Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Left ventricular hypertrophy(LVH)is one of the common target organ damage of hypertension."Yang leading to qi and yin leading to formation"is the basic form of human material and energy metabolism and disease development.The pathogenesis of hypertension LVH is inseparable from the imbalance of yin and yang.The deficiency of"yang leading to qi"leads to the decline of zang-fu function,deficiency of qi and blood,and the excess of"yin leading to formation"leads to the accumulation of pathological products such as phlegm and fluid,both of which are important pathogenesis of hypertensive LVH.Hypertensive LVH can be seen at the beginning of yin deficiency and yang hyperactivity,liver hyperactivity and wind movement,qi and blood deficiency,and later yin and yang deficiency,phlegm and blood stasis interjunction and other symptoms.In the treatment of hypertensive LVH,the early stage should be based on nourishing yin and extinguishing wind,regulating qi and blood,and the later stage should be based on supplementing yin and yang,expelling phlegm and promoting blood,so as to improve the clinical efficacy of TCM treatment of this disease.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

Left ventricular hypertrophy(LVH)is one of the common target organ damage of hypertension."Yang leading to qi and yin leading to formation"is the basic form of human material and energy metabolism and disease development.The pathogenesis of hypertension LVH is inseparable from the imbalance of yin and yang.The deficiency of"yang leading to qi"leads to the decline of zang-fu function,deficiency of qi and blood,and the excess of"yin leading to formation"leads to the accumulation of pathological products such as phlegm and fluid,both of which are important pathogenesis of hypertensive LVH.Hypertensive LVH can be seen at the beginning of yin deficiency and yang hyperactivity,liver hyperactivity and wind movement,qi and blood deficiency,and later yin and yang deficiency,phlegm and blood stasis interjunction and other symptoms.In the treatment of hypertensive LVH,the early stage should be based on nourishing yin and extinguishing wind,regulating qi and blood,and the later stage should be based on supplementing yin and yang,expelling phlegm and promoting blood,so as to improve the clinical efficacy of TCM treatment of this disease.

Objective To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty(PKP)of vertebrae following local anesthesia.Methods From August 2019 to June 2021,118 patients with thora-co lumbar osteoporotic fractures were treated and divided into observation group and control group,with 59 patients in each gruop.In observation group,there were 26 males and 33 females,aged from 57 to 80 years old with an average of(67.69±4.75)years old;14 patients on T11,12 patients on T12,18 patients on L1,15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group.In control group,there were 24 males and 35 females,aged from 55 to 77 years old with an average of(68.00±4.43)years old;19 patients on T11,11 patients on T12,17patients on L1,12 patients on L2;the same amount of normal saline was injected intramuscularly in control group.Observation indicators included operation time,intraoperative bleeding,visual analogue scale(VAS)evaluation and recording of preoperative(T0),intraoper-ative puncture(T1),and working cannula placement(T2)between two groups of patients,at the time of balloon dilation(T3),when the bone cement was injected into the vertebral body(T4),2 hours after the operation(T5),and the pain degree at the time of discharge(T6);adverse reactions such as dizziness,nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery.Results All patients were successfully completed PKP via bilateral pedicle ap-proach,and no intravenous sedative and analgesic drugs were used during the operation.There was no significant difference in preoperative general data and VAS(T0)between two groups(P＞0.05).There was no significant difference in operation time and intraoperative blood loss between the two groups(P＞0.05).VAS of T1,T2,T3,T4 and T5 in observation group were all lower than those in control group(P＜0.05),and there was no significant difference in T6 VAS(P＞0.05).T6 VAS between two groups were significantly lower than those of T0,and the difference was statistically significant(P＜0.05).There was no signifi-cant difference in incidence of total adverse reactions between two groups(P＞0.05).There was a statistically significant differ-ence in the acceptance of repeat PKP surgery(P＜0.05).Conclusion Half an hour before operation,intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia,which could increase the comfort of patients during operation and 2 hours after operation,and improve patients satisfaction with surgery.

