ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

OBJECTIVE To resolve account discrepancies caused by drug price adjustment in medical institution pharmacy management and reduce the time required for price adjustment. METHODS The problems existing in the drug price adjustment models of domestic medical institutions were investigated， and a drug price adjustment system was developed based on price- invoice synchronization mechanism. The system optimized the drug price adjustment process through batch number matching and real-time monitoring functionalities. The account consistency rate and price adjustment time were evaluated before and after system implementation. RESULTS A drug price adjustment system was successfully developed， featuring an innovative “synchronized entry and exit” mode， batch number matching， real-time monitoring， intelligent automation， and electronic traceability. After implementation， the account consistency rate for Western medicines increased from 86.89% （86.66%， 89.63%） to 100% （100%， 100%） （P＝0.005）， while Chinese patent medicines and herbal medicines maintained a 100% （100%， 100%） account consistency rate. Concurrently， the drug price adjustment time significantly decreased from 6.00 （5.00， 7.00）d to 2.50 （1.50， 3.00） d （P＜ 0.001）. CONCLUSIONS The developed system significantly improves account consistency， shortens price adjustment time， and demonstrates notable innovation and practical utility.

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.
Adolescent ; Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; China ; Humans ; Immunogenicity, Vaccine ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Young Adult

Objective:To investigate the clinical efficacy of radical proximal gastrectomy with esophagogastrostomy and double-tract anastomosis for upper gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 172 patients who underwent radical proximal gastrectomy for upper gastric cancer in Tianjin Medical University Cancer Institute and Hospital from January 2018 to December 2020 were collected. There were 147 males and 25 females, aged from 25 to 81 years, with a median age of 62 years. All the 172 patients underwent digestive reconstruction. Of the 172 patients, 83 cases undergoing esophagogastrostomy were allocated into esophagogastrostomy group, 89 cases undergoing double-tract anastomosis were allocated into double-tract anastomosis group. Patients were performed radical proximal gastrectomy combined with D 1+ lymph node dissection by attending surgeons from department of gastric cancer. The operator decided to adopt esophagogastrostomy or double-tract anastomosis for digestive reconstruction. Observation indicators: (1) surgical situations; (2) follow-up. Follow-up using outpatient examination, telephone interview, and online APP was conducted at postoperative 1 month, once three months within postoperative 2 years, and once six months within postoperative 2-5 years. The questionnaires of reflux esophagitis, gastroscopy and upper gastrointestinal angio-graphy were conducted to evaluate gastroesophageal reflux and anastomotic stenosis up to February 1, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Surgical situations: cases with open, laparoscopic or Da Vinci robotic surgery (surgical method), the number of metastatic lymph node, duration of postoperative hospital stay were 74, 9, 0, 2(range, 0-15), (12±4)days for the esophagogastrostomy group, versus 65, 15, 9, 3(range, 0-28), (11±3)days for the double-tract anastomosis group, respectively, showing significant differences in the above indicators between the two groups ( χ2=10.887, Z=-1.058, t=3.284, P<0.05). (2) Follow-up: 172 patients were followed up for 2-38 months, with a median follow-up time of 13 months. Cases with gastroesophageal reflux and anastomotic stenosis were 58 and 10 for the esophagogastrostomy group, versus 14 and 1 for the double-tract anastomosis group, respectively, showing significant differences in the above indicators between the two groups ( χ2=51.743, 7.219, P<0.05). Conclusions:For upper gastric cancer patients undergoing proximal radical gastrectomy, double-tract anastomosis is more suitable for Siewert type Ⅱ adenocarcinoma of esophagogastric junction in large curvature or lower located tumor. Compared with esophago-gastrostomy, double-tract anastomosis has lower incidence of postoperative gastroesophageal reflux and anastomotic stenosis, without increasing complications.

Gastrectomy with D2 lymph node dissection has become the global standard procedure for locally advanced gastric cancer. Based on the evidence of the clinic trials, postadjuvant chemotherapy after D2 gastrectomy is the current standard strategy. Neoadjuvant chemotherapy can increase the R0 resection rate, but the consensus has not been reached. These trials could lead to new evidence for improved treatment of gastric cancer in the near future. This review will summarize recent evidence on the benefits of for locally advanced gastric cancer.

