Objective:To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) .Methods:This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate.Results:(1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions:Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

The MADS-box gene family is a very important transcriptional regulator gene, which plays a role in the whole growth and development process of plants. The APETALA1 (AP1) gene is considered to play an important regulatory role in the transformation of plant flowering, but also to control the characteristic development of floral organs. Lonicera macranthoides is used as medicine with dry buds and early flowers. Therefore, studying the potential mechanism of AP1 gene in regulating flower organ development can provide a basis for improving its medicinal value by molecular means. To explore the potential mechanism of the AP1 gene in the regulation of floral organ development in L. macranthoides, the full-length cDNA of the AP1 was cloned by reverse transcription PCR (RT-PCR) and named LmMADS4. The results show that the CDS of the LmMADS4 gene is 729 bp and encodes 242 amino acids, and the LmMADS4 protein contains no signal peptide and no transmembrane structure, which is an unstable hydrophilic protein. Through homologous sequence alignment and phylogenetic analysis, LmMADS4 and L. japonica MADS27 protein cluster into one class and are closely related. Finally, the expression pattern and protein interaction pattern of LmMADS4 were analyzed by real-time reverse transcription-PCR (qRT-PCR) and yeast two-hybrid technology. The qRT-PCR showed that LmMADS4 gene was differentially expressed in the stems, leaves and flower bud at different developmental stages, including bud type variety Longhua and common variety Baiyun; and LmMADS4 gene was highly expressed in the flower buds, and with the development of flower buds, LmMADS4 gene was continuously up-regulated in the flower bud variety Longhua, however, the expression level of LmMADS4 in the Baiyun terminal flower bud was lower than that in the late flower bud, but the difference was not significant. The yeast two-hybrid results showed that the bait vector pGBKT7-LmMADS4 was not toxic to yeast strains and had no self-activating activity. LmMADS4 protein interacted with LmSVP1, LmSVP3 and LmSOC1s proteins. This study can provide a theoretical basis for exploring the mechanism of long flower bud stage and corolla non-unfolding at the molecular level and variety improvement of L. macranthoides.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

MADS-box protein family are important transcriptional regulatory factors in plant growth and development. The AGAMOUS 12 (AGL12) subfamily is believed to play an important regulatory role in the process of plant flowering transition. To explore the potential mechanism of AGL12 subfamily involved in regulating the flower development of Lonicera macranthoides, quantitative real-time polymerase chain reaction (qRT-PCR), prokaryotic expression and yeast two-hybrid techniques were used to analyze the expression pattern, protein expression, and protein-protein interaction pattern of LmAGL12 based on transcriptome data. The results showed that the LmAGL12 gene contains a 603 bp open reading frame (ORF), encoding 200 amino acids, and the encoded protein was stable and hydrophilic without a transmembrane region and signal peptide. Through homologous sequence alignment and phylogenetic analysis, it was confirmed that LmAGL12 protein belongs to the MADS-box protein family and is closely related to the AGL12 protein of Heracleum sosnowskyi and Daucus carota subsp. sativus. The LmAGL12 gene was cloned into prokaryotic expression vector pET-28a and the recombinant constructs were transformed into Escherichia coli BL21 (DE3), which inducing the target protein successfully. The yeast two-hybrid results showed that LmAGL12 protein interacts with LmSVP protein, LmSOC1 protein and LmAP1 protein, respectively. The qRT-PCR results showed that LmAGL12 gene were differentially expressed in different development stages of flower bud, stem, and leaves of 'Longhua' and 'Baiyun' in L. macranthoides. The LmAGL12 gene showed the highest expression level in the middle stage of the 'Longhua' floral bud; For the 'Baiyun' variety, the relative expression level of LmAGL12 gene is the highest in the stem. This study cloned the LmAGL12 gene in L. macranthoides and analyzed it expression for the first time, enriching the research on flower organ development and providing a research basis for further exploring the molecular mechanisms of long bud stage and non-unfolded corolla in L. macranthoides, as well as for variety improvement.

