Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.

OBJECTIVE: To observe the impact of indirect moxibustion with Taiyi moxa stick on pain severity and the quality of life in the patients with back myofascitis, and evaluate its clinical effect and safety. METHODS: Seventy-two patients with back myofascitis were randomly divided into an observation group (36 cases, 1 cases dropped out) and a control group (36 cases, 3 cases dropped out). Three to six ashi points were selected using acupoint diagnosis methods. In the observation group, the indirect moxibustion with Taiyi moxa stick was operated at the ashi points, once every other day, three times a week. In the control group, the topical treatment with diclofenac sodium gel was given at ashi points, three times daily. The treatment was delivered consecutively for 2 weeks in the two groups. The scores of visual analogue scale (VAS) and the short-form McGill pain questionnaire (SF-MPQ) were recorded before treatment, after 1 and 2 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit) in the two groups separately. The difference value between VAS score after 2 weeks of treatment and that before treatment was taken as the primary outcome. The SF-36 score was observed before treatment, after 2 weeks of treatment and during the follow-up visit, and the safety was evaluated in the two groups. RESULTS: The difference value of VAS scores was (-4.57±1.50) points and (-2.40±1.31) points in the observation group and the control group, respectively, the reduction of the score in the observation treatment was larger than that of the control group (P<0.001). After 1 and 2 weeks of treatment and during the follow-up visit, VAS and SF-MPQ scores were reduced when compared with those before treatment (P<0.05) in the two groups, and VAS and SF-MPQ scores in the observation group were lower than those in the control group (P<0.05). In the follow-up visit, VAS and SF-MPQ scores in the observation group were dropped in comparison with those after 1 week of treatment (P<0.05), and these scores in the control group were elevated compared with those after 2 weeks of treatment (P < 0.05). After 2 weeks of treatment and during the follow-up visit, the score of each dimension and total score of SF-36 scale were increased in comparison with those before treatment in the observation group (P<0.05); and the scores of the dimensions except that of mental health of SF-36 scale were elevated in the control group (P<0.05). During the follow-up visit, in the control group, the scores of physical functioning, bodily pain, general health and role emotional were elevated when compared with those before treatment (P<0.05). After 2 weeks of treatment and during the follow-up visit, the score of every dimension and total score of SF-36 scale in the observation group were higher than those in the control group (P<0.05). During the follow-up visit, the score of bodily pain was increased when compared with that after 2 weeks of treatment in the observation group (P<0.05), while the scores of bodily pain and vitality were dropped in the control group (P<0.05). No adverse event happened in the two groups. CONCLUSION The indirect moxibustion with Taiyi moxa stick effectively reduces pain severity and improves the quality of life in the patients with back myofascitis. This therapy presents the superior and persistent effect compared with topical application of diclofenac sodium gel.
Humans ; Female ; Male ; Moxibustion ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Young Adult ; Aged ; Quality of Life ; Myofascial Pain Syndromes/therapy*

Objective:To evaluate the expression of amphiregulin(AREG)and interleukin-10(IL-10)in tissues and peripheral blood from pa-tients with cervical cancer(CC)and to explore their relationship with patient prognosis.Methods:Cervical cancer tissues of 40 cervical can-cer patients admitted to The First Affiliated Hospital of Xinjiang Medical University from Jan 2017 to Dec 2018 were collected as the cervical cancer group,and the cervical tissues of 30 patients with negative screening results of uterine fibroids were selected as the control group.Immunohistochemistry(IHC)was performed to compare AREG and IL-10 expression between the two groups.Serum samples from 100 patients with CC(cervical cancer group)and 60 normal healthy individuals(control group)admitted during the same period were ana-lyzed for AREG and IL-10 expression using enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to evaluate the relationship between AREG and IL-10.The 100 patients with cervical cancer were assigned into survivor(80 patients)and deceased(20 patients)groups.A Kaplan-Meier plot was used to analyze the relationship between AREG and IL-10 expression and the survival rates among patients with CC.Binary Logistic regression and receiver operating characteristic curve(ROC)analyses were performed to evaluate prognostic factors.Results:IHC results indicated that AREG and IL-10 were highly expressed in CC tissues compared to normal tissues(P<0.05).ELISA results revealed significantly elevated serum levels of AREG and IL-10 in cancer patients(P<0.000 1).Pearson correlation ana-lysis showed that AREG correlated positively with IL-10(P<0.05,r=0.593 6).Binary Logistic regression analysis identified AREG,IL-10,and lymph node metastasis as independent risk factors impacting survival of patients with CC(all P<0.05).ROC curve analysis showed AREG and IL-10 had high predictive value for survival(AUC=0.897 and 0.874,respectively).Conclusions:Increased AREG and IL-10 expression in tissues and serum of patients with CC suggest that AREG and IL-10 are closely related with the occurrence and progression of the disease.These biomarkers hold significant clinical value for predicting the prognosis of patients with CC.