Shugan Jianpi Yangxin Prescription Regulates Orexin-A and Its Receptors in Mouse Model of Insomnia / 中国实验方剂学杂志

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Pulmonary Nodules / 中国实验方剂学杂志

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism.@*METHODS@#MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot.@*RESULTS@#RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.@*CONCLUSION@#RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway / 亚洲男科学杂志(英文版)

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Study on the effects and mechanism of total glucosides of paeony on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside in the treatment of eczema / 中国药房

OBJECTIVE To investigate the effects of total glucosides of paeony （TGP） on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside （TWP） in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2，4-dinitrofluorobenzene-acetone olive oil solution （volume ratio was 4∶1） on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group， loratadine group （0.9 mg/kg）， TWP group （9.45 mg/kg）， TGP group （162 mg/kg） and compatibility group （TWP 9.45 mg/kg+TGP 162 mg/kg）， with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization， administration groups were given relevant medicine intragastrically， and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically， once a day， for consecutive 21 d. Twenty-four hours later after the final administration， the general condition of rats in each group was observed， and the eczema area and severity index （EASI） were scored； ear swelling degree of rats was measured， and the skinhistomorphology observation and pathological score were performed； protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase （p38 MAPK）， phosphorylated p38 MAPK （p- MAPK） and phosphorylation level of p38 MAPK in rat skin tissue were detected； the levels of inflammatory indexes （interleukin-4， interferon- γ）， liver and kidney function indexes [glutamic-pyruvic transaminase （GPT）， glutamic-oxaloacetic transaminase （GOT）， serum creatinine （SCr） and blood urea nitrogen （BUN）] and oxidant stress indexes [total superoxide dismutase （T-SOD） and malondialdehyde （MDA）] were measured. RESULTS Compared with normal group， EASI score， ear swelling degree， pathological score， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation level of p38 MAPK， the levels of inflammatory indexes and BUN were all increased significantly in model group （P＜0.05）. Compared with model group， EASI scores， ear swelling degree， pathological scores， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups （P＜0.05）. The levels of GPT， GOT， SCr and BUN were increased significantly in TWP group， while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly （P＜0.05）. The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group， while the levels of MDA were increased significantly （P＜0.05）. The compatibility group showed more obvious effect in improving the ear swelling degree， pathological score， p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes， and could reverse the abnormality of liver and kidney indexes caused by TWP （P＜0.05）. CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory， synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.

Development and characteristics of automatic ash-removal heat-sensitive moxibustion device / 中国针灸

An automatic ash-removal heat-sensitive moxibustion device was developed, which could keep relatively constant temperature of heat-sensitive moxibustion, and realize the automatic ignition and automatic ash removal of moxa sticks during heat-sensitive moxibustion. The automatic ash-removal heat-sensitive moxibustion device comprises a bracket and a moxibustion box fixed on the top of the bracket; the bracket is composed of a base and a movable telescopic arm. This device can solve the problems of temperature instability, moxa ash blocking heat transfer and moxa ash falling during heat-sensitive moxibustion, avoiding the scalding caused by moxa ash falling, and reduce the workload of medical staff.

Assessing the impact of educational methods on influenza vaccine uptake and patient knowledge and attitudes: a randomised controlled trial

INTRODUCTION@#Although influenza vaccination reduces rates of pneumonia, hospitalisation and mortality, influenza vaccination uptake remains low in older patients. The primary aim was to compare individualised counselling with educational pamphlets alone in improving influenza vaccination uptake. The secondary aims were to evaluate knowledge and attitudes towards influenza vaccination and factors influencing uptake.@*METHODS@#A randomised controlled study was conducted in two government polyclinics with 160 participants per arm. Patients aged 65 years and above attending for doctor consultation were recruited. All participants received an educational pamphlet on influenza vaccination. The intervention group received additional face-to-face counselling. Participants filled a pre- and postintervention questionnaire assessing knowledge of influenza and attitudes towards the vaccine. Follow-up calls and verification of electronic records was done at three months to determine actual vaccine uptake.@*RESULTS@#At three months, 16 (10%) patients in the intervention group and 20 (12.5%) patients in the control group had completed influenza vaccination (P = 0.48). Factors positively associated with vaccine uptake were willingness to receive vaccination immediately after intervention (adjusted odds ratio [OR] 12.15, 95% confidence interval [CI] 4.42-33.38), and male gender (adjusted OR 2.96, 95% CI 1.23-7.12). Individualised counselling was more effective in improving knowledge (P < 0.01). Overall knowledge scores did not influence actual vaccine uptake rates. (adjusted OR 1.10 [0.90-1.3]).@*CONCLUSION@#Both arms of patient education increased uptake of influenza vaccination. Individualised counselling was not superior to pamphlets alone in improving uptake. Performing vaccination at the initial point of contact improves actual uptake rates.

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity / 中华胃肠外科杂志

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China / 中华流行病学杂志

Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.

