Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

To date, there is little information about the demography of vasectomy reversal (VR) patients or the factors currently influencing VR effectiveness in China, especially after the universal two-child policy was released in 2015. In this research, demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of China. Meanwhile, a telephone survey of the patients was conducted to collect follow-up information. Eventually, 448 VR cases from the past 13 years were included. The results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy rate. Appropriately statistical methods were used, and all of the protocols were approved by the Ethics Committees of the institutes in this research. The results showed that the annual operation volume of VR quadrupled after the two-child policy was implemented. Nonmicrosurgery and a long duration of vasectomy were significantly associated with a lower patency rate. A follow-up survey showed that the general postoperative pregnancy rate was 27.2%. For female partners over the age of 35 years, the postoperative pregnancy rate showed a more severe decline, but only 35.5% of them had been given a fertility examination before their husbands' VR surgery. Our work revealed that more patients in China have been demanding VR in recent years. High-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by VR. Clinical andrologists should perform a preoperative fertility evaluation of the patients' female partners.
Male ; Pregnancy ; Humans ; Female ; Adult ; Vasovasostomy ; Retrospective Studies ; Vas Deferens/surgery* ; Vasectomy ; China/epidemiology*

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

ObjectiveTo reveal the medication rules of the clinical prescriptions containing Citri Sarcodactylis Fructus， and to provide a basis for the modern clinical application of Citri Sarcodactylis Fructus， the development of health products and the research and development of new drugs. MethodThe clinical prescriptions containing Citri Sarcodactylis Fructus were retrieved from CNKI， Wanfang Data， and VIP， and then a basic database of prescriptions was established via the traditional Chinese medicine inheritance auxiliary platform （V2.5）， IBM SPSS V20， and Excel （Microsoft Office 2016）. The frequency and association rules of the medicines in prescriptions （compatible medicines） and the corresponding syndromes were then mined. ResultThe prescriptions were screened according to the inclusion and exclusion criteria. A total of 458 clinical prescriptions containing Citri Sarcodactylis Fructus were collected， involving 388 Chinese medicines， and the total frequency of medicines reached 6 199. The core compatible medicines （frequency > 130） of Citri Sarcodactylis Fructus included Poria （frequency of 222）， Atractylodis Macrocephalae Rhizoma （217）， Paeoniae Radix Alba （196）， Bupleuri Radix （159）， and Citri Reticulatae Pericarpium （142）. The Citri Sarcodactylis Fructus-compatible medicines with frequency > 49 were selected for further analysis， which included 34 medicines with the cumulative frequency of 3 131 （50.51% of the total frequency）. These medicines mainly have the functions of tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain. They are mainly warm， cold， or mild-natured， taste bitter， sweet， or acrid， and have the tropism in the spleen， liver， stomach， or lung meridians. The association rule analysis demonstrated that 14 medicine combinations were commonly used， and the core combinations were Poria-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Citri Sarcodactylis Fructus， Paeoniae Radix Alba-Citri Sarcodactylis Fructus， Bupleuri Radix-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Poria-Citri Sarcodactylis Fructus， and Citri Reticulatae Pericarpium-Citri Sarcodactylis Fructus. The clinical prescriptions containing Citri Sarcodactylis Fructus were mainly used to treat 52 diseases corresponding to 11 types of traditional Chinese medicine （TCM） syndromes. Three representative syndrome types， including spleen and stomach syndromes， Qi-blood-body fluid syndromes， and gynecological syndromes were selected for further association rule analysis. In the treatment of spleen and stomach syndromes， the core compatible drugs were Atractylodis Macrocephalae Rhizoma， Poria， Paeoniae Radix Alba， Bupleuri Radix， Citri Reticulatae Pericarpium， and Pinelliae Ehizoma， which， together with Citri Sarcodactylis Fructus， formed 25 commonly used medicine combinations （16 combinations composed of 2 medicines and 9 combinations composed of 3 medicines）. In the treatment of Qi-blood-body fluid syndromes， the core compatible drugs were Poria， Paeoniae Radix Alba， Atractylodis Macrocephalae Rhizoma， Astragali Radix， Hordei Fructus Germinatus， and Bupleuri Radix， which， together with Citri Sarcodactylis Fructus， formed 23 common medicine combinations （17 combinations composed of 2 medicines， 5 combinations composed of 3 medicines， and 1 combination composed of 4 medicines）. In the treatment of gynecological syndromes， the core compatible medicines were Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Angelicae Sinensis Radix， Astragali Radix， Cyperi Rhizoma， and Poria， which constituted 25 common medicine combinations （15 combinations composed of 2 medicines and 10 combinations composed of 3 medicines）. ConclusionWe employed the traditional Chinese medicine（TCM） inheritance auxiliary platform to explore the compatibility of Citri Sarcodactylis Fructus-containing clinical prescriptions and the corresponding TCM syndromes， which intuitively showcased the medication rules of Citri Sarcodactylis Fructus. Specifically， Citri Sarcodactylis Fructus was mainly combined with the medicines for tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain to treat different TCM syndromes. While soothing liver， regulating Qi， harmonizing stomach， and relieving pain， the combinations tonify and activate blood， invigorate spleen， and resolve dampness. The findings are of great significance to the rational application of Citri Sarcodactylis Fructus， the development of health food， and the research of new drugs and will bolster the development of Chinese medicine industry.

Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

OBJECTIVE: To compare the clinical effect on intestinal dysfunction of spinal cord injury (SCI) between the comprehensive therapy of moxibustion (moxibustion for opening the governor vessel and regulating the spirit) and rehabilitation training and the simple treatment with rehabilitation training. METHODS: A total of 60 patients with intestinal dysfunction of SCI were randomized into a comprehensive therapy group and a rehabilitation group, 30 cases in each one (3 cases were dropped out in each group). On the base of the routine western medicine treatment and rehabilitation training, the bowel training and rectal function training were provided, once a day in the rehabilitation group. In the comprehensive therapy group, on the base of the treatment as the rehabilitation group, the moxibustion was exerted at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Dazhui (GV 14) and Baihui (GV 20), etc, once a day, 30 min each time. In both groups, the treatment for 4 weeks was as one course and 3 courses of treatment were required. Separately, before treatment, after 4, 8 and 12 weeks of treatment, the scores of neurogenic bowel dysfunction (NBD) and World Health Organization quality of life scale (WHOQOL-BREF) were observed and the clinical effect was evaluated after 12 weeks of treatment. RESULTS: After treatment, the total effective rate was 88.9% (24/27) in the comprehensive therapy group, which was higher than 74.1% (20/27) in the rehabilitation group (<0.05). After 4, 8 and 12 weeks of treatment, NBD scores were all reduced obviously as compared with those before treatment in the two groups (all <0.01). After 8 and 12 weeks of treatment, NBD scores in the comprehensive therapy group were lower than the rehabilitation group (both <0.05). After 4, 8 and 12 weeks of treatment, the scores of all of the domains (psychology, physiology, social relations and environment) in WHOQOL-BREF were higher than those before treatment in the two groups (all <0.01). After 4 weeks of treatment, the scores in the psychology and physiology domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05). After 8 and 12 weeks of treatment, the scores of all of the domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05). CONCLUSION The comprehensive treatment of moxibustion and rehabilitation training achieves the better effect on intestinal dysfunction of SCI than the simple rehabilitation training and greatly improves the quality of life in SCI patients.
Acupuncture Points ; Humans ; Moxibustion ; Quality of Life ; Spinal Cord Injuries ; therapy

We retrospectively reviewed data for 286 patients with varicocele who underwent microsurgical subinguinal varicocelectomy from March 2015 to May 2017 in Shanghai General Hospital (Shanghai, China). In this surgical approach, the testis was delivered, and the gubernacular and external cremasteric veins were stripped. In addition, the spermatic cord was delivered downward with continuous double traction away from the external ring. The remaining procedure was similar to the conventional approach. We followed patients for at least 3 months and evaluated postoperative semen parameters, pain symptoms, and complications. We excluded data for 32 men due to inadequate follow-up (<3 months). Of the remaining 254 patients, 73 had oligoasthenospermia, 121 had nonobstructive azoospermia, and 60 had symptomatic varicoceles. Total progressive sperm counts increased in the oligoasthenospermic patients from a median preoperative value of 9.15 × 10⁶ ml^-1 to 25.33 × 10⁶ ml^-1 (n= 34), and 35.6% (26/73) initially oligoasthenospermic men contributed to unassisted pregnancies. Sperm returned to the ejaculate in 12.4% (15/121) azoospermia patients. In patients with scrotal pain (n = 60), 43 (71.7%) reported complete resolution of pain, 16 (26.7%) reported partial resolution, and 1 (1.7%) reported no change. No patients experienced varicocele recurrence. This double-traction strategy avoids opening the external oblique aponeurosis, and results in less damage and faster recovery. In addition, the stripping strategy eliminates potential damage to the testis caused by the varicose veins. Our results showed that microsurgical subinguinal varicocelectomy using spermatic cord double traction in conjunction with testicular delivery for vein stripping is a safe and effective approach for varicocele repair.
Adolescent ; Adult ; Humans ; Male ; Microsurgery ; Middle Aged ; Retrospective Studies ; Spermatic Cord/surgery* ; Testis/blood supply* ; Treatment Outcome ; Urogenital Surgical Procedures/methods* ; Varicocele/surgery* ; Veins/surgery* ; Young Adult

Non-obstructive azoospermia (NOA), which is defined as the absence of spermatozoa in the ejaculate secondary to impaired spermatogenesis within the testis, may be caused by a variety of etiologies, including varicocele-induced testicular damage, cryptorchidism, prior testicular torsion, post-pubertal mumps orchitis, gonadotoxic effects from medications, genetic abnormalities, chemotherapy/radiation, and other unknown causes currently classified as idiopathic (Cocuzza et al., 2013). The microdissection testicular sperm extraction (micro-TESE) technique involves a meticulous microsurgical exploration of the testicular parenchyma to identify and selectively extract larger seminiferous tubules that carry a higher probability of complete spermatogenesis (Schlegel, 1999). The Cornell group evaluated the efficacy of micro-TESE in 152 NOA patients with an associated history of cryptorchidism. In their series, spermatozoa were successfully retrieved in 116/181 attempts (64%), and the resulting pregnancy rate was 50% with a delivery rate of 38% (Dabaja and Schlegel, 2013). Franco et al. (2016) described a stepwise micro-TESE approach in NOA patients, which was considered to reduce the cost, time, and effort associated with the surgery. Alrabeeah et al. (2016) further reported that a mini-incision micro-TESE, carried through a 1-cm equatorial testicular incision, can be useful for micro-TESE candidates, particularly in patients with cryptozoospermia. We conducted a retrospective study of 20 consecutive NOA patients with a history of orchidopexy from May 2015 to March 2017.
Adult ; Azoospermia/surgery* ; Humans ; Male ; Microdissection/methods* ; Middle Aged ; Orchiopexy ; Retrospective Studies ; Sperm Retrieval