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Objective:To investigate the expression of the novel immune checkpoint SIGLEC9 and SIGLEC9+T cells in cervical cancer and its clinical correlation.Methods:A total of 132 paraffin-embedded specimens of cervical tissue from patients with cervical cancer who under-went surgical treatment or pathological biopsy at The First Affiliated Hospital of Xinjiang Medical University from May 2022 to October 2023 were included for study.In addition,58 paraffin-embedded specimens of normal cervical tissue from patients with benign uterine leiomyomas who underwent total uterine excision during the same period were selected as normal controls.Furthermore,108 peripheral blood samples from patients with cervical cancer who underwent surgical treatment or pathological biopsy were collected for study,and 86 peripheral blood samples from healthy individuals during the same time period were selected as controls.Bioinformatics technology,im-munohistochemical(IHC)staining,flow cytometry,and double immunofluorescence(IF)staining were used to assess the expression of SIGLEC9 and SIGLEC9+T cells in cervical cancer,followed by correlation analysis with clinical indicators.Results:The bioinformatics,IHC,and double IF staining results showed that SIGLEC9 and SIGLEC9+T cells were highly expressed in cervical cancer tissues(P<0.05).The flow cyto-metry results showed that SIGLEC9+CD4+T and SIGLEC9+CD8+T cells were increased in the peripheral blood of patients with cervical cancer(P<0.05).SIGLEC9 expression correlated with tumor size,FIGO stage,lymph node metastasis,and human papillomavirus(HPV)infection(P<0.05).Conclusions:The novel immune checkpoint SIGLEC9 was highly expressed in cervical cancer tissues,and SIGLEC9+T cells infiltrated cervical cancer tissues.In vitro cell experiments showed that SIGLEC9 affects T cell function.In summary,SIGLEC9 provides a novel research direction for understanding the immune escape mechanism of cervical cancer and a novel therapeutic target for cervical cancer immuno-therapy.

Objective:To evaluate the expression of amphiregulin(AREG)and interleukin-10(IL-10)in tissues and peripheral blood from pa-tients with cervical cancer(CC)and to explore their relationship with patient prognosis.Methods:Cervical cancer tissues of 40 cervical can-cer patients admitted to The First Affiliated Hospital of Xinjiang Medical University from Jan 2017 to Dec 2018 were collected as the cervical cancer group,and the cervical tissues of 30 patients with negative screening results of uterine fibroids were selected as the control group.Immunohistochemistry(IHC)was performed to compare AREG and IL-10 expression between the two groups.Serum samples from 100 patients with CC(cervical cancer group)and 60 normal healthy individuals(control group)admitted during the same period were ana-lyzed for AREG and IL-10 expression using enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to evaluate the relationship between AREG and IL-10.The 100 patients with cervical cancer were assigned into survivor(80 patients)and deceased(20 patients)groups.A Kaplan-Meier plot was used to analyze the relationship between AREG and IL-10 expression and the survival rates among patients with CC.Binary Logistic regression and receiver operating characteristic curve(ROC)analyses were performed to evaluate prognostic factors.Results:IHC results indicated that AREG and IL-10 were highly expressed in CC tissues compared to normal tissues(P<0.05).ELISA results revealed significantly elevated serum levels of AREG and IL-10 in cancer patients(P<0.000 1).Pearson correlation ana-lysis showed that AREG correlated positively with IL-10(P<0.05,r=0.593 6).Binary Logistic regression analysis identified AREG,IL-10,and lymph node metastasis as independent risk factors impacting survival of patients with CC(all P<0.05).ROC curve analysis showed AREG and IL-10 had high predictive value for survival(AUC=0.897 and 0.874,respectively).Conclusions:Increased AREG and IL-10 expression in tissues and serum of patients with CC suggest that AREG and IL-10 are closely related with the occurrence and progression of the disease.These biomarkers hold significant clinical value for predicting the prognosis of patients with CC.