Objective To investigate the clinical effect of minimally invasive transforaminal lumbar interbody fusion(Mis-TLIF)technique combined with preoperative position reduction in the treatment of spondylolisthesis and summarize its advan-tages.Methods Between July 2016 and July 2022,60 patients with lumbar isthmic spondylolisthesis were retrospectively ana-lyzed,including 26 males and 34 females,with an average age of(51.32±4.24)years old ranging from 35 to 72 years old.They were divided into observation group and control group according to the operation methods.There were 30 patients in the obser-vation group,including 12 males and 18 females;the age ranged from 35 to 71 years old with an average of(51.80±6.38)years old,the course of disease ranged from 12 to 60 months with an average of(24.17±1.98)months;there were 18 cases of L4 spondylolisthesis and 12 cases of L5 spondylolisthesis;according to Meyerding classification,there were 20 cases of grade Ⅰspondylolisthesis and 10 cases of grade Ⅱ.The observation group was treated with preoperative postural reduction combined with intraoperative reduction assisted minimally invasive transforaminal lumbar fusion via Quadrant channel(Mis-TLIF).There were 30 patients in the control group,including 14 males and 16 females,with an average of(50.00±4.24)years old ranging from 36 to 72 years old;the course of disease ranged from 12 to 60 months with an average of(23.70±1.53)months;there were 16 cases of L4 spondylolisthesis and 14 cases of L5 spondylolisthesis;according to Meyerding classification,there were 19 cases of grade Ⅰ spondylolisthesis and 11 cases of grade Ⅱ.The control group was treated with open transforaminal lumbar interbody fusion(Open-TLIF).The differences of operation time,intraoperative and postoperative blood loss,hospital stay,radiation exposure time and complications between the two groups were analyzed.Visual analogue scale(VAS),Oswestry disability index(ODI)and Japanese Orthopaedic Association(JOA)score were used to evaluate the clinical effect.X-ray and CT were followed up to evaluate the interbody fusion.Results All patients were followed up for 12 months.There was no signifi-cant difference in operation time,VAS of low back pain,slip angle and slip rate between two groups(P＞0.05).The intraoperative and postoperative blood loss in the observation group(165.50±15.56)ml and(59.17±10.59)ml were less than those in the con-trol group(259.33±35.32)ml and(165.33±29.56)ml(P＜0.05).The length of hospital stay in the observation group(3.53±0.68)days was less than that in the control group(5.20±0.41)days(P＜0.05).The intervertebral space height,slip angle,slip rate,ODI,VAS and JOA scores were significantly improved in the two groups at the final follow-up(P＜0.05).There were signifi-cant differences in ODI[(9.93±1.11)％vs(10.93±1.11)％]and JOA[(26.07±1.01)points vs(25.43±1.25)points]between the observation group and the control group at the final follow-up(P＜0.05).Conclusion In the treatment of spondylolisthesis,preoperative position reduction combined with intraoperative reduction assisted Mis-Tlif technique has advantages of less trau-ma,less bleeding and shorter hospitalization period than traditional open surgery.It is a safe and effective technique.

Objective:To investigate the effects of Ziyin Liangxue formula combined with prednisone on immune function and the ST2/IL-33 pathway in mice with immune thrombocytopenia.Methods:In 40 BALB/c mice,32 were constructed as immune thrombocytopenia mouse models by antiplatelet serum injection.After successful modeling,the mice were randomly divided into model group,Ziyin Liangxue formula group(0.2 ml/10 g),prednisone group(0.2 ml/10 g),and Ziyin Liangxue formula+prednisone group(0.2 ml/10 g),8 mice in each group,and the other 8 mice were set as control group.The drugs were administered by gavage at the dose,and the model group and control group were given equal amounts of saline by gavage once a day for 2 weeks of continuous intervention.Blood samples and spleen tissues were collected,the peripheral platelet count was measured by automatic hematology analyzer,the pathological changes in spleen tissue was observed by HE staining,the levels of serum transforming growth factor(TGF)-β,interleukin(IL)-17,and peripheral blood thrombopoietin(TPO)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of IL-33,sST2,and ST2 in spleen tissue was detected by Western blot,and the cell counts of peripheral blood Th17 and Treg were detected by flow cytometry.Results:Compared with the control group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly decreased(P＜().05),while the level of IL-17,Thl7 cells,and the expression of IL-33,sST2,and ST2 protein were significantly increased in the model group(P＜0.01).Compared with the model group,the number of platelets,the level of TPO,TGF-β,and Treg cells were significantly increased(P＜0.05),while the level of IL-17,Th17 cells,and the expression of IL-33,sST2,and ST2 protein were significantly decreased in the Ziyin Liangxue formula+prednisone group(P＜0.01).Conclusion:Ziyin Liangxue formula+prednisone can effectively regulate Th17/Treg balance,thus effectively improve immune thrombocytopenia,and the mechanism may be related to the regulation of ST2/IL-33 signaling pathway.