Persistence follow-up of immune memory to hepatitis B vaccine among infants with non- and low-response to primary vaccination after revaccination with three doses / 中华预防医学杂志

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVES@#Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups.@*RESULTS@#The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T1/2), area under the curve (AUC), time to reach maximum concentration (Tmax). Compared with the control group, AUC was increased by 23.5%, Tmax and T1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population.@*CONCLUSIONS@#Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.

Neoadjuvant PD-1 Inhibitor Plus Apatinib and Chemotherapy Versus Apatinib Plus Chemotherapy in Treating Patients With Locally Advanced Gastric Cancer: A Prospective, Cohort Study

Purpose@#This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). @*Materials and Methods@#Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. @*Results@#The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. @*Conclusions@#Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

Current research status of traditional Chinese medicine in the prevention and treatment of hepatocellular carcinoma by regulating the JAK/STAT signaling pathway / 临床肝胆病杂志

Hepatocellular carcinoma （HCC） is one of the common malignant tumors of the digestive tract and seriously threatens the life of patients due to a high incidence rate， a high degree of malignancy， strong invasion and metastasis， and poor prognosis. At present， the main methods for the prevention and treatment of HCC include drugs， surgery， and interventional treatment， but all of these methods have certain adverse reactions and side effects. As an important intracellular signal transduction pathway in the human body， the JAK/STAT signaling pathway mainly exerts an anti-HCC effect by regulating cell invasion， metastasis， proliferation， growth， apoptosis， autophagy， angiogenesis， inflammation/immune response， iron metabolism， and drug resistance. Therefore， targeting the JAK/STAT signaling pathway plays an important role in the prevention and treatment of the development and progression of HCC. Traditional Chinese medicine has attracted wide attention due to its advantages of multiple targets， pathways， components， and levels in the treatment of HCC， and many cell or animal experiments on traditional Chinese medicine in the treatment of HCC have shown that the JAK/STAT signaling pathway is an important target for the prevention and treatment of HCC， with the effects of improving liver function， reducing HCC recurrence， and improving immunity. Based on this， this article analyzes the mechanism of action of the JAK/STAT signaling pathway in HCC， as well as the intervention effect of traditional Chinese medicine monomers， traditional Chinese medicine extracts， and traditional Chinese medicine compounds on the JAK/STAT signaling pathway， in order to provide theoretical basis and reference for the prevention and treatment of HCC and the research and development of new traditional Chinese medicine drugs.

ABO-incompatible living-related kidney transplantation: report of 23 cases / 器官移植

Objective To evaluate clinical efficacy and safety of ABO-incompatible (ABOi) living-related kidney transplantation. Methods Clinical data of 23 recipients undergoing ABOi living-related kidney transplantation were retrospectively analyzed. According to the initial blood group antibody titers in the recipients before surgery, different individualized pretreatment regimens were adopted, including oral intake of immunosuppressive drugs plus rituximab, or oral intake of immunosuppressive drugs plus plasma exchange and/or double filtration plasmapheresis plus rituximab. The blood group antibody titers before and after pretreatment, before and after kidney transplantation, and perioperative renal function and related complications were monitored. Renal allograft function and related complications were observed during postoperative follow-up. Results Among 23 recipients undergoing ABOi living-related kidney transplantation, except for one case presenting with hyperacute rejection during operation, the serum creatinine levels of the remaining 22 recipients were restored normal. Perioperative complications included lymphatic fistula in 4 cases, 1 case of urinary fistula, 1 case of perirenal hematoma complicated with T cell-mediated rejection, 6 cases of urinary system infection, 1 case of acute tubular necrosis, 1 case of acute pancreatitis, 1 case of blood group antibody titer rebound, and 1 case of primary disease recurrence, and all of these complications were cured after corresponding treatment. During postoperative follow-up, the graft and recipient survival rates of 22 recipients were 100%, and renal allograft function was normal. The blood group antibody titer were all ≤1:8 during follow-up. Complications during follow-up included 2 cases of severe lung infection, 1 case of antibody-mediated rejection, 2 cases of primary disease recurrence, 1 case of lymphocyst, 1 case of urinary system infection, 1 case of herpes zoster, 1 case of BK viruria and 2 cases of abnormal blood glucose levels. Conclusions ABOi living-related kidney transplantation may be safely performed by selecting individualized pretreatment regimens according to antibody titers by different blood groups. However, high-dose rituximab or combined use of rabbit anti-human thymocyte immunoglobulin may cause severe infectious complications in highly sensitized recipients.

Neoadjuvant immunotherapy combined with stereotactic body radiation therapy for stage Ⅲ/N2 non-small cell lung cancer: Three cases reports / 中国胸心血管外科临床杂志

@#We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.