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Objective:To explore the relationship between drug resistance occurrence and the distribution pattern of polymorphic loci in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) treated with highly active anti-retroviral therapy (HAART).Methods:HAART-failed HIV/AIDS patients who successfully amplified the gene sequences of the pol region between June 2015 and December 2021 from 16 prefecture-level administrative regions in Yunnan Province were included.The resistant sequences were classified using the human immunodeficiency virus (HIV) basic local alignment search tool (BLAST) and validated through MEGA 6.0, and the obtained sequences were submitted to the Stanford University HIV Drug Resistance Database to identify drug resistance loci. The distribution of polymorphic loci was analyzed across patients exhibiting varying degrees of drug resistance, different treatment regimens and distinct HIV-1 subtypes.Changes of the frequencies of polymorphic loci in patients with different degrees of drug resistance were analyzed using trend chi-square test. Statistical comparisons and further paired comparisons were performed using chi-square test.Results:Gene sequences were amplified from 1 453 patients, and the resistance testing results showed 954 sensitive, 224 potentially or low resistant, 189 moderately resistant, and 86 highly resistant patients. The frequencies of mutations I15V, L19I, D60E in the HIV-1 protease region (PR region) and E36A, T39D, S48T mutations in the HIV-1 reverse transcriptase region (RT region) showed a decreasing trend as the degree of HIV-1 resistance escalated ( χ2trend=19.86, 9.16, 13.66, 37.64, 18.44 and 40.86, respectively, all P<0.01). Conversely, the mutations V77I in the PR region and K122E in the RT region showed an ascending trend ( χ2trend=12.19 and 10.03, respectively, both P<0.01). Distinct treatment groups, namely zidovudine (AZT)+ lamivudine (3TC)+ lopinavir/ritonavir (LPV/r), AZT+ 3TC+ efavirenz (EFV), AZT+ 3TC+ nevirapine (NVP), and tenofovir (TDF)+ 3TC+ EFV, were examined. Statistically significant differences in the frequencies of mutations E35D, M36I, and D60E in the PR region, as well as S48T, K122E, and R211K in the RT region, were observed among these treatment groups ( χ2=22.46, 9.32, 14.46, 26.85, 18.92 and 24.26, respectively, all P<0.05). In paired comparisons, AZT+ 3TC+ LPV/r group displayed higher frequencies of E35D, M36I, and D60E mutations, the AZT+ 3TC+ EFV group showed a higher frequency of S48T mutation, the AZT+ 3TC+ NVP group showed a higher frequency of K122E mutation, and the TDF+ 3TC+ EFV group exhibited a higher frequency of R211K mutation, all with statistically significant differences (all P<0.008). The differences in the frequencies of T12S, I15V, L19I, M36I, V77I, L89M in the PR region and E53D, I135V, S162C, R211K, K277R in the RT region among circulating recombinant form (CRF)08_BC, CRF07_BC and CRF01_AE subtype group were statistically significant ( χ2=693.60, 712.51, 798.11, 434.85, 386.91, 657.78, 932.58, 409.21, 344.39, 469.44 and 260.48, respectively, all P<0.001). In paired comparisons, the frequencies of T12S, I15V, L19I, E53D, I135V, S162C and R211K in CRF08_BC subtype, the frequencies of V77I and K277R in CRF07_BC subtype, and the frequencies of M36I and L89M in CRF01_AE subtype were higher than those in the other two groups, and the differences were all statistically significant (all P<0.017). Conclusions:The polymorphic loci resulting from HIV-1 HAART failure show different distribution patterns across various degrees of drug resistance, treatment regimens and HIV-1 subtypes.These loci demonstrate both specific and shared characteristics. It is necessary to enhance the surveillance of select polymorphic loci.

Objective To investigate the distribution of chronic disease and geriatric syndrome in hospitalized elderly patients with multimorbidity by chronic disease investigation and comprehensive geriatric assessment.Methods A total of 176 patients aged ≥60 years admitted into the geriatric department in our hospital were selected,and demographic factors were collected.Their chronic diseases and geriatric syndrome were recorded.The comprehensive geriatric assessment was consummated,and the biochemical indicators for chronic disease and geriatric syndrome were detected.Results All patients suffered from two or more kinds of chronic diseases.The top three most common diseases were hypertension (112 cases),diabetes (94 cases),and respiratory diseases (73cases).The sum of chronic diseases kinds were ≥3 in 137 patients,≥4 in 78 patients,≥5 in 40 patients.The amount of chronic diseases showed an increased tendency along with ageing.Totally 175 patients had more than one geriatric syndrome,the top three most common types were frailty and prefrailty(133 cases),visual impairment (117 cases),impaired daily activities (107 cases).There were significant differences in the number of geriatric syndrome among different age groups(x2 =16.989,P ＜ 0.001).Spearman analysis showed that the number of patients with geriatric syndrome were positively correlated with age(r =0.307,P＜0.001).Conclusions The prevalence of chronic disease and geriatric syndrome is high in hospitalized elderly patients with multimorbidity,which is increased with aging.We should pay attention to the screening of chronic disease and geriatric syndrome in multimorbid elderly patients