Objective:To observe the effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in patients with knee osteoarthritis(KOA)due to wind-cold-dampness Bi-impediment. Methods:A total of 101 patients with KOA due to wind-cold-dampness Bi-impediment were divided into an acupuncture-medication group and a Chinese medication group using the random number table method.Fifty cases in the Chinese medication group took oral Fang Feng Xi Bi Tang for treatment,and 51 cases in the acupuncture-medication group received additional warming triple needling therapy.The symptom score of traditional Chinese medicine(TCM),inflammatory factor levels,and motor function of the knee joint were compared before and after treatment.The clinical efficacy was also compared between the two groups after treatment. Results:Three cases in the acupuncture-medication group and 2 cases in the Chinese medication group dropped out during the study,and the two groups each had 48 cases being included in statistical analysis ultimately.The total effective rate was 95.8%in the acupuncture-medication group,higher than 79.2%in the Chinese medication group,and the between-group difference was statistically significant(P<0.05).After treatment,the TCM symptom score dropped in both groups(P<0.05)and was lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β dropped after the intervention in both groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The scores of knee pain intensity,knee joint stiffness,and diurnal functioning decreased after treatment in the two groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05). Conclusion:Warming triple needling plus Fang Feng Xi Bi Tang can reduce inflammatory responses,improve daily functioning ability,and enhance the quality of life in patients with KOA due to wind-cold-dampness Bi-impediment.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Objective: To investigate the prevalence trend of high normal blood pressure and elevated blood pressure in children and adolescents aged 7 to 17 years in China from 2010 to 2019. Methods: Students aged 7-17 years were selected from the Chinese National Survey on Students' Constitution and Health from 2010 to 2019. High normal blood pressure and elevated blood pressure were determined according to the "Reference of screening for elevated blood pressure among children and adolescents aged 7-18 years" (WS/T 610-2018). The Chi-square test was performed to determine whether there was a difference in the prevalence of high normal blood pressure and elevated blood pressure by gender, residence and age group. Results: In 2019, the prevalence of high normal blood pressure in children and adolescents aged 7-17 years was 15.3% (29 855/195 625), which was higher in boys (20.2%, 19 779/97 847) and rural areas (15.4%, 15 066/97 567) than that in girls (10.3%, 10 076/97 778) and urban areas (15.1%, 14 789/98 058), respectively (all P<0.05). The prevalence of elevated blood pressure was 13.0% (25 377/195 625), which was higher in girls (13.2%, 12 925/97 778) and rural areas (14.1%, 13 753/97 567) than that in boys (12.7%, 12 452/97 847) and urban areas (11.9%, 11 624/98 058) (all P<0.05). From 2010 to 2019, the prevalence of high normal blood pressure showed an increasing trend, with an annual average growth rate from 1.14% to 3.18%. The overall prevalence of elevated blood pressure also showed an increasing trend from 2010 to 2019 but decreased in 2014. The annual average growth rate of elevated blood pressure was-1.07% from 2010 to 2014 and 9.33% from 2014 to 2019. About 17 provinces had an increasing trend in the prevalence of elevated blood pressure from 2010 to 2014, and 22 provinces with an increasing trend from 2014 to 2019. There were obvious regional differences in the annual average growth rate of the prevalence of high normal blood pressure and elevated blood pressure. The regions with the highest annual average growth rate of the prevalence of high normal blood pressure were the Northeast (5.47%) from 2010 to 2014 and the Western region (5.21%) from 2014 to 2019. For elevated blood pressure, the Northeast had the highest annual average growth rate from 2010 to 2014 (12.35%), while the Central (15.79%) and Western (12.87%) had the highest growth rate from 2014 to 2019. Conclusion: From 2010 to 2019, the prevalence of high normal blood pressure and elevated blood pressure in Chinese Han children and adolescents aged 7 to 17 shows an increasing trend, with regional disparities.

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.