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Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P <0.001; median PFS: 16.0 months vs 3.0 months, P <0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P =0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P =0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P <0.001; median PFS: 20.0 months vs 2.0 months, P <0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR =3.204, 95% CI 1.068-9.610, P =0.038) for patients with pPCL, while receiving maintenance therapy ( HR =0.075, 95% CI 0.022-0.253, P <0.001) and post-treatment response of VGPR or better ( HR =0.175, 95% CI 0.048-0.638, P =0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P <0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P <0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) ( P <0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P <0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P =0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P =0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg ( P <0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d ( P =0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d ( P =0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P <0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR =2.37, 95% CI 1.30-4.30; HR =4.50, 95% CI 2.35-9.01) and OS ( HR =4.20, 95% CI 1.50-11.80; HR =9.53, 95% CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months ( P <0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively ( P =0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached ( P= 0.324 and P= 0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months ( P =0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months ( P =0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

Objective: To explore the effect of the combined effect of noise and heat on occupational hearing loss of workers by using Meta-analysis method. Methods: In August 2020, the Chinese and English literature on the relationship between exposure to noise and heat and occupational hearing loss published from January 2005 to August 2020 by CNKI, China Biomedical Literature Service System, Wanfang Data Knowledge Service Platform, VIP Official Database, Medline and PubMed Databases were searched, using noise, heat or hyperthermia, hearing as keywords. The selected data were analyzed by Stata 12.0 software, and the combined OR (95% CI ) value included in the literature was calculated. Sensitivity analysis was used to explore the source of heterogeneity and analyze publication bias. Results: A total of 14 literatures (14 in Chinese, 0 in English) were included in the analysis, and 38654 subjects were included, including 6411 workers in the noise and heat combined effect group and 32243 workers in the noise alone group. The probability of hearing loss in the noise and heat combined effect group was 1.39 times higher than that in the noise alone group (95% CI : 1.14-1.69). The effect size OR was stable after sensitivity analysis, and there was no publication bias in the included literatures tested by Egger's and Begg's Method ( z =0.38, P =0.702, t =-0.74, P =0.476) . Conclusion: Simultaneous exposure to noise and heat may increase the risk of hearing loss for workers in noisy workplaces.

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P= 0.024) and PFS (28.7 vs. 24.1 months, P= 0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR =0.644, 95 %CI 0.438-0.947, P= 0.025) and a favorable prognostic factor for PFS ( HR =0.646, 95 %CI 0.457-0.913, P= 0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR =0.705, 95 %CI 0.497-0.998, P= 0.049), but OS was not affected ( P> 0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P= 0.047), but not OS (63.4 vs.43.1 months, P= 0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P <0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Objective: To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1∶1 scale, 64 in each group, and correlation analysis was performed. Results: A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients ( P =0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P =0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P =0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS ( HR =0.448, 95% CI 0.260-0.771, P =0.004) and PFS ( HR =0.446, 95% CI 0.280-0.778, P =0.003) . Conclusion: These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.

Objective: To explore the influence of lateral patellofemoral joint degeneration on the treatment of anteromedial osteoarthritis of knee joint by Oxford medial unicompartmental knee arthroplasty. Methods: The clinical data of 73 patients (73 knees) with knee osteoarthritis underwent unicompartmental knee arthroplasty at Department of Orthopaedic Surgery, Xuanwu Hospital, Capital Medical University from March 2016 to December 2017 were analysed respectively.There were 18 males and 55 females, aged (68.6±7.5) years(range: 53 to 89 years).The lateral patellofemoral joints of patients were evaluated by Ahlback grading system. Patients with Ahlback 0 andⅠ were in the non degenerative group (37 cases), and those with Ahlback Ⅱ and above were in the degenerative group (36 cases). Hospital for special surgery knee score(HSS) and the Western Ontario and McMaster Universities(WOMAC) osteoarthritis index, as well as the condition of kneeling, sit to stand movement, up stair and down stair were recorded. The data before and after operation were compared by paired sample t test, and the data between groups were compared by independent sample t test. χ(2) test was used for counting data. Pearson correlation analysis was used to compare the correlation between ahlback score, HSS and WOMAC osteoarthritis index. Results: The follow-up time was (35.1±6.6) months (range: 25 to 47 months).The knee function of the patients improved significantly after operation.The HSS score increased from 57.7±11.8 preoperative to 81.8±7.8 postoperative ( t= 16.64, P= 0.00) and WOMAC osteoarthritis index decreased from 48.9±13.4 preoperative to 15.6±8.8 postoperative ( t= 20.48, P= 0.00). There was no statistical difference in the change of HSS between the degenerative group and the non-degenerative group before and after surgery(27.5±12.2 vs . 22.5±12.3, t=- 1.65, P= 0.10) as well as the change of WOMAC osteoarthritis index(31.8±14.0 vs . 36.4±13.7, t=- 1.35, P= 0.18), but the lateral patellofemoral joint degeneration was related to inability to complete squats (χ(2)=5.17, P= 0.04) and sitting up (χ(2)=7.22, P= 0.01). Conclusion: The degeneration of lateral patellofemoral joint has no effect on the early functional recovery of patients with anteromedial knee osteoarthritis after Oxford medial unicompartmental knee arthroplasty.

Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) Ⅰ-Ⅱ, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.

Objective: To investigate the effects of berberine in combination with bortezomib on proliferation and apoptosis of multiple myeloma (MM) cell line. Methods: MM cell line U266 cells were treated with berberine and/or bortezomib. The effects of berberine and/or bortezomib on proliferation of cells were measured by methylthiazolyl tetrazolium bromide (MTT). Flow cytometric Annexin Ⅴ/PI double staining method was used to detect effect of either drug alone or in combination on apoptosis of MM cell line U266. ELISA was used to measure the expression of casepase-3,-8,-9 affected by the two drugs. Western blot was used to detect the expression of the apoptosis-related protein TRADD and FADD. King formula was used to determine if there was a synergistic effect of berberine in combination with bortezomib. Results: ① Both berberine and bortezomib as single agent had dose- and time-dependent effects of proliferation inhibition on U266 cells. Berberine (20 μmol/L) and bortezomib (5 nmol/L) had a synergistic effect of proliferation inhibition (Q value: 1.31-1.65). ② The proportion of early stage apoptosis in both single agent groups and combination group significantly increased compared to control group ( P < 0.05). Berberine and bortezomib had a synergistic effect on cell apoptosis (Q value after 6 h and 12 h were 0.896 and 1.197, respectively). ③ Berberine in combination with bortezomib significantly upregulated expressions of caspase-3, -8 and -9, which were statistically significant ( P <0.05). ④Berberine in combination with bortezomib significantly upregulated expressions of TRADD (0.91±0.01, 0.70±0.01) and FADD (0.98±0.01, 0.98±0.01) compared with control group (both P <0.05). Conclusion: Berberine in combination with bortezomib had synergistic effects on proliferation inhibition and apoptosis, which were mediated by up-regulated levels of TRADD and FADD.

The zot gene encoding Zonula occludens toxin was amplified from classic Vibrio cholerae genomic DNA by PCR. The result of sequencing indicated that zot gene encodes 399 amino acid residues. The sequence of zot gene was a little bit different from that of reported including 14 nucleotides and four amino acid residues. The expression plasmid pET-ZOT was constructed by inserting zot gene into plasmid pET-28a(+) containing the T7 promoter. The expression plasmid was induced into E. coli BL21 (DE3) and expression strain BLZOT was selected. SDS-PAGE analysis revealed that the ZOT protein was expressed and accumulated up to above 15% of bacterial soluble protein after induced by IPTG. A protein of 47 kD was expressed as including body. Western blot analysis revealed that the expressed protein was ZOT.

The gene encoding human manganese-superoxide dismutase (Mn-SOD) was fused to anti-carcinoembryonic antigen single-chain antibody gene to construct the fusion gene, then was ligated into prokaryotic expression vector pET-22b(+), The fusion gene was expressed in E. coli at high level, accounting for 24% of the total bacteria soluble protein; and was characterized by SDS-PAGE and Western-blot analysis; the expression product had the CEA-binding ability in RIA, and also had the SOD activity by pyrogallol autoxidation assay. So, the Mn-SOD moiety retains substantial enzymatic activity, where the ScFv moiety can deliver the fusion protein to tumor, Mn-SOD is a potential tumor-suppressor gene, maybe the fusion protein can provide a new pathway to tumor therapy.

The Vk gene of MAb with specificity for HBsAg and human Ck gene have been combined to form chimeric light chain (Vk-Ck) by recombinant PCR, which has combined with VH to construct chimeric single-chain antibody(ScFv-Ck) by a linker encoding a flexible peptide[(Gly3 Ser)3]. The ScFv-Ck has been expressed in the heat-induced expression system and secreted expression system of E. coli respectively. Analysis by Western-blot and indirect ELISA shows that the ScFv-Ck product in two systems both have HBsAg-binding ability, and ScFv-Ck has been secreted from E. coli in the direction of secretion peptide.

