysis.Association rules and hidden structures were analyzed by using SPSS Modeler 18.0 and Lantern 5.0.Results A total of 373 prescriptions and 421 herbs were collected,with 3894 times of frequency of medication.Danggui was the most frequently used herb.Herbs primarily tonified deficiencies,relieved exterior symptoms,and expelled wind-dampness,with warm properties and pungent,sweet,or bitter tastes,mainly targeting the spleen and kidney meridians.Thirteen strong association rules were identified,including Chuanxiong+Niuxi-Danggui,and Bixie-Niuxi.Hidden structure analysis revealed 10 variables,leading to 4 clusters and 4 core prescriptions.Common syndromes included wind-damp,wind-cold-damp,wind-damp-heat,and qi-blood deficiency.Conclusion The treatment of KOA in ancient literature focuses on dispelling wind and removing dampness,taking into account both positive deficiency and evil excess,flexible use of tonifying spleen and kidney,clearing dampness-heat,tonifying Qi and blood and other drugs.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.

It is necessary to develop rapid and living guidelines in order to improve the evidence translation and guidance for clinical practice in emergency situations， and to enhance the participation of traditional Chinese medicine （TCM） in management of emergencies. This paper introduced the process of developing rapid and living guidelines of TCM and divided it into three stages， that is preparation， rapid development and dynamic updating， which highlights the features of rapid development， high quality， and dynamic updating and the integration with the predominance of TCM. By comparing with general guidelines on composition， personnel number， timing to formulate and communication patterns of the guideline working groups， as well as the content and number of clinical questions， this paper mainly gave suggestions on how to formulate a concise but authoritative team during the preparation stage， how to efficiently manage the guideline team and promote the development process from conflict of interest management， working and communication mode adjustment， and how to formulate and update the important and prioritized clinical questions， all of which may provide reference for the development of TCM rapid and living guidelines.

The lack of direct evidence is an important problem faced in the formation of recommendations in rapid living guidelines of traditional Chinese medicine under public health emergencies， and the supplementation of indirect evidence can be a key method to solve this problem. For the collection of evidence， the type of evidence required， including direct and indirect evidence， should be clarified， and ‘direct first’ principle for selecting evidence can be set to standardize and accelerate the guideline development. When integrating evidence， recommendations can be formed directly if there is sufficient direct evidence， while regarding insufficient direct evidence， recommendations need to be supplemented and improved by integrating indirect evidence. In addition， when the body of evidence contains evidence from multiple sources， it is suggested to rate the evidence according to “higher rather than lower” principle. Finally， when forming recommendations， the level of evidence， safety and economic efficiency should be taken into consideration to determine the strength of the recommendation.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

Objective:To investigate the relationship of the acute radiation reactions of totalbody irradiation before hematopoietic stem cell transplantation with the different total and fractionated doses of irradiation.Methods:The clinical data of 48 patients who underwent 6 MV X-ray total body irradiation pretreatment from May 2015 to December 2019 in Shijiazhuang Ping'an Hospital before undergoing hematopoietic stem cell transplantation were retrospectively analyzed. The patients were divided into 8 Gy group (12 cases), 10 Gy group (31 cases) and 12 Gy group (5 cases) according to the total radiation dose, and divided into 4 Gy/f group (17 cases) and 5 Gy/f group (31 cases) according to the fractionated radiation dose. Acute radiation reactions in the oral mucosa, pharynx, salivary glands, upper gastrointestinal tract, lower gastrointestinal tract and lung of patients in each group after radiotherapy were summarized and compared.Results:Acute pharyngeal reaction in the total radiation dose of 8 Gy group showed that 11 cases (91.7%) were grade 0 and 1 case (8.3%) was grade 1; in the total radiation dose of 10 Gy group, 10 cases (32.3%) were grade 0, 13 cases (41.9%) were grade 1, 4 cases (12.9%) were grade 2, 3 cases (9.7%) were grade 3, and 1 case (3.2%) was grade 4; in the total radiation dose of 12 Gy group, 2 cases (40.0%) were grade 0, 1 case (20.0%) was grade 1, 1 case (20.0%) was grade 2, and 1 case (20.0%) was grade 3. The severity of acute pharyngeal radiation reaction in the total radiation dose of 8 Gy group was better than that in the 10 Gy and 12 Gy groups, and the difference was statistically significant ( χ2 = 11.338, P = 0.003); there was no significant difference in the incidence of acute radiation reactions in other parts (all P > 0.05). Acute pharyngeal radiation reaction in the fractionated radiation dose of 4 Gy/f group showed that 13 cases (76.5%) were grade 0, 2 case (11.8%) was grade 1, 1 case (5.9%) was grade 2, and 1 case (5.9%) was grade 3; in the 5 Gy/f group, 10 cases (32.3%) were grade 0, 13 cases (41.9%) were grade 1, 4 cases (12.9%) were grade 2, 3 cases (9.7%) were grade 3, and 1 case (3.2%) was grade 4. The severity of acute pharyngeal radiation reaction in the fractionated radiation dose 4 Gy/f group was better than that in the 5 Gy/f group, and the difference was statistically significant ( Z = -2.606, P = 0.009); there was no significant difference in the incidence of acute radiation reactions in other parts (all P > 0.05). Conclusion:The total dose of 8 Gy and fractionated dose of 4 Gy/f in the total body irradiation before hematopoietic stem cell transplantation can alleviate the acute pharyngeal radiation reaction.

Objective:To investigate the safety and clinical efficacy of laparoscopy dominated approaches to two different local resections for duodenal stromal tumors.Methods:From May 2015 to May 2021 25 duodenal stromal tumors cases were allocated to wedged resection group (8 cases) and segmental resection (17cases).Results:Compared with the segmental resection group, the operative time in the wedge resection group was significantly shorter [(202±43) min vs. (299±128) min, t=-2.814, P=0.010]. The intraoperative blood loss was 20 (10-50) ml in the wedge resection group and 30 (15-100) ml in the segmental resection group ( t=-1.128, P>0.05). Patients in the wedge resection group had a significantly shorter postoperative hospital stay, 7(9-11) days vs. 14 (10-28) days, t=-2.66, P=0.008. There was no difference in the incidence of postoperative complications and gastric emptying disorders between the two groups ( P>0.05). Conclusion:In spite of laparoscopic,robotic or open approaches, wedge resection and segmental resection based on anatomic location for duodenal stromal tumors are both safe and satisfactory.