Distribution of Nerve Fibers in Abdominal Wall Endometriosis and Their Clinical Significance.

Objective: This study aimed to explore the distribution of nerve fibers in abdominal wall endometriosis (AWE) and discern their association with pain. Methods: A retrospective case-control study was conducted. The cases comprised 30 patients diagnosed with AWE, while the control group consisted of 17 patients who had undergone laparotomy without any history of endometriosis. We analyzed clinical characteristics and examined the innervation patterns in samples using stains for S-100, neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), neurofilament (NF), and substance P (SP) antibodies. Results: There was a notable increase in the density of S-100, NSE and PGP9.5 immunoreactive nerve fibers and a higher proportion of SP positivity in AWE lesions compared to standard abdominal wall scars (p < 0.05). However, there were no significant differences in the density or proportion of NF-immunoreactive nerve fibers between the cases and the controls. Moreover, no statistically significant correlation was observed between the density of S-100, NSE, PGP9.5, NF, or SP-positive nerve fibers and pain scores. Conclusion: This study demonstrated an increased immunoreactive nerve fiber density located in AWE lesions compared to normal abdominal wall scars. Further high-quality studies are needed to investigate the mechanisms responsible for pain in women with endometriosis.

Amplifying dual-visible-light photoswitching in aqueous media via confinement promoted triplet-triplet energy transfer.

Achieving visible-light photochromism is a long-term goal of chemists keen to exploit the opportunities of molecular photoswitches in multi-disciplinary research studies. Triplet-sensitization offers a flexible approach to building diverse visible-light photoswitches using existing photochromic scaffolds, circumventing the need for sophisticated molecular design and synthesis. Unfortunately, distance-dependence and environment-sensitivity of triplet-excited species remain as key challenges that severely impair sensitization efficiency and limit their practical availability. We present herein a nature-inspired nanoconfinement strategy in which a triplet-sensitized visible-light photoswitch/sensitizer system is assembled into nanoconfined micelles (d ∼ 40 nm). A ca. 10-fold efficiency increase of triplet-triplet energy transfer for photochromism as well as an amplified fluorescence on/off contrast upon bi-directional visible-light excitation (470/560 nm) was achieved in full aqueous media. By virtue of this, the hybrid photoswitchable system is successfully applied for both flash information encryption and multiple dynamic cell imaging assays, further proving its versatility in materials and life science.

Photo-Responsive Hydrogel for Contactless Dressing Change to Attenuate Secondary Damage and Promote Diabetic Wound Healing.

Dressing change is a significant and inevitable process during wound healing. Possible secondary damage caused through dressing removal may impose a great threat on wound recovery, thus resulting in healing delays and ultimately a higher cost of hospitalization. Hence, a non-contact refreshable dressing with an ease of operation is of great desire, especially for chronic wounds where a long-term and repeated dressing change would be performed. Herein, an all-light-operated hydrogel dressing that would achieve a fast and remote-controllable dressing change (30 s for gelation/4 min for dissolution upon light irradiation) for chronic wounds is presented. In a diabetic murine model, substantially improved wound healing within 2-3 weeks is observed due to attenuated secondary damage during repeated dressing changes. Moreover, a promising facilitation of the healing processes of epithelialization, collagen deposition, cell proliferation, and inflammatory regulation is also detected, representing a synergistic effect of the photo-responsive hydrogel dressing for therapeutic efficiency.

Characteristics and Occurrence Scenarios of Staff Exposed to SARS-CoV-2 Omicron in Shanghai Lingang Fangcang Shelter Hospital, CHINA.

