Objective:To optimize the preparation process of Qinggan Liangxue Granules.Methods:The L 9 (3 4) orthogonal experimental design was used to investigate the effects of water addition, extraction time and extraction times on the extraction process of Qinggan Liangxue Granules by taking the transfer rate of astilbin and paeoniflorin as the indexes, so as to screen the optimal extraction process. The evaluation indexes of granule molding rate, water content, solubility and fluidity were used to compare the effect of finished products under different ratios of excipients and granulation conditions. Results:The optimal extraction process was to add 10 times the amount of water reflux extraction twice, each time 1.5 h; using wet granulation, the ratio of dry paste powder to base material was 4:1 ( m/ m), and the wetting agent was 95% ethanol. Conclusion:The preparation process of Qinggan Liangxue Granules is stable and feasible, which lays a foundation for further research and development and quality control.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To investigate the efficacy and safety of anlotinib combined with whole brain radiation therapy in the treatment of driver gene mutation-negative non-small cell lung cancer (NSCLC) patients with multiple brain metastases.Methods:Forty-two driver gene mutation-negative NSCLC patients with multiple brain metastases who were admitted to Shaoxing People's Hospital from March 2018 to March 2022 were included. Among them, 21 patients in the anlotinib combined with whole brain radiation therapy group were enrolled from a prospective single-arm study (clinical trial registration number: ChiCTR1900027769), and the patients in the whole brain radiation therapy-alone group were enrolled from a concurrent retrospective study, and after 1∶1 propensity score matching, a total of 21 patients were finally included. The intracranial objective response rate (iORR), intracranial disease control rate (iDCR), intracranial progression-free survival (iPFS), overall survival (OS), and adverse events were compared between the two groups.Results:Among 21 patients in the arotinib combined with whole brain radiation therapy group, there were 1 case (4.8%) of complete remission (CR), 13 cases (61.9%) of partial remission (PR), 6 cases (28.6%) of stable disease (SD), and 1 case (4.8%) of progressive disease (PD). Among 21 patients in the whole brain radiation therapy-alone group, there were 0 case of CR, 10 cases (47.6%) of PR, 7 cases (33.3%) of SD, and 4 cases (19.0%) of PD. The iORR was 66.7% (14/21) and 47.6% (10/21) in the anlotinib combined with whole brain radiation therapy group and whole brain radiation therapy-alone group, respectively ( P = 0.212), and the iDCR was 95.2% (20/21) and 81.0% (17/21), respectively ( P = 0.343). The median iPFS time was 10.4 and 5.3 months in the anrotinib combined with whole brain radiation therapy group and the whole brain radiation therapy-alone group, respectively, and the difference in iPFS between the two groups was statistically significant ( P = 0.049); the 1-year OS rate was 50.5% and 39.5%, and the 2-year OS rate was 29.9% and 26.3%, respectively, with the median OS time of 13.4 and 6.6 months, respectively. The difference in OS between the two groups was not statistically significant ( P = 0.452). The most common treatment-related adverse effects in the anlotinib combined with whole brain radiation therapy group were loss of appetite (13/21, 61.9%), hypertension (11/21, 52.4%), fatigue (10/21, 47.6%), diarrhea (6/21, 28.6%), vomiting (6/21, 28.6%), dizziness (9/21, 42.9%), and headache (8/21, 38.1%). No ≥grade 4 adverse effects were observed, and there were no significant differences in adverse effects between the two groups (all P > 0.05). Conclusions:Anlotinib combined with whole brain radiation therapy can prolong the iPFS time of driver gene mutation-negative NSCLC patients with multiple brain metastases, and it is well-tolerated in terms of safety.

Objective:To investigate the influencing factors of headache degree in migraine patients with patent foramen ovale (PFO).Methods:The clinical data of 124 migraine patients with PFO from January 2013 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. The right-to-left shunt of PFO was assessed by contrast-enhanced transcranial Doppler (c-TCD); the diameter of PFO, length of PFO tunnel and the presence of atrial septal aneurysm (ASA) were detected by transesophageal echocardiography (TEE); the degree of migraine was assessed by headache impact test-6 (HIT-6) scale. The relations between right-to-left shunt volume of PFO, diameter of PFO and degree of migraine were analyzed by Goodman-Kruskal γ test; the relations between the length of PFO tunnel, ASA and degree of migraine were analyzed by Spearman rank correlation analysis.Results:Among the 124 migraine patients with PFO, the c-TCD test result showed that small shunt volume was in 20 cases, medium shunt volume in 31 cases, and large shunt volume in 73 cases. The TEE test result showed that small foramen ovale in 76 cases, medium foramen ovale in 47 cases, and large foramen ovale in 1 case; long tunnel in 57 cases, and short tunnel in 67 cases; without ASA in 91 cases, and with ASA in 33 cases. The HIT-6 score result showed that some influence in 9 cases, significantly influence in 22 cases, and serious influence in 93 cases. The Goodman-Kruskal γ test result showed that right-to-left shunt volume of PFO and diameter of PFO were positive correlation with degree of migraine ( γ = 0.66, P<0.01; γ = 0.38, P<0.05). The Spearman rank correlation analysis result showed that ASA was positive correlation with degree of migraine ( r = 0.18, P<0.05), while the length of PFO tunnel was negative correlation with degree of migraine ( r = -0.23, P<0.05). Conclusions:The right to left shunt amount of PFO, diameter of PFO and the presence of ASA are positive correlation with degree of migraine, while the length of PFO tunnel is negative correlation with degree of migraine.

