Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve^® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve^® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve^® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve^® system.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Prospective Studies ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome

ObjectiveTo explore the effect and mechanism of Lactobacillus paracasei （Lpa） on the prevention of atherosclerosis. MethodsEight-week-old male ApoE^-/- mice were used to establish the atherosclerotic model， and the mice were randomly divided into three groups： ① normal chow control group： ApoE^-/- + normal chow diet （n=10）； ② model group： ApoE^-/- + western diet + PBS （n=10）； ③ Lactobacillus paracasei intervention group： ApoE^-/- + western diet + Lactobacillus paracasei （n=10）. followed by histological evaluations of atherosclerotic lesion in aorta. Immunofluorescence analysis was used to measure the cholesterol accumulation and cholesterol uptake of peritoneal macrophages. Western blot was used to measure the protein expression level of class A scavenger receptor （SR-A） and class B scavenger receptor （CD36）. ResultIntervention of Lactobacillus paracasei can significantly suppress the formation of atherosclerotic plaque in ApoE^-/- mice， reduce the inflammatory reaction of arterial blood vessels， inhibit the lipid accumulation and cholesterol uptake of macrophages， and reduce the protein expression of SR-A. ConclusionsLactobacillus paracasei may protect against atherosclerosis by preventing the inflammation of arterial blood vessels and the formation of foam cells by reducing the protein expression of SR-A.

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Cancer, Regional Perfusion ; Colorectal Neoplasms/therapy* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures ; Humans ; Hyperthermia, Induced ; Hyperthermic Intraperitoneal Chemotherapy ; Peritoneal Neoplasms/drug therapy* ; Prognosis ; Randomized Controlled Trials as Topic ; Survival Rate

Objective:To investigate the effect of Saposhnikoviae Radix on Tongxie Yaofang in regulating water metabolism and 5-serotonin（5-HT） signal system in diarrhea type irritable bowel syndrome（IBS-D）rats. Method:The 40 IBS-D SD rats were randomly divided into model group, Tongxie Yaofang wituout Saposhnikoviae Radix group (26 g·kg^-1), Tongxie Yaofang decoction group (30 g·kg^-1), Tongxie Yaofang with double Saposhnikoviae Radix group (34 g·kg^-1),another 10 normal SD rats were selected as the normal group.Except for normal group, the rats in other groups were separated from their mothers and induced by acetic acid to establish D-IBS model. These rats in the each group were administered with corresponding drugs for 14 days. The diarrhea indexs and the water contents of the feces were observed and calculated. The Na⁺-K⁺-ATPase activities in the intestinal mucosa were detected by micro method. The contents of 5-HT were detected by enzyme linked immunosorbent assay (ELISA). The activities of monoamine oxidase A (MAO-A) were detected by chemiluminescence method. The expressions of aquaporin 4 (AQP4) in colon were detected by immunohistochemistry. Protein expression levels of HT receptor 3 (5-HT₃R), HT receptor 4 (5-HT₄R) and serotonin transporter (SERT) in hypothalamus and colon were detected by Western blot. Result:Compared with normal group, the fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT₃R were significantly increased in model group (P<0.01), and the activities of Na⁺-K⁺-ATPase, expressions of AQP4, 5-HT₄R and SERT were reduced significantly (P<0.01). Compared with model group, the diarrhea indexs and fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT₃R were significantly decreased in each experimental group, and the activities of Na⁺-K⁺-ATPase, expressions of AQP4,5-HT₄R and SERT were significantly increased(P<0.05，P<0.01),however, there was no significant difference in the expression of 5-HT₃R protein in Tongxie Yaofang wituout Saposhnikoviae Radix group.Compared with Tongxie Yaofang wituout Saposhnikoviae Radix group,the diarrhea index, fecal water content, 5-HT content, MAO-A enzyme activity, and protein expression of 5-HT₃R were significantly decreased in Tongxie Yaofang group and Tongxie Yaofang with double Saposhnikoviae Radix group(P<0.05，P<0.01), and the activity of Na⁺-K⁺-ATPase and protein expression of SERT were significantly increased(P<0.05，P<0.01). Conclusion:Saposhnikoviae Radix can enhance the effects of Tongxie Yaofang on improving the water metabolism of rats with IBS-D and regulating the multi-target of 5-HT signaling system, further confirming the synergistic effect of Saposhnikoviae Radix.