Objective: To analyze the characteristics and occurrence scenarios of occupational exposure of staff in the Shanghai Lingang Fangcang Shelter Hospital. Methods: We collected the data of 80 staff with occupational exposure (including doctors, nurses, cleaning, security guards, and maintenance staff) in the Shanghai Lingang Fangcang Shelter Hospital from April 5 to May 20, 2022. The basic information of occupational exposure, factors influencing different occupational exposure types, ways to discover occupational exposure, discovery places of occupational exposure, and specific occurrence scenarios were compiled and analyzed among these data. Results: Occupational exposure mainly occurred in nurses (37, 46.25%), and cleaning (21, 26.25%). After the occurrence of occupational exposure, 20 staff (25%) did not know the occurrence time. Moreover, occupational exposure types were listed from high to low proportion as follows: broken protective clothing (56, 70%), mask loosening or displacement (13, 16.25%), skin exposure (6, 7.5%), and sharp object injuries (5, 6.25%). Occupational exposure was discovered mainly through self-discovery (56, 70%), while other discovery ways were majorly colleague discovery (12, 15%) and infection control supervisor discovery (12, 15%). Furthermore, occupational exposure was discovered principally in the public area (53.75%) and the office area (25%) of the cabin, but the proportion of mask loosening or displacement (38.46%) and skin exposure (50%) was also high in the first unloading area. Broken protective clothing occurred in the following scenarios: scratching while working in the cabin (37, 66.07%) and not knowing its occurrence time (25%). The occurrence scenarios of mask loosening or displacement were mainly not knowing its occurrence time (6, 46.15%), self-discovery (3, 23.08%), and at the time of removal (3, 23.08%). Conclusion: Targeted training and prevention of occupational exposure should be performed to decrease infection risk and ensure staff safety in Fangcang shelter hospitals.

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice.

Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO-) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO- level during DILI in vivo. Therefore, ONOO--activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO--responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO--mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO- concentration changes in living cells. Importantly, in vivo fluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO- in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO- under different pathological conditions.

One-Pot Synthesis of Bioadhesive Double-Network Hydrogel Patch as Disposable Wound Dressing.

Inventions of materials to achieve biocompatibility, bioadhesion, and easy manufacturing are the urgent demand for promoting wound healing in clinical treatment. Hyaluronic acid (HA) is probably the ideal candidate for current dressing materials due to its well-known biocompatibility. However, the unavoidable problem for HA dressings is their inherent low adhesiveness to wounds, which severely impairs their treatment efficacy, especially during body movement. Here, we report a one-pot facile fabrication of hybrid double-network polydopamine-HA (PDA-HA) hydrogel with significantly enhanced adhesiveness compared to the HA hydrogel. Besides the easy manufacturing and promoted effectiveness, the PDA-HA hydrogel could be vacuum-dried to form a patch, further benefitting from the convenience for storage and distribution. When applied on the wound, the PDA-HA patch quickly rehydrated by absorbing exudate and stuck tightly to the wound. The applied PDA-HA patches keep the wounds covered for more than 7 days against strenuous exercise. Thus, mouse full-thickness wounds treated with the PDA-HA patches exhibited increased healing rates, where epithelization was finished within 14 days. Moreover, the hydrogel dressing exhibited promoting effects on vascularization and cell proliferation/migration. Together with the easy manufacturing procedure, good adhesion/adaptation, and promotion of wound healing, the PDA-HA patch holds great potential for future clinical translation.

Green-Light Responsive Perylene Bisimides for Atom-Economic Thiol Generation and Click-Ligation.

Novel methylthiophene/benzo[b]thiophene perylene bisimide thiol-precursors that would generate thiols via a green-light-induced (λexc = 530 nm, φre = 0.33) photorearrangement are presented herein. The "no-wash", photoreleased thiols thus enabled a subsequent thiol-ene click ligation with electron-deficient substrates. Moreover, by virtue of the intrinsic fluorescence evolution from the rearrangement of perylene bisimide scaffolds, the whole process of thiol formation could be self-reported, further potentiating themselves with application versatilities.

The clinical features and long-term surgical outcomes of different types of abdominal wall endometriosis.

PURPOSE: To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. METHODS: In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. RESULTS: Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. CONCLUSION: Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.

Topologically switchable and gated transcription machinery.

Topological barriers control in nature the transcription machinery, thereby perturbing gene expression. Here we introduce synthetically designed DNA templates that include built-in topological barriers for switchable, triggered-controlled transcription of RNA aptamers. This is exemplified with the design of transcription templates that include reversible and switchable topological barriers consisting of a Sr2+-ion-stabilized G-quadruplex and its separation by kryptofix [2.2.2], KP, for the switchable transcription of the malachite green (MG) RNA aptamer, the T-A·T triplex barrier being separated by a fuel-strand for the cyclic triggered transcription of the 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI)-binding aptamer, and the use of a photoactivated cis/trans azobenzene-modified nucleic acid barrier for the switchable "ON"/"OFF" transcription of the MG RNA aptamer. By applying a mixture of topologically triggered templates consisting of the photoresponsive barrier and the T-A·T triplex barrier, the gated transcription of the MG aptamer or the DFHBI-binding aptamer is demonstrated. In addition, a Sr2+-ion/KP topologically triggered DNA tetrahedra promoter-transcription scaffold, for the replication of the MG RNA aptamer, and T7 RNA polymerase are integrated into DNA-based carboxymethyl cellulose hydrogel microcapsules acting as cell-like assemblies. The switchable, reversible transcription of the MG RNA aptamer in a cell-like containment is introduced.