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Objective:To understand the willingness of contracted residents to renew the family doctor contract service in Shandong Province, and to explore its influencing factors.Methods:From July to August 2020, 1 500 contracted residents in 3cities of Shandong Province were investigated by questionnaire survey.Descriptive statistical analysis, Mann-Whitney U test and binary logistic regression model were used to analyze the contracted residents′ cognition, utilization, satisfaction evaluation and renewal intention of family doctor contract service. Results:1 445 valid questionnaires were obtained, of which 682(47.2%)were willing to renew their contracts.The results of binary logistic regression analysis showed that marital status, educational level, time to see a doctor in contracted institutions, optimism about the development prospect of contracted service policy, whether the proportion of medical insurance reimbursement increased after signing the contract, whether follow-up work was carried out on time, satisfaction with family doctor service attitude and satisfaction with the effect of disease treatment were factors affecting the willingness of contracted residents to renew the contract.Conclusions:The contracted residents in Shandong Province have a high willingness to renew their contracts. On the basis of consolidating and improving the policy cognition and confidence of the contracted residents, we should actively optimize and improve the contracted service quality, ensure the sense of service access of contracted residents, and continuously and effectively realize the comprehensive promotion of the contracted services of family doctors.

Objective: To investigate the dose-response relationship between hemoglobin concentration and preterm birth, during pregnancy. Methods: With Zhuang ethnicity, a total of 12 780 pregnant women and their infants that admitted to Wuming、Pingguo、Jingxi、Debao、Longan and Tiandong hospitals, were recruited, in Guangxi Zhuang Autonomous Region, from January 2015 to December 2017. Non-conditional logistic regression method was used to analyze the effect of anemia on preterm birth during pregnancy. Dose-response relationship between hemoglobin concentration and preterm birth was explored, using the restrictive cubic spline model. Results: After excluding 2 053 pregnant women with hypertension or aged 35 years and over, results from the non-conditional logistic regression analysis showed that the risk of preterm birth in the anemia group was 1.29 times (OR=1.29, 95%CI: 1.04-1.59, P=0.019) of the non-anemia group in the first trimester. Data from the restricted cubic sample showed that there appeared nonlinear "L" dose-response relationship between hemoglobin concentration and preterm birth in the first trimester and "U" shape in the third trimester (non-linearity test P<0.001). Conclusion There appeared nonlinear dose-response relationship between the hemoglobin concentration and preterm birth, both in the first and third trimesters.

Objective: To investigate the association between the preterm birth and low birth weight and parental thalassemia. Methods: Pregnant women and their husbands receiving prenatal examination in local hospitals or maternal and child health centers in Jingxi and Debao in Guangxi from January to December 2017 were selected as study subjects. A total of 758 pregnant women with pregnancy outcomes and their husbands, who were both or alone diagnosed with thalassemia through thalassemia gene detection, were selected as case group and 758 pregnant women with pregnancy outcomes and their husbands, who were negative in thalassemia gene detection and hemoglobin electrophoresis test were selected as control groups. The case group were further divided into mother group, father group and both mother and farther group. Clinical and pregnancy outcome data of the study subjects were collected for the analysis on the association between parental thalassaemia and preterm birth or low birth weight by the independent sample t test, χ² test and Cox regression analysis. Results: The incidence of preterm birth in case group and control group was about 6.5% and 1.6% and the incidence of low birth weight in case group and control group was about 7.3% and 0.8%. After adjusting for possible confounding factors, Cox regression analysis results showed that mother suffering from thalassemia (aRR=3.45, 95%CI: 1.35-8.81, P=0.010), fathers suffering from thalassemia (aRR=4.93, 95%CI: 2.16-11.21, P<0.001) and both mother and farther suffering from thalassemia (aRR=5.13, 95%CI: 2.62-10.04, P<0.001) were associated with preterm birth. Mother suffering from thalassemia (aRR=12.98, 95%CI: 4.91-34.30, P<0.001), fathers suffering from thalassemia (aRR=9.40, 95%CI: 3.40-25.95, P<0.001) and both mother and farther suffering from thalassemia (aRR=10.74, 95%CI: 4.44-26.00, P<0.001) were associated with low birth weight. The newborn whose parent all suffered from thalassemia had higher risks for preterm birth (χ²=22.72, P<0.001)and low birth weight (χ²=34.03, P<0.001) compared with those only with mother or father suffering from thalassemia. Conclusion Parental thalassaemia, including both sides and single side, might increase the risks of preterm birth and low birth weight for newborn, and the risks might be higher in newborn with both mother and father suffering from thalassaemia.

Objective To explore the risk factors of hidden blood loss after UKA.Methods A retrospec-tive study was conducted on 273 patients who underwent UKA from January 2015 to December 2016,including 79 males and 194 females,age between 46 to 87 years old,mean age(67.21± 8.23)years old. The clinical data were collected and the blood volume was calculated according to the Nadler formula. The Gross equation was used to calculate the blood loss and the amount of occult blood loss at 3 days after operation. The risk factors were analyzed statistically. Results The volume of hidden blood loss after operation was(75.36 ± 10.21)mL,and the volume of total blood lost after operation was(187.35± 60.31)mL.Sex,BMI and type of prosthesis were risk factors for hidden blood loss after UKA. Conclusions The volume of hidden blood loss after UKA was related to sex, BMI,and type of prosthesis. For the obese and male patients,we should actively take bleeding management and choose the type of prosthesis reasonably.