Effect and Mechanism of Baoshen Prescription in Alleviating Renal Fibrosis in UUO Mice by Regulating ERK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the protective effect of Baoshen prescription against renal fibrosis and explore its underlying mechanism through network pharmacology， molecular docking， and in vivo experiments. MethodAll mice were randomly divided into sham surgery group， model group， low-， medium-， and high-dose Baoshen prescription groups， and a benazepril hydrochloride group. Unilateral ureteral obstruction （UUO） was performed to establish a renal fibrosis model， and the administration of Baoshen prescription at low， medium， and high doses （0.455， 0.91， and 1.82 g·kg-1）， and benazepril hydrochloride （1.68 mg·kg-1） or distilled water began on the same day as model preparation. Mice in the model group and the sham surgery group were given an equal volume of distilled water. The intervention was carried out once daily for 14 days. Mouse serum levels of blood urea nitrogen （BUN） and creatinine （Cr） were measured. Hematoxylin-eosin （HE） staining and Masson staining were used to observe renal pathological changes. Western blot and immunohistochemistry were used to assess the expression of fibronectin （FN）， α-smooth muscle actin （α-SMA）， and E-cadherin， which are related to renal fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， NOD-like receptor protein 3 （NLRP3）， and monocyte chemoattractant protein-1 （MCP-1） in renal tissues. The mechanism of Baoshen prescription in improving renal fibrosis was explored through network pharmacology， molecular docking， and Western blot experiments. ResultCompared with the sham surgery group， the model group showed significantly increased levels of BUN and Cr （P<0.01）. The model group exhibited abnormal renal glomerular morphology， loss of tubular brush borders， tubular dilation， and an enlarged area of blue collagen fibers. Mice in the model group showed significantly elevated levels of FN and α-SMA （P<0.01）， significantly decreased expression of E-cadherin （P<0.01）， and significantly increased expression of TGF-β1， TNF-α， NLRP3， and MCP-1 mRNA （P<0.05， P<0.01）. Compared with the model group， the Baoshen prescription groups showed significantly reduced BUN and Cr levels （P<0.01）， alleviated renal pathological damage， improved fibrosis， reduced expression of FN and α-SMA （P<0.01）， increased E-cadherin expression （P<0.01）， and downregulated mRNA expression of TGF-β1， TNF-α， NLRP3， and MCP-1 （P<0.05， P<0.01）. Network pharmacology and molecular docking predicted that Baoshen prescription could potentially improve renal fibrosis through the extracellular signal-regulated kinase （ERK）/p38 mitogen-activated protein kinase （MAPK） signaling pathway. Pharmacological research showed that compared with the sham surgery group， the model group exhibited significantly increased expression of phosphorylated （p）-ERK and p-p38 （P<0.05， P<0.01）. Compared with the model group， medium- and high-dose Baoshen prescription groups showed significantly downregulated expression of p-ERK and p-p38 proteins （P<0.05， P<0.01）. ConclusionBaoshen prescription can effectively improve renal fibrosis induced by UUO in mice， and its mechanism of action may be related to the ERK/p38 MAPK signaling pathway.

Spontaneous intracranial hypotension: analysis of 118 patients ' clinical characteristics / 中华神经科杂志

Objective:To summarize the clinical features, radiological characteristics, therapy, and outcome of patients with spontaneous intracranial hypotension (SIH).Methods:The general information, clinical manifestations, auxiliary examinations, treatment, and outcomes in consecutive patients of SIH hospitalized in the Xuanwu Hospital, Capital Medical University from November 2018 to October 2022 were analyzed.Results:A total of 118 patients with a female-to-male ratio of 5∶4 were included and the ages were 17.00-71.00[39.00(34.00,46.75)]years with a preponderance in the age of 30-49 years. Almost all patients had orthostatic headaches (117/118, 99.2%), accompanied by nausea (90/118, 76.3%), vomiting (70/118, 59.3%), neck stiffness (88/118, 74.6%), tinnitus (57/118, 48.3%), and ear fullness (57/118, 48.3%). Brain magnetic resonance imaging (MRI) showed dural enhancement (97/113, 85.8%), enlarged venous sinus (88/113, 77.9%), subdural fluid collection (46/113, 40.7%), decreased suprasellar cistern (86/113, 76.1%), effacement of the prepontine cistern (86/113, 76.1%), diminished mamillopontine distance (80/113, 70.8%). The cerebrospinal fluid (CSF) leaks were detected in 90.7% (107/118) of the patients by magnetic resonance myelography but 54.3% (25/46) and 52.6% (20/38) by CT myelography and magnetic resonance myelography with gadolinium. Lumber puncture found CSF pressure<60 mmH 2O (1 mmH 2O=0.009 8 kPa) in 18.4% (19/103) of patients, increased CSF red blood cell counts in 50.6% (44/87) of patients, CSF pleocytosis in 44.8% (39/87) of patients, increased CSF protein concentrations in 57.5% (50/87) of patients. The headache completely disappeared after conservative treatment in 24.6% (31/118) of patients and after a single targeted epidural blood patch in 89.7% (78/87) of patients. A rebound headache after epidural blood patch treatment occurred in 66.0% (58/87) of patients. Conclusions:The patients with SIH almost manifested with orthostatic headache, and brain MRI and magnetic resonance myelography were suggested in those patients instead of CSF pressure by lumber puncture. Targeted epidural blood patch was effective and safe in SIH patients.