Stepping Out of the Blue: From Visible to Near-IR Triggered Photoswitches.

Light offers unique opportunities for controlling the activity of materials and biosystems with high spatiotemporal resolution. Molecular photoswitches are chromophores that undergo reversible isomerization between different states upon irradiation with light, allowing a convenient means to control their influence over the system of interest. However, a significant limitation of classical photoswitches is the requirement to initiate the switching in one or both directions using deleterious UV light with poor tissue penetration. Red-shifted photoswitches are hence in high demand and have attracted keen recent research interest. In this Review, we highlight recent progress towards the development of visible- and NIR-activated photoswitches characterized by distinct photochromic reaction mechanisms. We hope to inspire further endeavors in this field, allowing the full potential of these tools in biotechnology and materials chemistry applications to be realized.

Recent Advances in Stimuli-Responsive DNA-Based Hydrogels.

Stimuli-responsive DNA-based hydrogels are attracting growing interest because of their smart responsiveness, excellent biocompatibility, regulated biodegradability, and programmable design properties. Integration of reconfigurable DNA architectures and switchable supramolecular moieties (as cross-linkers) in hydrogels by responding to external stimuli provides an ideal approach for the reversible tuning structural and mechanical properties of the hydrogels, which can be exploited in the development of intelligent DNA-based materials. This review highlights recent advances in the design of responsive pure DNA hydrogels, DNA-polymer hybrid hydrogels, and autonomous DNA-based hydrogels with transient behaviors. A variety of chemically and physically triggered DNA-based stimuli-responsive hydrogels and their versatile applications in biosensing, biocatalysis, cell culture and separation, drug delivery, shape memory, self-healing, and robotic actuators are summarized. Finally, we address the key challenges that the field will face in the coming years, and future prospects are identified.

Photoresponsive DNA materials and their applications.

Photoresponsive nucleic acids attract growing interest as functional constituents in materials science. Integration of photoisomerizable units into DNA strands provides an ideal handle for the reversible reconfiguration of nucleic acid architectures by light irradiation, triggering changes in the chemical and structural properties of the nanostructures that can be exploited in the development of photoresponsive functional devices such as machines, origami structures and ion channels, as well as environmentally adaptable 'smart' materials including nanoparticle aggregates and hydrogels. Moreover, photoresponsive DNA components allow control over the composition of dynamic supramolecular ensembles that mimic native networks. Beyond this, the modification of nucleic acids with photosensitizer functionality enables these biopolymers to act as scaffolds for spatial organization of electron transfer reactions mimicking natural photosynthesis. This review provides a comprehensive overview of these exciting developments in the design of photoresponsive DNA materials, and showcases a range of applications in catalysis, sensing and drug delivery/release. The key challenges facing the development of the field in the coming years are addressed, and exciting emergent research directions are identified.

DNAzyme- and light-induced dissipative and gated DNA networks.

Nucleic acid-based dissipative, out-of-equilibrium systems are introduced as functional assemblies emulating transient dissipative biological transformations. One system involves a Pb2+-ion-dependent DNAzyme fuel strand-driven network leading to the transient cleavage of the fuel strand to "waste" products. Applying the Pb2+-ion-dependent DNAzyme to two competitive fuel strand-driven systems yields two parallel operating networks. Blocking the competitively operating networks with selective inhibitors leads, however, to gated transient operation of dictated networks, yielding gated catalytic operations. A second system introduces a "non-waste" generating out-of-equilibrium, dissipative network driven by light. The system consists of a trans-azobenzene-functionalized photoactive module that is reconfigured by light to an intermediary state consisting of cis-azobenzene units that are thermally recovered to the original trans-azobenzene-modified module. The cyclic transient photoinduced operation of the device is demonstrated. The kinetic simulation of the systems allows the prediction of the transient behavior of the networks under different auxiliary conditions.

A crosslinked colloidal network of peptide/nucleic base amphiphiles for targeted cancer cell encapsulation.