From the two aspects both at home and abroad endowment institutions the elderly family support commonly used assessment tool, this paper introduces the process of development of tools, dimensions, scoring method, and analyze the reliability and validity of the advantages and disadvantages of various assessment tools, aimed at the elderly family support for localization development of our country endowment institutions provide reference for the development and application of assessment tools.

Objective: To evaluate the clinical efficacy of percutaneous tibial nerve electrical stimulation in the treatment of chronic pelvic pain syndrome. Methods: The clinical data of 28 patients with chronic pelvic pain syndrome from January to November 2018 in Dalian Third People′s Hospital were retrospectively analyzed. The patients were treated with percutaneous tibial nerve stimulation. The number of urination in 24 h, number of nocturnal urination, urine volume per urination, quality of life (QOL) score and digital pain intensity score before treatment and after treatment were compared; the patients were followed up for 3 months, and the recurrence and adverse reaction were observed. Results: Compared with those before treatment, the number of urination in 24 h and number of nocturnal urination after treatment were significantly lower: (11.6 ± 6.4) times vs. (20.6 ± 7.8) times and (2.5 ± 1.2) times vs. (5.2 ± 2.6) times, and the urine volume per urination increased significantly: (181.2 ± 65.6) ml vs. (125.4 ± 58.2) ml, the QOL score and digital pain intensity score decreased significantly: (2.6 ± 1.4) scores vs. (5.1 ± 0.8) scores and (2.9 ± 1.3) scores vs. (6.9 ± 1.4) scores, and there were statistical differences (P<0.05). During the follow-up period, none of the patients had recurrent symptoms and obvious adverse reaction. Conclusions Percutaneous tibial nerve stimulation is an effective way to treat chronic pelvic pain syndrome.

Objective: To evaluate the impact of perineural invasion (PNI) on the overall survival (OS) of patients with gastric cancer. Methods: A total of 1,007 patients with gastric cancer who underwent curative resection between January 2011 and December 2012 at the Cancer Institute and Hospital of Tianjin Medical University were enrolled. All the patients were categorized into the following two groups according to the status of PNI: positive group, presence of PNI; and negative group, absence of PNI. Potential prognostic factors and clinical pathological variables correlated with the presence of PNI were analyzed. Results: One hundred and twenty (11.9%) patients had PNI. Multivariate analysis revealed that histology, depth of invasion, and lymphovascular invasion were indepen-dently associated with the presence of PNI. Univariate survival analysis revealed that age, tumor location, Borrmann type, tumor size, curability, TNM stage, type of gastrectomy, tumor deposit, lymphovascular invasion, PNI, preoperative CA19-9 levels, and CEA levels were significant prognostic factors. Gastric cancer patients with PNI had a significantly lower 5-year OS rate than those without PNI (5-year OS: 38.3% versus 66.6%, P<0.001). In the multivariate analysis, age, Borrmann typeⅣ, TNM stage, curability, tumor deposit, and PNI were independent prognostic factors for this population cohort. The strata analysis revealed that PNI merely had a significant im-pact on OS in patients at stagesⅠ,Ⅱ, andⅢa. Conclusions: PNI is an independent prognostic factor in patients with gastric cancer and can be used as a prognostic indicator for gastric cancer patients at stagesⅠ,Ⅱ, andⅢa.

?? [Abstract]? Objective? To construct a prenatal care information platform based on "Five-color Management" to improve the health of pregnant women. Methods? From January to February 2018, we selected 152 pregnant women under perinatal care in obstetrical outpatient department and 138 medical workers in obstetrical department at three Class Ⅲ hospitals in He'nan as subjects. Platform contents and functions were determined by literature review, questionnaire survey and expert group meeting. Questionnaire survey adopted the method of convenience sampling. Results? The recovery rate of the pregnant women version and doctor-nurse version of platform content and function demands questionnaire was 97.37% and 98.57% respectively. The plan first draft was developed based on questionnaire survey. Finally, the platform set three-level management content, five color grade and eight function modules by rounds of expert group meeting. Conclusions? The prenatal care information platform has a strict construction method and highly accords with the demands of pregnant women and doctor-nurse. The platform has a strong operability which realizes the high-efficient management for pregnant women and improves the health of pregnant women.