Retinoic acid and its analogues play important roles in modulating cell growth, differentiation, immunity and apoptosis. Clinically they are used for cancer chemoprevention and chemotherapy. Based upon the moiety of 3,5-di-t-butyl-4-hydroxy phenyl ring, a series of substituted aromatic amide, ester and chalcones were designed and synthesized, which mimic the molecular shape, size, and spacial disposition of functional groups of retinoic acid. The general structure is as follows: [formula: see text] where R stands for hydrogen atom or methyl group, Y is the linkage -CONH-, -NHCO-, -COO-, -COCH = CH-, or a member of a heterocycle, X represents various substituents at different positions. The SAR indicates that the presence of hydrophobic group(s) at one end of the molecule, and a carboxyl group at the other end, and a conjugative system of molecule are necessary and full prerequisite for exhibiting activity. Loss of any one factor of them will abolish the activity. Being obligatory for anti-oxidative effect, the phenolic hydroxy group does not convey biological activity, because after methylation of the hydroxy group the compound increases the differentiation-inducing activity and loses the anti-oxidative effect, indicating that there is no correlation between the two activities. With a stable conformation of two phenyl rings with cis-conformation N-methylated acyl amide (No. 30) features in bent shape of the molecule, instead of an extended conformer, which is taken by the non-N-methylated partner and all-trans retinoic acid. A bent conformer of No. 30 accounts for the inactivity. In this paper compounds No. 4f, 4g, 5a, 7, 13, 32, 37, and 38 exhibited significant activity among them 4-[3-(3, 5-di-t-4-methoxyphenyl)-3-oxo-1-propenyl] benzoic acid (No. 38) showed high activity comparable to that of retinoic acid. The pharmacological action of No. 38 is under investigation.

Precise prediction of the binding constant of ligand to receptor is an important aspect of structure-based drug design. Almost all methods including de novo design and 3D database search are over concentrated on structure generation rather than quantitative evaluation of the binding properties of the newly produced molecule. Using epididymal retinoic acid binding protein (ERABP) as a model, we simulated the interaction between retinoids and their receptor with DOCK program and obtained an equation for predicting the binding constants. According to the docking conformers of the ligands, CoMFA was also used to deduce a pharmacophoric model of this series of compound.

Effect of panaxatriol ginsenoside (PG) on interleukin-1 (IL-1) gene expression was studied by using wheat germ extract (cell-free translation system) and IL-1 bioassay. The results showed that IL-1 production increased by 40% (487-682 U.ml-1) at maximum during cell culture (0-84 h) after PG (10 micrograms.ml-1) was added to phytohemagglutinin (PHA, 50 micrograms.ml-1) stimulated lymph node cells. Meanwhile, IL-1 mRNA from PHA combined with PG stimulated lymph node cells translated 39.5% more IL-1 than that of PHA-stimulated cells at maximum (2500-3489 U/mg RNA).

Analysis of the quantitative relationship between a series of substituted benzylidenemalononitriles and the inhibitory action on protein tyrosine kinases were carried out using the Hansch-Fujita method. The results indicate that the presence of two or three hydroxy groups attached to a phenyl ring, which connects an extended (trans form) conjugated chain, is essential to the inhibition. Compared with the structure of other kinds of inhibitors, a presumable basic structure for inhibiting the enzyme was generated.

Forty-five condensation products of furan-, pyrrole-, and N-methyl pyrrole-alpha-carboaldehyde with N4-3-or 4-substituted phenyl semicarbazides and thiosemicarbazides were designed and synthesized to optimize the antiulcer activity. Quantitative structure-activity relationships reveal that in the series of semicarbazones increase in hydrophobicity of molecules and introduction of electron-repelling groups onto the phenyl ring raise the antiulcer activity; Generally, the activity of semicarbazones is higher than that of the corresponding thiosemicarbazones. The large spans between activity and toxicity of compounds No. 17 and 30 led to further investigation of pharmacological actions.

The anti-virus activity of GPS has been investigated in vitro using L-929 and FL cell line infected with 7 kinds of DNA or RNA virus, and the mechanism by which GPS exhibits the anti-virus activity has been studied. The results show that GPS may inhibit the growth of VSV, AdVIII, HSV-1 or VV and CPE is also suppressed by GPS for protecting culture cell from virus infection.

Twenty-eight condensation products of heterocycle-alpha-carboaldehydes with N-aminooxazolidones, semicarbazides, thiosemicarbazides, aminoguanidines, aromatic hydrazides and benzoxycarbonyl hydrazide were synthesized so as to deduce the antiulcer pharmacophore or fragment of furazolidone(I), the prototype, which shows therapeutic efficacy for patients with gastric ulcer. Analysis of the SAR of the compounds indicate that the substitution of furan, thiophene, pyrrole and N-methyl pyrrole rings for the 5-nitrofuran and the cleavage of the oxazolidone ring obtain the activity to some extent. The necessary electronic density of carbonyl group of compounds is of importance. A lead structure, therefore, is derived for further optimization.