The use of peptide amphiphiles (PAs) is becoming increasingly popular, not only because of their unique self-assembly properties but also due to the versatility of designs, allowing biological responsiveness, biocompatibility, and easy synthesis, which could potentially contribute to new drug design and disease treatment concepts. Oligonucleotides, another major functional bio-macromolecule class, have been introduced recently as new functional building blocks into PAs, further enriching the tools available for the fabrication of bio-functional PAs. Taking advantage of this, in the present work, two nucleic base-linked (adenine, A and thymine, T) RGD-rich peptide amphiphiles (NPAs) containing the fluorophores naphthalimide and rhodamine (Nph-A and Rh-T) were designed and synthesized. The two NPAs exhibit distinctive assembly behaviours with spherical (Rh-T) and fibrous (Nph-A) morphologies, and mixing Nph-A with Rh-T leads to a densely crosslinked colloidal network (Nph-A/Rh-T) via mutually promoted supramolecular polymerization via nucleation-growth assembly. Because of the RGD-rich sequences in the crosslinked network, further research on in situ targeted cancer cell (MDA-MB-231) encapsulation via RGD-integrin recognition was performed, and the modulation of cell behaviours (e.g., cell viability and migration) was demonstrated using both confocal laser scanning microscopy (CLSM) imaging and a scratch wound healing assay.

Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study.

BACKGROUND: Adenomyosis (AM) and endometriosis (EM) often coexist. Laparoscopic surgery is one of the main methods for diagnosing and treating these conditions. This study aims to investigate the pregnancy outcomes of women with infertility with both AM and EM after laparoscopic surgery and to identify the relevant associated factors. METHODS: This is a retrospective study involving women with infertility diagnosed with EM and AM. All patients had undergone laparoscopic surgery and were divided into two groups according to their pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected. RESULTS: A total of 226 female patients with infertility diagnosed with both AM and EM underwent laparoscopic surgery. Of these, a total of 176 patients completed follow-up. Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The clinical pregnancy and live birth rates were 67.4 and 55.11%, respectively. One hundred thirty-five patients received in vitro fertilization (IVF), with 70 (51.85%) of these patients having live births. Age, endometrioma size, and uterus size were significantly lower in those who had a successful delivery. There was no statistically significant difference in symptoms, except that those who achieved live birth had a lower rate of anaemia (13.40% vs. 25.32%, p = 0.044). The group that did not proceed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (p < 0.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR: 1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live birth in the multivariable analysis. CONCLUSIONS: Endometriosis and adenomyosis appear to have an adverse effect on pregnancy outcome. These might be related to the size of the uterus and EFI. Obstetricians and gynaecologists should be alert to this potential adverse effect and manage these patients accordingly.

Hysterectomy and bilateral adnexectomy using transvaginal natural orifice transluminal endoscopic surgery: The role of multichannel abdominal PORT and vaginal support ring.

BACKGROUND: Although transvaginal natural orifice transluminal endoscopic surgery (NOTES) is gaining importance, knowledge on transvaginal NOTES procedures in gynecologic practice is limited. OBJECTIVE: We aimed at evaluating the feasibility and safety of performing hysterectomy and bilateral adnexectomy (or bilateral salpingectomy) via transvaginal NOTES using a self-developed multichannel abdominal port and vaginal support ring. STUDY DESIGN: A prospective, single-center, cohort pilot study was conducted from May to December 2017 in patients with benign uterine diseases or endometrial atypical hyperplasia or cervical intraepithelial neoplasia (n = 30) scheduled for laparoscopic hysterectomy. The procedure was performed using a self-developed five-channel port and a vaginal support ring. RESULTS: Hysterectomy and bilateral adnexectomy (or bilateral salpingectomy) in all 30 cases (mean age: 51.43 ± 4.60 years and body mass index: 23.42 ± 1.45 kg/m2 ) were successfully performed completely under transvaginal NOTES. Mean operation time was 95.90 ± 14.60 minutes and mean blood loss during the procedure was 52.50 ± 19.20 mL. Average weight of specimen was 79.97 ± 35.48 g. Only one complication of bladder injury was noted and was rectified accordingly. Visual Analog Score (VAS) at first day after operation was 2.70 ± 0.72. After follow-up for 4.50 ± 1.85 months, all the patients' vaginal stump healed well without scar formation. CONCLUSION: Our study showed that use of multichannel abdominal port could make laparoscopic instruments easier to fix and operate wherein the vaginal support ring reduces the leakage of carbon dioxide pneumoperitoneum. There was no scar on the abdomen and VAS was much lower. This study also demonstrated cosmetic benefits and rapid postoperative recovery.

Feasibility of methane bioconversion to methanol by acid-tolerant ammonia-oxidizing bacteria.

Bioconversion of biogas to value-added liquids has received increasing attention over the years. However, many biological processes are restricted under acidic conditions owing to the excessive carbon dioxide (CO2, 30-40% v/v) in biogas. Here, using an enriched culture dominated by acid-tolerant ammonia-oxidizing bacteria (AOB) 'Candidatus Nitrosoglobus', this study examined the feasibility of producing methanol from methane in the CO2-acidified environment (i.e. pH of 5.0). Within the tested dissolved methane range (0.1-0.9 mM), methane oxidation by the acid-tolerant AOB culture followed first-order kinetics, with the same rate constant (i.e. 0.43 (L/(g VSS‧h)) between pH 7.0 and 5.0. The acidic methane oxidation showed robustness against high dissolved concentrations of CO2 (up to 4.06 mM) and hydrogen sulfide (H2S up to 0.11 mM), which led to a high methanol yield of about 30-40%. As such, the raw biogas containing toxic CO2 and H2S can directly serve for methanol production by this acid-tolerant AOB culture, economizing a conventionally costly biogas upgradation process. Afterwards, two batch reactors fed with methane and oxygen intermittently both obtained a final concentration of 1.5 mM CH3OH (equal to 72 mg chemical oxygen demand/L) in the liquid, suggesting it is a useful carbon source to enhance denitrification in wastewater treatment systems. In addition, ammonia availability was identified to be critical for a higher rate of this AOB-mediated methanol production. Overall, our results for the first time demonstrated the capability of a novel acid-tolerant AOB culture to oxidize methane, and also illustrated the technical feasibility to utilize raw biogas for methanol production at acidic conditions.

Short-term outcomes of pure transvaginal laparoscopic right colectomy: A novel surgery approach based on an Idea, Development, Exploration, Assessment, Long-term framework stage IIa study.

BACKGROUND AND OBJECTIVES: The application of pure natural orifice translumenal endoscopic surgery (NOTES) to intra-abdominal visceral resections remains limited due to the complexity of the dissection. This study aimed to assess the safety and feasibility of laparoscopic right colectomy using a purely transvaginal approach. METHODS: The data of 12 continuous patients with colon neoplasia who underwent transvaginal right colectomy from November 2018 to July 2020 were prospectively collected, and their perioperative events were recorded. RESULTS: The patients' median age was 70.4 years. Four were diagnosed with colon adenoma and eight with adenocarcinoma. The median operative time was 185 min, with a median blood loss of 25 ml. The median time to gas passing was 32.5 h after surgery. The median postoperative hospital stay was 6 days. One operation was converted to hybrid NOTES due to difficulty with the anastomosis, and one was converted to laparoscopic surgery because of vascular injury. Three cases were grades I, II, and III according to the Clavien-Dindo classification. CONCLUSION: Pure NOTES right colectomy using the transvaginal approach is feasible and safe with good short-term outcomes. We recommend this novel technique for highly-selected patients with no more than a D2 dissection performed by experienced colorectal surgeons.

High-Preservation Single-Cell Operation through a Photo-responsive Hydrogel-Nanopipette System.

Single-cell and in situ cell-based operation with nanopipette approach offers a possibility to elucidate the intracellular processes and may aid the improvement of therapy efficiency and precision. We present here a photo-responsive hydrogel-nanopipette hybrid system that can achieve single-cell operation with high spatial/temporal resolution and negligible cell damage. This strategy overcomes long-time obstacles in nanopipette single-cell studies as high electric potential (ca. 1000 mV) or organic solvent is always used during operations, which would inevitably impose disturbance and damage to targeted cells. The light-triggered system promotes a potential-free, non-invasive single-cell injection, resulting in a well-retained cell viability (90 % survival rate). Moreover, the photo-driven injection enables a precisely dose-controllable single-cell drug delivery. Significantly reduced lethal doses of doxorubicin (163-217 fg cell-1 ) are demonstrated in corresponding cell lines.

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

IMPORTANCE: Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program. OBJECTIVE: To evaluate hrHPV testing as a new screening modality for the national program. DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated. INTERVENTIONS: At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. MAIN OUTCOMES AND MEASURES: The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. RESULTS: A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.